Treatment of Fabry patients > 18 years with enzyme supplementation therapy: comparison of efficacy and toxicity of low dose (0,2 mg/kg) fabrazyme (agalsidase beta) or replagal (agalsidase alfa).

Start Date06 May 2002

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100 Clinical Results associated with Agalsidase Beta(Nipro ES Pharma)

100 Translational Medicine associated with Agalsidase Beta(Nipro ES Pharma)

100 Patents (Medical) associated with Agalsidase Beta(Nipro ES Pharma)

Literatures (Medical) associated with Agalsidase Beta(Nipro ES Pharma)

01 Dec 2009·Journal of Cellular PhysiologyQ2 · BIOLOGY

Both B1R and B2R act as intermediate signaling molecules in high glucose‐induced stimulation of glutamate uptake in ARPE cells

Q2 · BIOLOGY

Article

Author: Ho Jae Han ; Kye Yeop Kim ; Soo Hyun Park ; Seul Ki Lim

AbstractBradykinin (BK) is a potent modulator of biological processes in the retina, and retinal pigment epithelial cells (RPE) and the regulation of glutamate are believed to be important in the pathogenesis of diabetic retinopathy. However, the mechanism by which BK regulates glutamate uptake in RPE cells in diabetic retinopathy is unknown. Here, we examined the involvement of BK receptors in high glucose‐induced dysfunction of glutamate uptake in human ARPE cells. High glucose stimulated glutamate uptake and the expression of excitatory amino acid transporter‐4 (EAAT4) mRNA, and these were blocked by treatment with small interfering RNA (siRNA) for BK1 receptor (B1R) and BK2 receptor (B2R), but not scrambled siRNA, supporting an involvement of B1R and B2R in this process. High glucose‐stimulated glutamate uptake was also blocked by the B1R antagonist [des‐Arg10]‐HOE 140 and the B2R antagonist HOE 140. High glucose increased B1R and B2R mRNA and protein expression in a time‐dependent manner, increased B1R and B2R translocation from the cytosol to the nucleus, and stimulated kininogen, kallikrein, and kininase I mRNA expression. We examined whether BK receptors were involved in high glucose‐induced signaling pathways. High glucose stimulated arachidonic acid release, cytosolic phospholipase A2 and cyclooxygenase‐2 proteins, nuclear factor‐κB activation, and inhibitor‐κB activation; these events were blocked by treatment with B1R and B2R siRNAs, but not scrambled siRNA. In addition, high glucose‐induced stimulation of glutamate uptake was blocked by the cyclooxygenase‐2 inhibitors arachidonyl trifluoromethyl ketone, mepacrine, 5‐bromo‐2‐(4‐fluorophenyl)‐3‐[4‐(methyl‐sulfonyl)phenyl]‐thiophene, and N‐[2‐cyclohexyloxy‐4‐nitrophenyl] methane‐sulfonamide, and by the nuclear factor‐κB inhibitors pyrrolidine dithiocarbamate and SN‐50. J. Cell. Physiol. 221: 677–687, 2009. © 2009 Wiley‐Liss, Inc.

01 Jan 2009·European Journal of Clinical InvestigationQ3 · MEDICINE

Proinflammatory cytokine and ligands modulate cardiac peroxisome proliferator‐activated receptors

Q3 · MEDICINE

Article

Author: Y. C. Chen ; Y. H. Kao ; Y. J. Chen ; T. I. Lee

ABSTRACTBackground Peroxisome proliferator‐activated receptors (PPAR) mediate inflammatory processes and alter cardiac function. However, it is not clear whether inflammatory cytokines or PPAR ligands regulate PPARs in the cardiomyocytes to modulate cardiac functions. We investigated the effects of tumour necrosis factor‐alpha (TNF‐α) and PPAR ligands on the expression of PPARs in HL‐1 cardiomyocytes.Materials and methods HL‐1 cardiomyocytes were incubated with and without TNF‐α (1, 10, 25 and 50 ng mL−1) or PPAR ligands (rosiglitazone, pioglitazone and fenofibrate) at concentrations of 0·1, 1 and 10 µm for 24 h. The cells also received SN‐50 (NF‐κB inhibitor, 50 µg mL−1), ascorbic acid (100 µm) and coenzyme Q10 (10 µm) alone or combined with TNF‐α.Results Using reverse transcriptase–polymerase chain reaction and Western blot, we found that incubation of TNF‐α (50 ng mL−1) for 24 h decreased PPAR‐α, but increased PPAR‐γ without altering PPAR‐δ. These effects were not changed by co‐administration of SN‐50. However, co‐administration of ascorbic acid prevented the effect of TNF‐α both on PPAR‐α and PPAR‐γ. Coenzyme Q10 partially attenuated the effect of TNF‐α on PPAR‐γ but did not alter its effect on PPAR‐α. The administration of rosiglitazone (10 µm) and pioglitazone (10 µm) for 24 h increased PPAR‐γ mRNA, but did not alter PPAR‐α or PPAR‐δ. Moreover, fenofibrate (0·1, 1 and 10 µm) increased PPAR‐γ without any effects on PPAR‐α or PPAR‐δ.Conclusions Oxidative stress causes the regulations of PPAR‐α and PPAR‐γ in the TNF‐α‐treated cardiomyocytes. The up‐regulation of PPAR‐γ by PPAR ligands may contribute to their anti‐inflammation effects.

01 Sep 2008·Journal of NeurochemistryQ2 · MEDICINE

NFκB in the mechanism of ammonia‐induced astrocyte swelling in culture

Q2 · MEDICINE

Article

Author: Michael D Norenberg ; Arumugam R Jayakumar ; Mitsuaki Moriyama ; Kiran S Panickar ; Anne P Sinke ; Pichili V B Reddy

AbstractAstrocyte swelling and brain edema are major neuropathological findings in the acute form of hepatic encephalopathy (fulminant hepatic failure), and substantial evidence supports the view that elevated brain ammonia level is an important etiological factor in this condition. Although the mechanism by which ammonia brings about astrocyte swelling remains to be determined, oxidative/nitrosative stress and mitogen‐activated protein kinases (MAPKs) have been considered as important elements in this process. One factor known to be activated by both oxidative stress and MAPKs is nuclear factor κB (NFκB), a transcription factor that activates many genes, including inducible nitric oxide synthase (iNOS). As the product of iNOS, nitric oxide (NO), is known to cause astrocyte swelling, we examined the potential involvement of NFκB in ammonia‐induced astrocyte swelling. Western blot analysis of cultured astrocytes showed a significant increase in NFκB nuclear translocation (a measure of NFκB activation) from 12 h to 2 days after treatment with NH4Cl (5 mM). Cultures treated with anti‐oxidants, including superoxide dismutase, catalase, and vitamin E as well as the MAPKs inhibitors, SB239063 (an inhibitor of p38‐MAPK) and SP600125 (an inhibitor of c‐Jun N‐terminal kinase), significantly diminished NFκB activation by ammonia, supporting a role of oxidative stress and MAPKs in NFκB activation. The activation of NFκB was associated with increased iNOS protein expression and NO generation, and these changes were blocked by BAY 11–7082, an inhibitor of NFκB. Additionally, ammonia‐induced astrocyte swelling was inhibited by the NFκB inhibitors, BAY 11–7082 and SN‐50, thereby implicating NFκB in the mechanism of astrocyte swelling. Our studies indicate that cultured astrocytes exposed to ammonia display NFκB activation, which is likely to be a consequence of oxidative stress and activation of MAPKs. NFκB activation appears to contribute to the mechanism of ammonia‐induced astrocyte swelling, apparently through its up‐regulation of iNOS protein expression and the subsequent generation of NO.

100 Deals associated with Agalsidase Beta(Nipro ES Pharma)

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Indication	Country/Location	Organization	Date
Lactose Intolerance	JP	Nipro ES Pharma KK	25 Sep 2008

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