A quantitative systems pharmacology model of plasma potassium regulation by the kidney and aldosterone.

Plasma potassium regulation within a narrow range is vital for life. The risk for hyperkalemia increases when kidney function is impaired and with therapeutic interventions such as mineralocorticoid receptor antagonists (MRAs). The kidney maintains potassium homeostasis by matching potassium intake and excretion, in part through the action of aldosterone. A mechanistic mathematical model was developed and used to investigate the effect of renal impairment and MRAs on plasma potassium levels. The model describes renal potassium filtration, reabsorption, and secretion along the nephron; potassium-aldosterone regulatory feedbacks; whole body potassium balance; and the pharmacologic effects of MRAs. The model was calibrated by fitting (1) the plasma potassium and aldosterone response to potassium infusion in humans on high/low potassium diets, and (2) the acute potassium excretion response to spironolactone. The model was validated by predicting steady-state plasma potassium with sustained spironolactone treatment in hyperaldosteronism patients. The model was then used to demonstrate that (1) declining renal function alone has a small effect on plasma potassium for GFR > 30 ml/min, but an increasing effect as GFR approaches end stage renal disease (GFR ~ 15 ml/min) (2) the effect of increasing potassium intake has minimal effect at normal GFRs but increasing effect on plasma potassium as GFR declines, and 3) MRAs have a minor effect on plasma potassium when GFR is normal, but cause larger increases as GFR falls below 60 ml/min. This model provides a quantitative framework for investigating integrated impacts of diseases and therapies in this complex system.

Use of a smartphone thermometer to monitor thermal conductivity changes in diabetic foot ulcers: a pilot study.

OBJECTIVE: To investigate the dependability of a thermal gadget connecting to a smartphone. Comparing the exact temperature of damaged tissue with adjacent parts of the limb and to evaluate the changes in thermal conductivity of hard-to-heal wounds in patients with a diabetic foot ulcer (DFU). METHODS: Potential candidates were divided into three groups and selected from different hospitals in Tehran. Group 1 contained patients with inflammation, Group 2 were patients with vascular complications, and Group 3 were patients who were managing to control their glucose levels to an acceptable level, according to their medical records (i.e. 'healthy cases'). All thermal images were taken without any external stimulus, in room temperature conditions after 15 minutes' rest. All medical records were confirmed by therapeutic supervisors. Moreover, the tissue conditions in patients were considered in the computational part of the study. The temperatures of the ulcer and adjacent tissues were observed and compared. The collected data were used in a suggested model for human tissues and the method of calculation in this study was trial and error. In this study, patients in Group 2 were considered in the computational section of the study. RESULTS: Temperature difference between the wounds and adjacent tissues for the big toe in three patients in Group 2 was 2.2ºC for the healthier candidate and almost 6.9ºC in the worst case. By comparing the thermal conductivity of normal and damaged tissues, a significant reduction in thermal conductivity was observed for the candidate with the worst status of big toe by about 84.3%. For the other two candidates in this category, it was almost 68.86% and 20.47%. CONCLUSION: The variation in thermal conductivity represents the change in tissue properties. Thermal conductivity can be applied for early DFU detection. This data may allow introduction of the smartphone thermometer as an authentic and alternative apparatus that is beneficial in diabetic clinics as well as self-assessment by patients. Moreover, due to the decrease in thermal conductivity, this study suggests using intelligent thermal sheets in vulnerable parts of the diabetic foot.