Search

Many doubts have been expressed about the capacity of states to administer federally supported social service programs. This article relies on institutional theory, punctuated equilibrium theory, and evidence from two states to analyze the way states administer the programs in times of fiscal crisis. The particular context is the fiscal crisis of the early 2000s in substance abuse programs. The analysis suggest that, during the crisis, state administrative authorities and the providers they funded refocused services on federal rather than local priorities. The states and providers also further integrated substance abuse services with the services of other programs and promoted managerial practices that seemed to loosen the match between services and clients. The findings point to some of the ways in which the states’ capacities to respond to crises can be undermined by the national trend toward encouraging state discretion. Findings also reveal challenges for state-level crisis management.

Autotaxin is an extracellular phospholipase D that catalyzes the hydrolysis of lysophosphatidyl choline (LPC) to bioactive lipid lysophosphatidic acid (LPA). LPA has been implicated in many pathological processes relevant to cancer, including cell migration and invasion, proliferation, and survival. The most potent autotaxin inhibitor described to date is the LPA analogue S32826 (IC50 5.6 nM). S32826 and many other autotaxin inhibitors are notably lipophilic, creating a need to improve their physical properties. Polymers are becoming an increasingly useful tool in the delivery of drugs and have the potential to improve the properties of small molecules. Herein we report the synthesis of a S32826 dendrimer conjugate and its biological evaluation. The conjugate was found to inhibit autotaxin activity using two different substrates and to decrease the migration of an ovarian cancer cell line modified to overexpress autotaxin. Furthermore, the conjugate potentiated activation of caspase 3/7 induced by carboplatin.