A comparison between the effects of ochratoxin A and aristolochic acid on the inflammation and oxidative stress in the liver and kidney of weanling piglets

Naunyn-Schmiedeberg's Archives of Pharmacology - Ochratoxin A (OTA) and aristolochic acid (AA) are toxins that can frequently contaminate cereals and cereals-based products. The present study...     

Saroclazines A–C,thio-diketopiperazines from mangrove-derived fungi <Emphasis Type="Italic">Sarocladium kiliense</Emphasis> HDN11-84

Three new diketopiperazine derivatives (DKPs), saroclazines A–C (1–3) along with three known DKPs (4–6) were isolated from mangrove-derived fungi Sarocladium kiliense HDN11-84. Saroclazines A–B (1 and 2) possessed a free amide structure, which was first found in sulfur-containing aromatic DKPs. Their structures were elucidated by NMR, HRESIMS and X-ray. The cytotoxic activity of new compounds (1–3) was tested against HeLa cell lines, among which compound 2 showed an IC₅₀ value of 4.2 µM.     

Clinical and other specialty services offered by pharmacists in the community: the international arena and Israel

The community pharmacy setting is a venue that is readily accessible to the public. In addition, it is staffed by a pharmacist, who is a healthcare provider, trained and capable of delivering comprehensive pharmaceutical care. As such, community pharmacists have a colossal opportunity to serve as key contributors to patients’ health by ensuring appropriate use of medications, preventing medication misadventures, identifying drug-therapy needs, as well as by being involved in disease management, screening, and prevention programs. This unique position gives the pharmacist the privilege and duty to serve patients in roles other than solely that of the stereotypical drug dispenser.Worldwide, as well as in Israel, pharmacists already offer a variety of pharmaceutical services and tend to patients’ and the healthcare system’s needs. This article provides examples of professional, clinical or other specialty services offered by community pharmacists around the world and in Israel and describes these interventions as well as the evidence for their efficacy. Examples of such activities which were recently introduced to the Israeli pharmacy landscape due to legislative changes which expanded the pharmacist’s scope of practice include emergency supply of medications, pharmacists prescribing, and influenza vaccination. Despite the progress already made, further expansion of these opportunities is warranted but challenging. Independent prescribing, as practiced in the United Kingdom or collaborative drug therapy management programs, as practiced in the United States, expansion of vaccination programs, or wide-spread recognition and reimbursement for medication therapy management (MTM) programs are unrealized opportunities. Obstacles such as time constraints, lack of financial incentives, inadequate facilities and technology, and lack of professional buy-in, and suggested means for overcoming these challenges are also discussed.     

Improving research and policy interactions requires a better understanding of what works in different contexts

There is keen interest in many jurisdictions in finding ways to improve the way that research evidence informs policy. One possible mechanism for this is to embed academics within government agencies either as advisers or full staff members. Our commentary argues that, in addition to considering the role of academics in government as proposed by Glied and colleagues, we need to understand better how research and policy interactions function across policy sectors. We believe more comparative research is needed to understand if and why academics from certain disciplines are more likely to be recruited to work in some policy sectors rather than others. We caution against treating government as monolithic by advocating the same model for collaborative interaction between academics and government. Lastly, we contend that contextualized research is needed to illuminate important drivers of research and policy interactions before we can recommend what is likely to be more and less effective in different policy sectors.     

A neo-institutional analysis of the hidden interaction between the Israeli Supreme Court and the Ministry of Finance: the right to healthcare services

Background

Under structural conditions of non-governability, most players in the policy arena in Israel turn to two main channels that have proven effective in promoting the policies they seek: the submission of petitions to the High Court of Justice and making legislative amendments through the Economic Arrangements Law initiated by the Ministry of Finance. Nevertheless, an analysis of the principal trends emerging from the High Court of Justice rulings and legislative amendments through the Economic Arrangements Law indicates that these channels are open to influence, primarily by forces that are essentially neo-liberal. Little is known about the effects of these trends on the right to healthcare services, which in Israel has not been legislated as an independent constitutional law in Basic Laws.

Methods

We use four major legal cases decided by the Supreme Court of Israel in the past 10 years where the Court reviewed new legislative initiatives proposed by the Economic Arrangements Law in the area of healthcare. We utilize an institutional approach in our analysis.

Results

A neo-institutional analysis of the legal cases demonstrates that petitions against the Economic Arrangements Law in the area of healthcare services have been denied, even though the Court uses strong rhetoric against that law and the government more generally in addressing issues that concern access to healthcare services and reforms in the healthcare system. This move strengthens the trend toward a neo-liberal public policy and significantly weakens the legal protection of the right to healthcare services.

Conclusion

In deciding petitions against the Economic Arrangements Law in the area of healthcare, the Supreme Court allows the Ministry of Finance to be a dominant player in the formation of public policy. In doing so, it may be promoting a goal of strengthening its position as a political institution that aspires to increase the public’s trust in the judiciary and especially in the Supreme Court itself, in addition to exercising judicial restraint and allowing more leeway to the executive and legislative branches more generally.

     

Evaluation of Hydrogen Exchange Mass Spectrometry as a Stability-Indicating Method for Formulation Excipient Screening for an IgG4 Monoclonal Antibody

Antibodies are molecules that exhibit diverse conformational changes on different timescales, and there is ongoing interest to better understand the relationship between antibody conformational dynamics and storage stability. Physical stability data for an IgG4 monoclonal antibody (mAb-D) were gathered through traditional forced degradation (temperature and stirring stresses) and accelerated stability studies, in the presence of different additives and solution conditions, as measured by differential scanning calorimetry, size exclusion chromatography, and microflow imaging. The results were correlated with hydrogen exchange mass spectrometry (HX-MS) data gathered for mAb-D in the same formulations. Certain parameters of the HX-MS data, including hydrogen exchange in specific peptide segments in the C_H2 domain, were found to correlate with stabilization and destabilization of additives on mAb-D during thermal stress. No such correlations between mAb physical stability and HX-MS readouts were observed under agitation stress. These results demonstrate that HX-MS can be set up as a streamlined methodology (using minimal material and focusing on key peptide segments at key time points) to screen excipients for their ability to physically stabilize mAbs. However, useful correlations between HX-MS and either accelerated or real-time stability studies will be dependent on a particular mAb's degradation pathway(s) and the type of stresses used.     

Prediction of Human Brain Penetration of P-glycoprotein and Breast Cancer Resistance Protein Substrates Using In Vitro Transporter Studies and Animal Models

Four P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrates with human cerebrospinal fluid (CSF) concentrations and preclinical neuropharmacokinetics were used to assess in vitro–in vivo extrapolation of brain penetration in preclinical species and the ability to predict human brain penetration. Unbound brain (C_b,u), unbound plasma (C_p,u), and CSF compound concentrations (C_CSF) were measured in rats and nonhuman primates (NHPs), and the unbound partition coefficients (C_b,u/C_p,u and C_CSF/C_p,u) were used to assess brain penetration. The results indicated that for P-gp and BCRP dual substrates, brain penetration was severally impaired in all species. In comparison, for P-gp substrates that are weak or non-BCRP substrates, improved brain penetration was observed in NHPs and humans than in rats. Overall, NHP appears to be more predictive of human brain penetration for P-gp substrates with weak or no interaction with BCRP than rat. Although C_CSF does not quantitatively correspond to C_b,u for efflux transporter substrates, it is mostly within 3-fold higher of C_b,u in rat and NHP, suggesting that C_CSF can be used as a surrogate for C_b,u. Taken together, a holistic approach including both in vitro transporter and in vivo neuropharmacokinetics data enables a better estimation of human brain penetration of P-gp/BCRP substrates.