Adverse events related to platelet-rich plasma therapy and future issues to be resolved.

Platelet-rich plasma (PRP) is the portion of plasma with a platelet concentration above baseline that is recovered through centrifugation of autologous blood. PRP therapy is currently used for wound healing and pain relief in diverse medical fields. Although there have been recent reports of adverse events (AEs) possibly related to PRP treatment, the safety profile of PRP treatment remains unclear.

Application to Butterbur Products of a Suggested Daily Intake-Based Safety Evaluation of Individual Herbal Supplements with Cytochrome P450 Expression as a Major Index.

The present paper first proposes a method for ensuring the safety of commercial herbal supplements, termed the suggested daily intake-based safety evaluation (SDI-based safety evaluation). This new method was inspired as a backward analog of the acceptable daily intake (ADI) derivation from the no observed adverse effect level (NOAEL), the basis of food additive risk analysis; namely, rats are dosed with individual herbal supplement products at the SDI for human use multiplied by 100 (the usual uncertainty factor value) per body weight for 8 d. The primary endpoint is the sign of adverse effects on liver, especially gene expression of cytochrome P450 (CYP) isoforms.

Current status of platelet-rich plasma therapy under the act on the safety of regenerative medicine in Japan.

In Japan, a legal framework has been established for the safe and effective application of regenerative medicine. After eight years of the Act on the Safety of Regenerative Medicine (RM Act), discussions have been underway in the Ministry of Health, Labor and Welfare of Japan to revise the law owing to numerous novel technologies and inappropriate case reports not anticipated when the law was enacted. Therefore, in this review article, we have reviewed the regenerative medicine provision plans and the contribution of platelet-rich plasma (PRP) therapy, a regenerative medicine technique widely used in Japan post RM Act implementation, to these plans.

Internalization and Decrease of Duodenal DMT1 Involved in Transient Suppression of Iron Uptake in Short-Acting Mucosal Block.

Mucosal block (MB) is induced by the oral administration of excess iron (10 mg) and suppresses intestinal iron absorption for 3-72 h. The inhibition of iron absorption is accompanied by the downregulation of molecules associated with intestinal iron absorption. Recently, we found that a smaller amount of iron (1 mg) also induced a transient suppression of iron uptake without affecting gene expression levels (short-acting mucosal block, SAMB), which is specific to iron-deficient rats.

Marginally excessive iron loading transiently blocks mucosal iron uptake in iron-deficient rats.

Regular "mucosal block" is characterized by decreased uptake of a normal iron load 3-72 h after the administration of excess iron (generally 10 mg) to iron-deficient animals. We found that short-acting mucosal block could be induced by much lower iron concentration and much shorter induction time than previously reported, without affecting levels of gene expression. A rapid endocytic mechanism was reported to decrease intestinal iron absorption after a high iron load, but the activating iron load and the time to decreased absorption were undetermined.

Rapid regulation of intestinal divalent metal (cation) transporter 1 (DMT1/DCT1) and ferritin mRNA expression in response to excess iron loading in iron-deficient rats.

We determined the effects of excess iron on the expression of duodenal divalent metal transporter 1 (DMT1) and ferritin (Ft) in iron-deficient rats which had increased iron absorption. DMT1 mRNA was down-regulated and Ft mRNA was up-regulated 2 h after administering the iron. However, more than 2 h was needed for Ft protein synthesis to occur in the duodenal mucosa.

High dose of commercial products of kava (Piper methysticum) markedly enhanced hepatic cytochrome P450 1A1 mRNA expression with liver enlargement in rats.

Commercial products containing the kava plant (Piper methysticum), known to have the anxiolytic activity, are banned in several European countries and Canada because of the suspicion of a potential liver toxicity. In some reports, kava and kavalactones (major constituents of kava) inhibited activities of cytochrome P450 (CYP) isoforms including CYP1A2. On the other hand, a few studies showed that administration of kava to rats moderately increased CYP1A2 proteins in the liver.