Intravenous IgG Reduces Pathogenic Autoantibodies, Serum IL-6 Levels, and Disease Severity in Experimental Bullous Pemphigoid Models.

Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by autoantibodies to COL17. Currently, systemic corticosteroids are used as first-line treatments for BP; alternatively, intravenous administration of high-dose IgG (IVIG) has been shown to be effective for patients with steroid-resistant BP in clinical practice. However, the effect of IVIG on BP has not fully been investigated. To examine the effects and mechanisms of action of IVIG against BP, we performed IVIG experiments using two experimental BP mouse models. One is a passive-transfer BP model that reproduces subepidermal separation in neonatal mice by the passive transfer of IgGs against COL17, such as polyclonal or monoclonal mouse IgG or IgG from BP patients. The other is an active BP model that continuously develops a disease phenotype in adult mice. IVIG decreased pathogenic IgG and the disease scores in both models. Injected IVIG distributed throughout the dermis and the intercellular space of the lower epidermis. Notably, IVIG inhibited the increase of IL-6 in both models, possibly by suppressing the production of IL-6 by keratinocytes. These results suggest that the inhibitory effects of IVIG on BP are associated with the reduction of pathogenic IgG and the modulation of cytokine production.

Effects of gender and body weight on fibroblast growth factor 23 responsiveness to estimated dietary phosphorus.

Fibroblast growth factor 23 (FGF23) is a molecule involved in regulating phosphorus homeostasis. Although some studies indicated an association between serum FGF23 levels and sex, the association has not been fully investigated. The purpose of this study was to evaluate whether sex could influence FGF23 responsiveness to dietary phosphorus intake in healthy individuals. Thirty two healthy subjects between 21 and 28 years were recruited for this study. Subjects performed 24-hour urine collection and blood samples were collected. We estimated phosphorus intake (UC-P) from the urine collection (UC), and evaluated any association between UC-P and serum FGF23 levels. Subsequently, we compared serum FGF23 levels between males and females. Positive correlation was observed between UC-P and serum FGF23 levels. Serum FGF23 levels were significantly higher in males than in females. Serum FGF23 levels/UC-P was significantly higher in females than in males. There was no significant difference in serum FGF23 levels/UC-P/BW between the male and female groups. Our results indicate that there was no gender difference between FGF23 responsiveness to phosphorus intake per body weight.

Nocturnal eating disturbs phosphorus excretion in young subjects: a randomized crossover trial.

BACKGROUND: Nocturnal eating have recently increased. Serum phosphorus levels and regulators of phosphorus have circadian variations, so it is suggested that the timing of eating may be important in controlling serum phosphorus levels. However, there have been no reports on the effects of nocturnal eating on phosphorus metabolism. The objective was to evaluate the effects of nocturnal eating on phosphorus metabolism. METHODS: Fourteen healthy men participated in two experimental protocols with differing dinner times. The design of this study was a crossover study. The subjects were served test meals three times (breakfast; 07:30 h, lunch; 12:30 h, dinner; 17:30 or 22:30 h) a day. Blood and urine samples were collected to assess diurnal variation until the following morning. RESULTS: The following morning, fasting serum phosphorus levels in the late dinner group were markedly higher than those in the early dinner group (p < 0.001), although serum calcium levels were maintained at approximately constant levels throughout the day in both groups. Fluctuations in urinary calcium excretion were synchronized with the timing of dinner eating, however, fluctuations in urinary phosphorus excretion were not synchronized. Urinary phosphorus excretions at night were inhibited in the late dinner group. In the late dinner group, intact parathyroid hormone levels didn't decrease, and they were significantly higher in this group compared with the early dinner group at 20:00 h (p = 0.004). The following morning, fasting serum fibroblast growth factor 23 levels in the late dinner group had not changed, but those in the early dinner group were significantly increased (p = 0.003). Serum free fatty acid levels before dinner were significantly higher in the late dinner group compared with the early dinner group. CONCLUSIONS: Our results indicate that nocturnal eating inhibits phosphorus excretion. It is suggested that nocturnal eating should be abstained from to manage serum phosphorus levels to within an adequate range.

Scalp acupuncture effects of stroke studied with magnetic resonance imaging: different actions in the two stroke model rats.

BACKGROUND: Scalp acupuncture (SA) therapy on strokes has been empirically established and widely used in clinics in China. The evidence from clinical studies suggests that SA produces significant benefits for some patients with stroke. METHODS: The effect of scalp acupuncture was studied using MRI for two different stroke models: spontaneously hypertensive stroke-prone (SHR-SP) rats and rats with transiently induced focal cerebral ischaemia by middle cerebral artery occlusion for 2 h (MCAO rats). RESULTS: Stroke onset in SHR-SP rats was characterised by a development of vasogenic oedema without any appearance of cytotoxic oedema. Scalp acupuncture reduced rapidly neurological dysfunction in SHR-SP rats and reduced the volume of the vasogenic oedema during the same period. In contrast, in MCAO rats, focal cerebral ischaemia caused an immediate development of cytotoxic oedema without any appearance of vasogenic oedema. Vasogenic oedema developed after reperfusion. Scalp acupuncture had no significant effects on the cytotoxic oedema, vasogenic oedema or neurological dysfunction of the MCAO rats within the time span examined. CONCLUSION: Scalp acupuncture had a rapid and strong effect on neurological dysfunction only in the hypertensive stroke-model by reducing the vasogenic oedema. Our results suggest that, if there are similar underlying mechanisms in human strokes, scalp acupuncture may be more beneficial for patients with strokes of hypertension-caused vasogenic origin than ischaemic origin.

Grape seed proanthocyanidins extract promotes bone formation in rat's mandibular condyle.

We studied the effect of dietary supplementation with grape seed proanthocyanidins extract (GSPE) 3 mg added in 100 g high-calcium diet with a calcium content of 1697 mg 100 g(-1) on mandibular condyle bone debility, which was induced by a low-calcium diet. Forty Wistar male rats, 5 week old, were randomly divided into control (Co), low-calcium diet (LC), low-calcium/high-calcium diet (LCH), and low-calcium/high-calcium with supplementary GSPE diet (LCHG) groups for 6 wk. Bone formation of the mandibular condyle was measured using peripheral quantitative computed tomography (pQCT). Significant differences were not seen among the four groups for body weight, measured weekly. The LCHG group scored significantly higher in cortical bone density, total bone cross-sectional area, cortical bone cross-sectional area, cortical bone mineral content, total bone density, total bone mineral content, and in the stress-strain index to the reference axis x when compared with the LCH group. We concluded that a high-calcium diet combined with GSPE supplementation is more effective in reversing mandibular condyle bone debility in rats than is a low-calcium diet, standard diet, or high-calcium diet alone.