Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effects of conventional and a novel colonic-release bile acid sequestrant, A3384, on fibroblast growth factor 19 and bile acid metabolism in healthy volunteers and patients with bile acid diarrhoea

Background: Primary bile acid diarrhoea (BAD) is associated with increased bile acid synthesis and low fibroblast growth factor 19 (FGF19). Bile acid sequestrants are used as therapy, but are poorly tolerated and may exacerbate FGF19 deficiency. Aim: The purpose of this study was to evaluate the pharmacological effects of conventional sequestrants and a colonic-release formulation preparation of colestyramine (A3384) on bile acid metabolism and bowel function in patients with BAD. Methods: Patients with seven-day 75selenium-homocholic acid taurine (SeHCAT) scan retention <10% were randomised in a double-blind protocol to two weeks treatment with twice-daily A3384 250 mg (n = 6), 1 g (n = 7) or placebo (n = 6). Thirteen patients were taking conventional sequestrants at the start of the study. Symptoms were recorded and serum FGF19 and 7α-hydroxy-4-cholesten-3-one (C4) measured. Results: Median serum FGF19 on conventional sequestrant treatment was 28% lower than baseline values in BAD (p < 0.05). C4 on conventional sequestrant treatment was 58% higher in BAD (p < 0.001). No changes were seen on starting or withdrawing A3384. A3384 improved diarrhoeal symptoms, with a median reduction of 2.2 points on a 0–10 Likert scale compared to placebo, p < 0.05. Conclusions: Serum FGF19 was suppressed and bile acid production up-regulated on conventional bile acid sequestrants, but not with A3384. This colonic-release formulation of colestyramine produced symptomatic benefit in patients with BAD

Internationalization of Traditional/Complementary Medicine products: market entry as medicine

Abstract Internationalization of Traditional/Complementary Medicine (T&CM) products is important for initiating and sustaining developments in this field. Particularly for traditional Chinese medicines (TCMs), the global market continues to expand due to an interest in the potential clinical benefits of traditional approaches that are largely considered lower risk and lower cost than many conventional treatments. While the benefits of internationalization hold clear advantages for the business of T&CM products, keeping abreast of regulatory processes in different countries and regions that regularly revise market entry requirements is challenging. At present, the regulations of T&CM products are country specific and largely based on a risk-based assessment with a focus on protecting the consumer. To date, systematic analysis of these regulatory differences between countries and regions is limited. Publically available information about the legal requirements for the market entry of T&CM products were obtained from the relevant regulatory authority’s websites for selected countries and regions (Macau-China, Hong Kong-China, Singapore, Australia, Canada, the European countries and the US). The market entry requirements in terms of quality, safety and efficacy of T&CM products for each country were analyzed and compared. Major differences were identified in the classification of T&CM products, market entry pathways, requirements of compliance with Good Manufacturing Practices; and level of evidence to demonstrate safety and efficacy based on historical use, non-clinical and clinical studies. Variations in the evaluation standards adopted by regulatory authorities pose a number of barriers and opportunities for the internationalization of T&CM products and have great implications for internationalization of TCMs from the sponsors’ and the regulators’ perspectives