[Information quality and health risks in Spanish-language retail websites for Chinese herbal medicine]. / Medicina herbal china ofertada en páginas web en español: calidad de la información y riesgos.

OBJECTIVE: The growing use of purchase online via Internet retailers favours the access to potentially toxic natural products. It also contributes to the quick dissemination of the claims made by the retailers on efficacy and safety, these claims being not always based upon reliable information. Here, we have conducted an online search to find Spanish-language retail websites for Chinese herbal medicine and we have analysed them for the quality of product information and the potential health risks. METHODS: i) Online search in Google España to find Spanish-language retail websites for Chinese herbal medicine in which we analysed both the claims regarding possible health benefits and adequate safe use indications ii) Identification of potentially toxic herbs in the websites iii) Quantification of Chinese herbal medicines withdrawn by the Agencia Española de Medicamentos y Productos Sanitarios (AEMPS). RESULTS: 1) Only one third of the 30 Spanish-language retail websites found which sell Chinese herbal medicine observe the law, given that the other websites include illegal Western disease claims as marketing tools, 2) Five websites provide some safety information, 3) Two websites offer potentially toxic herbs and 4) Chinese herbal medicine adulterated with sibutramine, silfenafil or their analogues make a considerable percentage of the total products withdrawn by the AEMPS. CONCLUSION: Online health seekers should be warned about misinformation on retail websites for Chinese herbal medicine and directed to a Spanish government Web site for guidance in safely navigating the Internet for buying Chinese herbal medicine.

The effect of the European traditional use directive on the register of herbal medicinal products in Spain.

BACKGROUND: Directive 2004/24/EC, which came into force in 2011, created new regulatory requirements for traditional herbal medicines (THM). This study compared the Spanish THM registry before and after the Directive came fully into force in 2011. METHODS: We consulted the herbal medicinal plant and drug catalogues (General Council of the Official Colleges of Pharmacists), the website of the European Medicines Agency (EMA), and retail web sites. RESULTS: Of 315 THM (from 39 companies) licensed in Spain in 2010, only 48 (10 companies) remained licensed in 2013, mainly due to their withdrawal: the EMA had received just 123 applications from Spain and at least 34% formerly licensed THM had shifted to the less strictly regulated food sector, while up to 54% might have disappeared from the market. However, there is still a significant presence of retail websites making illegal health claims. CONCLUSION: In Spain, the public health benefits of the Directive 2004/24/EC might be less than expected.

Microparticles released by vascular endothelial cells increase hypoxia inducible factor expression in human proximal tubular HK-2 cells.

Microparticles are produced by vesiculation of the cell plasma membrane and serve as vectors of cell-to-cell communication. Co-culture experiments have shown that hypoxia-inducible factor-α (HIF-α)-regulated-genes are up-regulated in human renal proximal tubular HK-2 cells by endothelial cell factors which might be transported inside endothelial microparticles (EMP). Here we aimed to study in HK-2 cells the effect of EMP, produced by activated endothelial cells, on HIF-α and HIF-α-regulated vascular endothelial growth factor-A (VEGF-A). EMP, at a concentration much lower than that found in plasma, increased the expression of HIF-α/VEGF-A in a COX-2/EP2 receptor dependent manner. Since the EMP/cells ratio was ∼1/1000, we hypothesized that paracrine mediators produced by HK-2 cells amplified the initial signal. This hypothesis was confirmed by two facts which also suggested that the mediators were conveyed by particles released by HK-2 cells: (i) HIF-α was up-regulated in HK-2 cells treated with the pellet obtained from the conditioned medium of the EMP-treated HK-2 cells. (ii) In transwell experiments, EMP-treated cells increased the expression of HIF-α in untreated HK-2 cells. Interestingly, we detected these cells, particles that were released by EMP-treated HK-2 cells. Depending on the pathological context, activation of HIF-α and VEGF-A signaling in renal tissue/cells may have either beneficial or harmful effects. Therefore, our results suggest that their presence in the urinary space of EMP produced by activated endothelial cells may influence the outcome of a number of renal diseases.

MEDLINE-based assessment of animal studies on Chinese herbal medicine.

UNLABELLED: ETHNO-PHARMACOLOGICAL RELEVANCE: The scientific proof and clinical validation of Chinese herbal medicine (CHM) require a rigorous approach that includes chemical standardization, biological assays, animal studies and clinical trials. AIM OF THE STUDY: To assess the experimental design of animal studies on the activity of CHM by selection and scrutinizing of a series of papers in some major disease areas. MATERIALS AND METHODS: We have analyzed the English publications reported in MEDLINE (ISI web of knowledge). RESULTS: Our data showed that (i) research of CHM during the last 10 years had been highly intensified and become more accessible worldwide through increased publications in English, although still most authors had Chinese names; (ii) English journals publishing animal research of CHM were comparable to those publishing animal studies of non-Chinese phytotherapy in terms of impact factor; and (iii) published data on authentication and quality control of CHM, as well as research design of animal studies were far from sufficient to meet the criteria needed to support their reproducibility and reliability. CONCLUSIONS AND PERSPECTIVES: The recent decade witnessed an increase in CHM research activities and CHM English publications. Based on common problems identified in publications on CHM animal studies, we have proposed a checklist that could help in preliminary selection of publications lacking the most common problems and thus would be useful for a quick search of reproducible CHM regimens that are likely to be effective in a given context. The second application of this checklist is to help avoid the most common problems when designing experiments.

Mutual regulation of hypoxic and retinoic acid related signalling in tubular proximal cells.

Hypoxia-inducible factor-1α (HIF-1α) and all-trans retinoic acid (ATRA) afford protection in several experimental models of kidney disease. HIF-1α protein is degraded under normoxia but stabilized by hypoxia, which activates its transcription factor function. ATRA activates another set of transcription factors, the retinoic acid receptors (RAR) α, ß and γ, which mediate its effects on target genes. ATRA also up-regulates the expression of RAR α, ß and γ at the transcriptional level. Here we demonstrate the presence of mutual regulation of hypoxic and retinoic acid related signalling in tubular proximal cells. In human proximal tubular HK-2 cells we have found that: (i) ATRA treatment induces HIF-1α under normoxic conditions and also synergizes with hypoxia leading to the over-expression of HIF-1α and vascular endothelial growth factor-A, a HIF-1α-regulated renal protector. ATRA-induced HIF-1α expression involved stabilization of HIF-1α mRNA but not of HIF-1α protein. (ii) Expression of HIF-1α is an absolute requirement for the transcriptional up-regulation of RARß by ATRA. Transfection with HIF-1α siRNA abolished the induction by ATRA of the expression of both RARß mRNA and protein while treatment with HIF-1α inhibitor YC-1 results in the abolishment of ATRA-induced activity of a retinoic acid-response element (RARE) construct from the RARß promoter. (iii) Hypoxia up-regulates RARß through HIF-1α since this effect was inhibited by HIF-1α knockdown. In contrast to ATRA-induced RARß up-regulation, induction of RARß expression by ATRA did not involve transcriptional up-regulation as hypoxia did not increase the expression of RARß mRNA or the activity of the RARE construct. These results suggest the presence of crosstalk between hypoxia/HIF-1α and ATRA/RARß that may be physiologically and pharmacologically relevant.

All-trans retinoic acid and glycated albumin reciprocally influence their effects in human mesangial cells.

UNLABELLED: All-trans-retinoic acid (tRA) modulates in human mesangial cells (MC) antioxidant defenses, the expression of interleukin-1beta-induced vascular cell-adhesion molecule-1 (VCAM-1), cyclooxygenase-2 (COX-2), and the retinoic acid-receptor-beta (RAR-beta). The correlation of the serum levels of glycated hemoglobin A1c with tRA in type 2 diabetes mellitus patients led us to hypothesize that tRA and glycated albumin (GA), the main circulating glycated protein, might mutually interact in MC. We studied 1) the influence of tRA on GA effects in cultured MC: an assessment was made on how pre-incubation with tRA modified the effects of GA on intracellular oxidation and on the expression of mRNA and protein of COX-2 and VCAM-1; and 2) the influence of GA on tRA effects in MC: we studied how the induction of RARbeta expression by tRA was modified by GA. RESULTS: GA dose-dependently increased intracellular oxidation and the expression of the molecules involved in leukocyte infiltration, namely COX-2 and VCAM-1 . Pre-incubation with tRA exacerbated GA effects by up to a three- to four-fold additional increase. In turn, induction by tRA of RAR-beta was fully inhibited by GA. Thus tRA and GA reciprocally influence their effects in MC. It is possible that this interaction may have a pathophysiological or pharmacological role in diabetic nephropathy.