Tsikas, D. & Chobanyan, K. Pitfalls in the measurement of tissue DDAH activity: is DDAH sensitive to nitrosative and oxidative stress&quest. Kidney international 74, 969–969 (2008).

(c)      Evaluated the effectiveness of the Company’s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and

As far as C60 as a potent antioxidant, Mark has tried it, I have not, but I did do a self experiment 2 years ago. You are familiar of course with viagra which is a phosphodiesterase inhibitor and thus raises nitric oxide endothelial levels. This increase can also boost exercise endurance. So I took a pretty hefty dose and exercised with it, but then it always gave nasal congestion, headache, and flushing which I tried to eliminate with various high dose antioxidants. None of them worked at any dose except for one. Sangre de Drago is the highest rated antioxidant of any, with a sky high ORAC rating, and is literally blood red. In two minutes all of the nitric oxide effects completely vanished. It never failed.

The testing and approval process requires substantial time, effort and financial resources, and we cannot be certain that any approvals for Aramchol or any future product candidates will be granted on a timely basis, if at all.

It is hard to say, but Liz is an excellent speaker and is always on the road, so I wouldn’t be surprised if they get the funds together to open some clinics. We should know in a year if this is going to happen.

All in all, it was a cordial and friendly meeting that further thawed ice between the two countries. Helping this process is probably the longevity of Abe’s tenure and hold on power. Some believe that he is going for an unprecedented third term in office and has already been re-elected as the leader of the ruling Liberal Democratic Party (one of the longest reigning parties in the world). It helps to have a strong leader in power in order to deal with a powerful strongman like Putin who skirted around the constitution by temporarily stepping down from Prime Minister-ship only to return to power as the President.

Celldex Therapeutics ( NASDAQGM:CLDX ) is an integrated biopharmaceutical company that applies its comprehensive Precision Targeted Immunotherapy Platform to generate a pipeline of candidates to treat cancer and other difficult-to-treat diseases. Celldex’s immunotherapy platform includes a complementary portfolio of monoclonal antibodies, antibody-targeted vaccines and immunomodulators to create novel disease-specific drug candidates.

1. FDA Press Release, “FDA announces voluntary recall of several medicines containing valsartan following detection of an impurity,” fda.gov,  July 17, 2018. 2. FDA Press Release, “FDA Announces Preliminary GC/MS Headspace Method…” August 2018. 3. J. Christensen, "FDA Finds Additional Impurity in Heart Drug," cnn.com, September 15, 2018, https://www.cnn.com/2018/09/13/health/valsartan-recall-additional-impuri… 4. EMA Press Release, “Valsartan: Review of Impurities Extended to Other Sartan Medicines,” ema.europa.eu, September 21, 2018. 5. EDQM Press Release, “OMCLs Release Three Methods for Determination of NDMA in Sartans,”edqm.eu, September 21, 2018. 6.  J. Christensen, “FDA Expands Recall of Blood Pressure Drug", cnn.com, August 10, 2018. 7. C. Purdy, “A Common Blood Pressure Medicine is Being Recalled Because it Was Mixed With NDMA,” qz.com, July 18, 2018. 8. R.G. Liteplo et al., “Concise International Chemical Assessment Document 38: NDMA,” World Health Organization,Geneva, 2002. 9. P. Magee and J. Barnes, “Production of Malignant Primary Hepatic Tumors in the Rat by Feeding NDMA,” British Journal of Cancer, 10(1) pp114-122 (1956). 10. A. Tricker et al., “NItroso Comounds in Cigarette Tobacco and Their Occurrence in Mainstream Tobacco Smoke,” Carcinogenesis 12(2); 257-261 (1991). 11.M. Jagerstad, “Genotoxicity of Heat Processed Foods, Mutation Research 574(1-2), 156-172 (August 2005). 12. Patents Issued to Zhejian Huahai Pharma Co., Ltd, justia.com, www.patents.justia.com/assignee/zhejiang-huahai-pharmaceutical-co-ltd 13. A. Harney, B. Hirschler, “Toxin at the Heart of Drug Recall Shows Holes in Medical Safety Net,” Reuters.com, August 22, 2018, 14. F. Southey, “US FDA Flagged GMP Concerns at Valsartin Manufacturing Plants in Two 483s,” in-pharmatechnologist.com, August 22, 2018.

        In the past, securities class action litigation has often been brought against a company following a decline in the market price of its securities. This risk is especially relevant for biopharmaceutical companies, which have experienced significant stock price volatility in recent years. The results of any legal proceedings are inherently uncertain and, regardless of the ultimate outcome or the merits, require substantial time and other resources to defend. Accordingly, any litigation that we could face may result in substantial costs to us, divert management’s attention and resources from our company as well as harm our reputation with analysts and investors, which could substantially harm our business, financial condition and results of operations.

Zhejiang approved a process change in the manufacture of valsartan API in November 2011, but “failed to adequately assess the potential formation of mutagenic impurities when you implemented the new process,” FDA noted in the letter. The company also failed to evaluate the need for additional analytical methods to detect impurities prior to making the process change.

Any authorization granted by member state authorities, which within three years of its granting is not followed by the actual placing on the market of the authorized product in the authorizing member state, ceases to be valid (Art. 24 (4) and (5) Directive 2001/83/EC). When an authorized product previously placed on the market in the authorizing member state is no longer actually present on the market for a period of three consecutive years, the authorization for that product shall cease to be valid. The same two three year periods apply to authorizations granted by the European Commission based on the centralized procedure (Art. 14 (4) and (5) Regulation (EC) 726/2004).

NASH is an emerging world crisis impacting an estimated 3% to 5% of the U.S. population and an estimated 2% to 4% globally, and is associated with increased risk of liver cirrhosis, liver failure, hepatocellular cancer, as well as metabolic and cardiovascular diseases. The major characteristics of NASH are elevated liver fat, inflammation, ballooning and fibrosis.