A hybrid mathematical modeling approach of the metabolic fate of a fluorescent sphingolipid analogue to predict cancer chemosensitivity.

Sphingolipid (SL) metabolism is a complex biological system that produces and transforms ceramides and other molecules able to modulate other cellular processes, including survival or death pathways key to cell fate decisions. This signaling pathway integrates several types of stress signals, including chemotherapy, into changes in the activity of its metabolic enzymes, altering thereby the cellular composition of bioactive SLs. Therefore, the SL pathway is a promising sensor of chemosensitivity in cancer and a target hub to overcome resistance. However, there is still a gap in our understanding of how chemotherapeutic drugs can disturb the SL pathway in order to control cellular fate. We propose to bridge this gap by a systems biology approach to integrate i) a dynamic model of SL analogue (BODIPY-FL fluorescent-sphingomyelin analogue, SM-BOD) metabolism, ii) a Gaussian mixture model (GMM) of the fluorescence features to identify how the SL pathway senses the effect of chemotherapy and iii) a fuzzy logic model (FLM) to associate SL composition with cell viability by semi-quantitative rules. Altogether, this hybrid model approach was able to predict the cell viability of double experimental perturbations with chemotherapy, indicating that the SL pathway is a promising sensor to design strategies to overcome drug resistance in cancer.

Development of a thiourea derivative polymer combined to a Direct Mercury Analyser for screening and pre-concentration of mercury species.

A new selective polymer has been developed (Patent: P201500704) with high mercury sorption capacity. The combination of this material with a Direct Mercury Analyser (DMA80) has overcome important limitations of this equipment for mercury determination of complex matrix samples, like high saline content, due to the ability of this material to selective and efficient mercury retention. Furthermore, application for fast screening of mercury species in food samples, like fish, is also presented. The polymer material has been synthesized by the precipitation technique, using Azobisisobutyronitrile (AIBN) as initiator, 2-(Methacryloylamino) ethyl 2-Methyl Acrylate (NOBE) as cross-linker, and 1-phenyl-3-(-3-vinyl phenyl) thiourea as monomer. It has been characterized by SEM, TGA, FTIR, and binding isotherms have been established through Langmuir and Freundlich models. Selectivity has been proven by carrying out cross-reactivity experiments.

Anxiolytic and antidepressant-like effects of the hydroalcoholic extract from Aloysia polystachya in rats.

Behavioral effects of a hydroalcoholic extract from leaves of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) were studied in female Sprague-Dawley rats. The extract was administered intraperitoneally and its effects on spontaneous motor activity (total motility, locomotion, rearing and grooming behavior) were monitored. Anxiolytic-like properties were studied in the elevated plus-maze (EPM) test and the possible antidepressant-like actions were evaluated in the forced swimming test (FST). The results revealed that high doses of the extract (25 and 50 mg/kg, i.p.) caused a significant decrease in total motility, locomotion, rearing and grooming behavior. All doses injected (from 1.56 to 50 mg/kg) increased the exploration of the EPM open arms in a similar way to that of diazepam (1 mg/kg, i.p.). In the FST, the extract (12.5, 25 and 50 mg/kg) was as effective as fluoxetine (10 mg/kg, i.p.) and imipramine (12.5 mg/kg, i.p.) in reducing immobility, along with a significant increase in swimming and climbing, respectively. These results suggest that some of the components of the hydroalcoholic extract of A. polystachya, such as thujone and carvone among others, may have sedative, anxiolytic and antidepressant-like properties which deserve further investigation.

Effect of Bothrops asper (Fer-De-Lance) snake venom on erythrocyte membrane. A comparative study.

1. The effect of Bothrops asper venom on erythrocytes of different species, sheep erythrocyte ghost vesicles and liposomes made of phospholipids from sheep erythrocytes was studied. 2. B. asper venom had a direct hemolytic effect on mouse erythrocytes, but no lytic activity on goat, rabbit, horse, toad and sheep erythrocytes. Human erythrocytes were lysed only in the presence of bovine serum albumin and Ca2+. 3. Although the phospholipase A2 activity in the venom might be involved in the lytic effect on mouse erythrocytes, there is also evidence of direct lytic factor(s) acting in the absence of calcium ions. 4. Sheep erythrocytes were modified in order to study the basis of their resistance. Enhancement of membrane fluidity and variation of pH were of no consequence for the resistance of sheep erythrocytes to the action of venom. 5. The reorganization of membranes that takes place during ghost or liposome preparation made them susceptible to B. asper venom-induced disruption. Thus the resistance of sheep erythrocytes seems related to the accessibility of the target.

Uncompensated and discounted Medicaid care provided by physician group practices in Wisconsin.

A survey of a sample of physician group practices in Wisconsin was undertaken to determine the amounts of charity care, bad debt, and discounted Medicaid care that were provided in 1988. Overall, the physician group practices in the sample reported dollar amounts of uncompensated care and discounted Medicaid care that averaged approximately 7.6% of their total billings for the year (1.6% of charity care, 3.0% of bad debt, and 3.0% of discounted Medicaid care). From the dollar totals reported, it was calculated that the individual physicians represented by this sample of group practices were responsible for, on average, +4300 of charity care, +9100 of bad debt, and +7500 of Medicaid discounted services, for a yearly per-physician total of +20,900 of uncompensated care and discounted care provided to uninsured and indigent patients. The results indicate that a majority of the group practices provided more charity care in 1988 than they had 5 years earlier and suggest that the burden of providing uncompensated care tends to fall disproportionately on those group practices that are also providing relatively high levels of service to Medicaid recipients.

The changing managerial role of physician executives.

A survey of tasks performed by a sample of 517 physician executives from the AMA Masterfile was carried out to determine the role played by this group of administrators in health care organizations. In contrast to the findings of previous studies, physician executives appear to have responsibilities in general management as well as clinical management and do not focus primarily on physician and medical staff issues. No significant differences were found among respondents from hospitals, government, academic organizations, group practices/HMOs, and physician executives who spend more than 90 percent of their time in administration. Tasks identified as important for the future but not currently being done were primarily in the category of external activities such as "changing regulations and legislation" and "communicating goals to the public." These results identify an important boundary-spanning role for physician executives in balancing managerial and professional issues of cost, quality, and access in health care organizations. The implications of these findings for the educational needs of physician executives are discussed.