The impact of statin therapy on plasma asymmetric dimethylarginine (ADMA) levels has not been conclusively studied. Therefore the aim of the meta-analysis was to assess the effect of statins on circulating ADMA levels. We searched selected databases (up to August 2014) to identify randomized controlled trials (RCTs) that investigate the effect of statins on plasma ADMA concentrations. A weighted meta-regression (WMD) using unrestricted maximum likelihood model was performed to assess the impact of statin dose, duration of statin therapy and baseline ADMA concentrations as potential variables on the WMD between statin and placebo group. In total, 1134 participants in 9 selected RCTs were randomized; 568 were allocated to statin treatment and 566 were controls. There was a significant reduction in plasma ADMA concentrations following statin therapy compared with placebo (WMD: − 0.104 μM, 95% confidence interval: − 0.131 to − 0.077, Z = − 7.577, p < 0.0001). Subgroups analysis has shown a significant impact of hydrophilic statins (WMD: − 0.207 μM, 95%CI: − 0.427 to + 0.013, Z = − 7.250, p < .0001) and a non-significant effect of hydrophobic statins (WMD: − 0.101 μM, 95%CI: − 0.128 to − 0.074, Z = − 1.845, p = 0.065). In conclusion, this meta-analysis of available RCTs showed a significant reduction in plasma ADMA concentrations following therapy with hydrophilic statins.

Kielstein, A., Tsikas, D., Galloway, G. P. & Mendelson, J. E. Asymmetric dimethylarginine (ADMA)—A modulator of nociception in opiate tolerance and addiction?Nitric oxide: biology and chemistry/official journal of the Nitric Oxide Society 17, 55–59 (2007).

Schwarz, E. C., Qu, B. & Hoth, M. Calcium, cancer and killing: the role of calcium in killing cancer cells by cytotoxic T lymphocytes and natural killer cells. Biochim. Biophys. Acta. 1833, 1603–1611 (2013).

Diamedica Inc. ( TSX:DMA.V ) is a biopharmaceutical company that has developed novel therapeutic compounds aimed to improve the lives of patients with diabetes and other major, medical-unmet diseases. DiaMedica’s lead compound, DM-199, represents a novel approach to treating Type 1 and Type 2 diabetes by demonstrating significant results against three major aspects of these diseases: 1) halting the autoimmune attack on beta cells; 2) proliferating insulin producing beta cells; and 3) improving glucose control. Treatment with DiaMedica’s monoclonal antibody, DM-204, has demonstrated significant improvement in glucose control, blood pressure and cholesterol levels in in vivo models of Type 2 diabetes.

We rely, and expect to continue to rely, on third parties for the production of clinical and commercial quantities of Aramchol. Future FDA and state inspections may identify compliance issues at the facilities of our contract manufacturers that may disrupt production or distribution, or require substantial resources to correct.

Our net loss for the year ended December 31, 2018 was approximately $9.9 million, representing a decrease of approximately $2.4 million, or approximately 20%, compared to approximately $12.3 million for the year ended December 31, 2017. The decrease primarily resulted from the above-mentioned decrease in research and development expenses and as well the increase in revenues due to the milestone payment received from Samil.

24–30 h post-transfection, cells were washed thrice with PBS and scraped into Na2CO3 pH 11 and left on ice for 20 min. The solution was sonicated thrice for 20 sec bursts. By adding an equal volume of 90% sucrose/MES/NaCl-Buffer, the solution was adjusted to 45% sucrose density. Layers of 35% and 5% sucrose were then cautiously added on top of the lysate. All samples were centrifuged at 273,000 g for 16 hours at 4 °C (SW60 rotor, Beckman Instruments, Palo Alto, CA). 12 fractions of equal volumes (1 mL) were collected and their protein content quantified by Nanodrop. The content of cholesterol for each fraction was assayed by the Amplex Red Assay (Life Technologies, Carlsbad, CA) according to the manufacturer’s instructions. Notably, low-density fractions 1–3 usually contain little to no protein, and therefore these samples were excluded from use during further experiments.

Under the Companies Law, and the Securities Law, 5738—1968, or the Securities Law, a company may indemnify, or undertake in advance to indemnify, an Office Holder for the following liabilities and expenses, imposed on Office Holder or incurred by Office Holder due to acts performed by him or her as an Office Holder, provided its articles of association include a provision authorizing such indemnification:

        Operating segments are defined as components of an enterprise for which separate financial information is available for evaluation by the chief operating decision maker in deciding how to allocate resources and in assessing performance. The Company operates in one operating segment, the business of developing peptide-based drugs for a variety of therapeutic uses.

I am trying to solve the issues at hand, and finding out what the best approach is , and the only way to do that is to look at the studies/evidence.

        We have never commercialized a product, and even if one of our product candidates is approved by the appropriate regulatory authorities for marketing and sale, it may nonetheless fail to gain sufficient market acceptance by physicians, patients, third-party payors and others in the medical community. Physicians are often reluctant to switch their patients from existing therapies even when new and potentially more effective or convenient treatments enter the market. Further, patients often acclimate to the therapy that they are currently taking and do not want to switch unless their physicians recommend switching products or they are required to switch therapies. Even if we are able to obtain marketing approval of zilucoplan for the treatment of complement mediated diseases, physicians and patients may decide not to switch to zilucoplan. In addition, even if we are able to demonstrate our product candidates’ safety and efficacy to the FDA and other regulators, safety concerns in the medical community may hinder market acceptance.

Li, J. et al. Inhibition of p38 mitogen-activated protein kinase and transforming growth factor-beta1/Smad signaling pathways modulates the development of fibrosis in adriamycin-induced nephropathy. The American journal of pathology. 169, 1527–1540 (2006).