Publications by authors named "Rejhan Idrizi"

4 Publications

  • Page 1 of 1

Striatal but not frontal cortical up-regulation of the epidermal growth factor receptor in rats exposed to immune activation in utero and cannabinoid treatment in adolescence.

Psychiatry Res 2016 06 18;240:260-264. Epub 2016 Apr 18.

Molecular Psychopharmacology Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia; Northern Psychiatry Research Centre, Northern Area Mental Health Servic(f)e, Epping, Victoria, Australia. Electronic address:

In utero maternal immune activation (MIA) and cannabinoid exposure during adolescence constitute environmental risk factors for schizophrenia. We investigated these risk factors alone and in combination ("two-hit") on epidermal growth factor receptor (EGFR) and neuregulin-1 receptor (ErbB4) levels in the rat brain. EGFR but not ErbB4 receptor protein levels were significantly increased in the nucleus accumbens and striatum of "two-hit" rats only, with no changes seen at the mRNA level. These findings support region specific EGF-system dysregulation as a plausible mechanism in this animal model of schizophrenia pathogenesis.
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June 2016

Effect of oxygen on cardiac differentiation in mouse iPS cells: role of hypoxia inducible factor-1 and Wnt/beta-catenin signaling.

PLoS One 2013 12;8(11):e80280. Epub 2013 Nov 12.

Heart Failure Research Group, Baker IDI Heart and Diabetes Institute, Melbourne, Australia.

Background: Disturbances in oxygen levels have been found to impair cardiac organogenesis. It is known that stem cells and differentiating cells may respond variably to hypoxic conditions, whereby hypoxia may enhance stem cell pluripotency, while differentiation of multiple cell types can be restricted or enhanced under hypoxia. Here we examined whether HIF-1alpha modulated Wnt signaling affected differentiation of iPS cells into beating cardiomyocytes.

Objective: We investigated whether transient and sustained hypoxia affects differentiation of cardiomyocytes derived from murine induced pluripotent stem (iPS) cells, assessed the involvement of HIF-1alpha (hypoxia-inducible factor-1alpha) and the canonical Wnt pathway in this process.

Methods: Embryoid bodies (EBs) derived from iPS cells were differentiated into cardiomyocytes and were exposed either to 24 h normoxia or transient hypoxia followed by a further 13 days of normoxic culture.

Results: At 14 days of differentiation, 59 ± 2% of normoxic EBs were beating, whilst transient hypoxia abolished beating at 14 days and EBs appeared immature. Hypoxia induced a significant increase in Brachyury and islet-1 mRNA expression, together with reduced troponin C expression. Collectively, these data suggest that transient and sustained hypoxia inhibits maturation of differentiating cardiomyocytes. Compared to normoxia, hypoxia increased HIF-1alpha, Wnt target and ligand genes in EBs, as well as accumulation of HIF-1alpha and beta-catenin in nuclear protein extracts, suggesting involvement of the Wnt/beta-catenin pathway.

Conclusion: Hypoxia impairs cardiomyocyte differentiation and activates Wnt signaling in undifferentiated iPS cells. Taken together the study suggests that oxygenation levels play a critical role in cardiomyocyte differentiation and suggest that hypoxia may play a role in early cardiogenesis.
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July 2014

Percutaneous re-circulating isolated limb perfusion of gentamicin in a large animal model: targeted delivery of gentamicin to limb.

Am J Transl Res 2013 21;5(1):47-52. Epub 2013 Jan 21.

Heart Failure Research Group, BakerIDI Heart & Diabetes Institute Melbourne, Victoria, Australia.

Objective: We have developed a percutaneous recirculation system (V-Vascular, V-V) to enable delivery of high levels of antibiotic to the limb in an isolated and targeted manner for the treatment of limb infection.

Background: Chronic and acute limb infections are relatively commonplace in a variety of wound types. Infection can become refractory to existing treatment strategies and can cause complications associated with wound healing, lead to amputation and even death.

Methods: Gentamicin was delivered to the ovine hind limb (4 mg/kg) using the V-V system, a 'closed' recirculatory catheter system that draws blood from the venous system and returns it to the artery via an oxygenator, or via intra-venous (IV) infusion. Samples of muscle, bone and synovial fluid of the limb were collected at 30 and 60 min post administration of gentamicin.

Results: There was a significantly greater concentration of gentamicin observed in the bone and skeletal muscle of limbs receiving the antibiotic via V-V at 30 min post administration compared to IV delivery, (bone V-V 0.05 ± 0.04, I.V 0.004 ± 0.001 mg/L p<0.05; muscle V-V 0.005 ± 0.001, I.V 0.002 ± 0.0005 mg/L p<0.05) and bone and synovial fluid at 60 min post administration (bone V-V 0.06 ± 0.02, I.V 0.005 ± 0.001 mg/L p<0.05; synovial fluid V-V 34.58 ± 14.9, I.V 3.03 ± 0.59 mg/L p<0.05).

Conclusions: These results suggest that the use of percutaneous recirculation is a safe and effective method for delivering a greater concentration of antibiotic to the limb without systemic implications.
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February 2013

Host rather than graft origin of Matrigel-induced adipose tissue in the murine tissue-engineering chamber.

Tissue Eng 2007 Sep;13(9):2291-300

Bernard Brien Institute for Microsurgery, Melbourne, Victoria, Australia.

We have recently shown that Matrigel-filled chambers containing fibroblast growth factor-2 (FGF2) and placed around an epigastric pedicle in the mouse were highly adipogenic. Contact of this construct with pre-existing tissue or a free adipose graft was required. To further investigate the mechanisms underpinning formation of new adipose tissue, we seeded these chambers with human adipose biopsies and human adipose-derived cell populations in severe combined immunodeficient mice and assessed the origin of the resultant adipose tissue after 6 weeks using species-specific probes. The tissues were negative for human-specific vimentin labeling, suggesting that the fat originates from the murine host rather than the human graft. This was supported by the strong presence of mouse-specific Cot-1 deoxyribonucleic acid labeling, and the absence of human Cot-1 labeling in the new fat. Even chambers seeded with FGF2/Matrigel containing cultured human stromal-vascular fraction (SVF) labeled strongly only for human vimentin in cells that did not have a mature adipocyte phenotype; the newly formed fat tissue was negative for human vimentin. These findings indicate that grafts placed in the chamber have an inductive function for neo-adipogenesis, rather than supplying adipocyte-precursor cells to generate the new fat tissue, and preliminary observations implicate the SVF in producing inductive factors. This surprising finding opens the door for refinement of current adipose tissue-engineering approaches.
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September 2007