Severe hypernatremia is defined as serum sodium levels above 152 mEq/L, with a mortality rate ≥60%. 85-year-old gentleman was brought to the emergency room with altered level of consciousness after refusing to eat for a week at a skilled nursing facility. On admission patient was nonverbal with stable vital signs and was responsive only to painful stimuli. Laboratory evaluation was significant for serum sodium of 188 mmol/L and water deficit of 12.0 L. Patient was admitted to medicine intensive care unit and after inadequate response to suboptimal fluid repletion, hemodialysis was used to correct hypernatremia. Within the first fourteen hours, sodium concentration only changed 1 mEq/L with a fluid repletion; however, the concentration dropped greater than 20 mEq/L within two hours during hemodialysis. Despite such a drastic drop in sodium concentration, patient did not develop any neurological sequela and was at baseline mental status at the time of discharge.

Pancreatic cancer remains one of the cancers for which survival has not improved substantially in the last few decades. Only 7% of diagnosed patients will survive longer than five years. In order to understand and mimic the microenvironment of pancreatic tumors, we utilized a murine orthotopic model of pancreatic cancer that allows non-invasive imaging of tumor progression in real time. Pancreatic cancer cells expressing green fluorescent protein (PANC-1 GFP) were suspended in basement membrane matrix, high concentration, (e.g., Matrigel HC) with serum-free media and then injected into the tail of the pancreas via laparotomy. The cell suspension in the high concentration basement membrane matrix becomes a gel-like substance once it reaches room temperature; therefore, it gels when it comes in contact with the pancreas, creating a seal at the injection site and preventing any cell leakage. Tumor growth and metastasis to other organs are monitored in live animals by using fluorescence. It is critical to use the appropriate filters for excitation and emission of GFP. The steps for the orthotopic implantation are detailed in this article so researchers can easily replicate the procedure in nude mice. The main steps of this protocol are preparation of the cell suspension, surgical implantation, and whole body fluorescent in vivo imaging. This orthotopic model is designed to investigate the efficacy of novel therapeutics on primary and metastatic tumors.

Pancreatic cancer remains one of the cancers for which survival has not improved substantially in the last few decades. Only 7% of diagnosed patients will survive longer than five years. In order to understand and mimic the microenvironment of pancreatic tumors, we utilized a murine orthotopic model of pancreatic cancer that allows non-invasive imaging of tumor progression in real time. Pancreatic cancer cells expressing green fluorescent protein (PANC-1 GFP) were suspended in basement membrane matrix, high concentration, (e.g., Matrigel HC) with serumfree media and then injected into the tail of the pancreas via laparotomy. The cell suspension in the high concentration basement membrane matrix becomes a gel-like substance once it reaches room temperature; therefore, it gels when it comes in contact with the pancreas, creating a seal at the injection site and preventing any cell leakage. Tumor growth and metastasis to other organs are monitored in live animals by using fluorescence. It is critical to use the appropriate filters for excitation and emission of GFP. The steps for the orthotopic implantation are detailed in this article so researchers can easily replicate the procedure in nude mice. The main steps of this protocol are preparation of the cell suspension, surgical implantation, and whole body fluorescent in vivo imaging. This orthotopic model is designed to investigate the efficacy of novel therapeutics on primary and metastatic tumors.

Prior EPR oximetry work by Subczynski and colleagues has shown that cholesterol increases membrane resistance to oxygen permeation by 3-to 5-fold when present in a 1:1 ratio with phospholipid. In the current study, we use molecular dynamics simulations to investigate the biophysics of oxygen transport in membranes incorporating cholesterol. The simulations enable cross-validation of the EPR oximetry measurements and the simulations. Further, we have been able to observe oxygen transport near the bilayer surface, which has not been accessible to EPR spin-label probes. We find excellent agreement between the simulation and EPR observations. Our simulations affirm that cholesterol reduces oxygen flux when present at a 1:1 ratio with phospholipid. They further indicate that the bilayer surface in the presence or absence of cholesterol presents greater resistance to permeation than previously observed by EPR.

No abstract