Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Apr 2010
Inhibitory effect of fucoidan on nitric oxide production in lipopolysaccharide-activated primary microglia.
1. Microglial activation plays an important role in the pathogenesis of neurodegenerative diseases by producing various pro-inflammatory cytokines. Microglia-derived nitric oxide (NO) is critical for the lipopolysaccharide (LPS)-induced selective loss of dopaminergic neurons. 2. ⋯ Fucoidan (125 microg/mL) also suppressed phosphorylation of p38 and extracellular signal-regulated kinase (ERK) by approximately 50%, but not that of c-Jun N-terminal kinase. 5. The results provide the first evidence that fucoidan has a potent inhibitory effect against LPS-induced NO production by microglia. The results also suggest that this inhibitory action of fucoidan involves suppression of p38 and ERK phosphorylation.
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Clin. Exp. Pharmacol. Physiol. · Apr 2010
Comparative Study4-Phenyl butyric acid does not generally reduce glucose levels in rodent models of diabetes.
1. Endoplasmic reticulum (ER) stress plays a role in the pathogenesis of diabetes. The aim of the present study was to investigate the effect of 4-phenyl butyric acid (PBA), a novel chemical chaperone reducing ER stress, on serum glucose level in different strains of normal and diabetic rodents. 2. 4-Phenyl butyric acid (1 g/kg per day, i.g.) was administered to ob/ob Type 2 diabetic mice, alloxan-induced Type 1 diabetic mice and hydrocortisone (HC)-induced Type 2 diabetic mice as well as normal C57BL/6J mice and Kumming mice for 14 days to evaluate its effect on serum glucose levels. ⋯ Normoglycaemia was obtained in ob/ob mice after 4 days of PBA treatment and was maintained for up to 14 days treatment. 4. 4-Phenyl butyric acid had no glucose-lowering effect in alloxan-induced Type 1 diabetic mice, HC-induced Type 2 diabetic mice and non-obese Type 2 diabetic GK rats. In addition, it had no beneficial effects on insulin resistance in HC-treated mice. 5. 4-Phenyl butyric acid did not affect normal serum glucose levels in C57BL/6 J mice, Kunming mice or WKY rats. 6. In conclusion, PBA does not generally reduce glucose levels in rodent models of diabetes, although it can normalize glucose levels in ob/ob diabetic mice, indicating that restoration of ER function as diabetes therapy is limited to conditions under which ER stress is involved in the high glucose levels.
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Clin. Exp. Pharmacol. Physiol. · Apr 2010
Role of proteinuria in defining pre-eclampsia: clinical outcomes for women and babies.
1. The presence of proteinuria is not essential to the diagnosis of pre-eclampsia under many diagnostic consensus statements. The aim of the present study was to assess maternal and perinatal outcomes after proteinuric pre-eclampsia compared with other non-proteinuric disease presentations. 2. ⋯ Four cases of eclampsia all occurred in non-proteinuric women. The perinatal mortality rate was lower for the offspring of women with proteinuric pre-eclampsia compared with offspring of non-proteinuric women (13/1000 and 31/1000, respectively; P = 0.006). 4. The results of the present study indicate that the presence of proteinuria denotes a group of women who have higher antenatal blood pressure, who deliver at earlier gestation and require operative delivery more commonly, although it is not an indicator of other markers of maternal morbidity or perinatal mortality.