None.

Mechanisms that function to regulate the rate of de novo phosphatidylinositol (PtdIns) synthesis in mammalian cells have not been elucidated. In this study, we characterize the effect of phorbol ester treatment on de novo PtdIns synthesis in C3A human hepatoma cells. Incubation of cells with 12-O-tetradecanoyl phorbol 13-acetate (TPA) initially (1-6 h) results in a decrease in precursor incorporation into PtdIns; however, at later times (18-24 h), a marked increase is observed. TPA-induced glucose uptake from the medium is not required for observation of the stimulation of PtdIns synthesis, because the effect is apparent in glucose-free medium. Inhibition of the activation of arachidonic acid substantially blocks the synthesis of PtdIns but has no effect on the synthesis of phosphatidylcholine (PtdCho). Increasing the concentration of cellular phosphatidic acid by blocking its conversion to diacylglycerol, on the other hand, enhances the synthesis of PtdIns and inhibits the synthesis of PtdCho. The TPA-induced stimulation of PtdIns synthesis is not the result of the concomitant TPA-induced G1 arrest, because G1 arrest induced by mevastatin has no effect on PtdIns synthesis. Inhibition of protein kinase C activity blocks the stimulatory action of TPA on de novo synthesis of PtdIns but has no effect on TPA-induced inhibition.Potential sites of enzymatic regulation are discussed.-Nuwayhid, S. J., M. Vega, P. D. Walden, and M. E. Monaco. Phosphatidylinositol (PtdIns) is an essential acidic phospholipid found in the membranes of mammalian cells (1) as well as on the chromatin (2). A single molecular species composed of stearate (R9) and arachidonate (R99) accounts for z80% of the total PtdIns. There are two pathways for the synthesis of PtdIns: the de novo pathway and the salvage pathway, which converge at the level of phosphatidic acid (PtdOH). The de novo pathway uses dihydroxyacetone phosphate derived from glucose to make glycerol phosphate, which is subsequently acylated at the sn-1 position with stearate and then at the sn-2 position with arachidonate to yield PtdOH. In the salvage pathway, diacylglycerol (DAG), derived from phospholipase C-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdInsP 2 ), is converted to PtdOH through the action of DAG kinase. In the first instance, there is a net increase in PtdIns, whereas in the second, there is not. The central element of both pathways is the production of PtdOH. For the salvage pathway, it appears that the conversion of DAG to PtdOH by DAG kinase is stimulated as a result of agonist-induced polyphosphoinositide turnover. Whether this results from an increase in DAG substrate and/or an increase in DAG kinase enzyme activity is unclear. This laboratory has previously demonstrated that the two pathways can be differentiated in situ on the basis of the inhibition by triacsin C, a specific inhibitor of arachidonate-specific long-chain fatty acyl-CoA synthetase (ACSL4) in situ (3, 4).Although regulation of the salvage pathway via the activation ...

Timely access to surgical care is crucial to the development of resilient healthcare systems, society and economic growth (Meara et al., 2015). Using a biosocial approach, this study aimed to (1) identify and understand barriers, delays and facilitators affecting rural patients' surgical care access; and (2) investigate the role that Cinterandes mobile surgery plays in surgical care in five rural Ecuadorian communities. This qualitative assessment employed an inductive, content analytic approach to document experiences and opinions on accessing surgical services in rural Ecuador. We sought to understand the perspectives on surgical access from a variety of informants including rural patients, healthcare providers, healthcare workers, healthcare leaders and rural community leaders. We conducted 36 multi-vocal semistructured interviews to include participants from five rural communities within Azuay and Cañar provinces in the Andean highlands, Morona-Santiago province in the Amazon rainforest, and Santa Elena province in the coastal region; and also interviewed members of the Cinterandes Foundation, an Ecuadorian mobile surgery program. iv We found nine barriers and delays in the care seeking process of rural patients. These include unfamiliarity with hospitals, doctors and urban settings; the responsibility of the family unit, distrust in the public healthcare system, health system inefficiencies, displacement of decision-making power, strong regulations on non-governmental organizations, unique remoteness of the Amazon, the negative impact that lack of supplies has on delivery of surgical care, and the conflict between the assumptions and practices about rural patient's use of traditional medicine. In addition, we found three facilitators including (1) the benefit of the family unit; (2) Socialización (an educational process that brings together rural patients and physicians to deepen patients' understandings of surgical illness, surgical care and break biosocial barriers); and (3) the importance of surgeons or physicians visiting patients' homes. In analyzing biosocial issues, we found that structural violence embedded in historical, social, political and healthcare system structures hindered rural patient's ability to access surgical care. We described how Cinterandes mobile surgery addresses the three delays in surgical care and described the Cinterandes mobile surgery model of care. Moreover, we redefined Cinterandes mobile surgery as a Community-Based Surgical Care Accompaniment Model. Based on this analysis we offer recommendations that we hope will inform and guide future decisions to optimize the surgical care delivery system and help decrease barriers to surgical care for rural patients.