Sergy Lemeshko

Metabolically derived potential on the outer membrane of mitochondria: a computational model.

The outer mitochondrial membrane (OMM) is permeable to various small substances because of the presence of a voltage-dependent anion channel (VDAC). The voltage dependence of VDACs permeability is puzzling, because the existence of membrane potential on the OMM has never been shown. We propose that steady-state metabolically derived potential (MDP) may be generated on the OMM as the result of the difference in its permeability restriction for various charged metabolites. To demonstrate the possibility of MDP generation, two models were considered: a liposomal model and a simplified cell model with a creatine kinase energy channeling system. Quantitative computational analysis of the simplified cell model shows that a MDP of up to -5 mV, in addition to the Donnan potential, may be generated at high workloads, even if the OMM is highly permeable to small inorganic ions, including potassium. Calculations show that MDP and DeltapH, generated on the OMM, depend on the cytoplasmic pH and energy demand rate. Computational modeling suggests that MDP may be important for cell energy metabolism regulation in multiple ways, including VDACs permeability modulation and the effect of electrodynamic compartmentation. The osmotic pressure difference between the mitochondrial intermembrane space and the cytoplasm, as related to the electrodynamic compartmentation effects, might explain the morphological changes in mitochondria under intense workloads.

ACR Appropriateness Criteria® Stage I Breast Carcinoma

Stage I breast carcinoma is classified when an invasive breast carcinoma is ≤2 cm in diameter (T1), with no regional (axillary) lymph node metastases (N0) and no distant metastases (M0). The most common sites for metastases from breast cancer are the skeleton, lung, liver, and brain. In general, women and health care professionals prefer intensive screening and surveillance after a diagnosis of breast cancer. Screening protocols include conventional imaging such as chest radiography, bone scan, ultrasound of the liver, and MRI of brain. It is uncertain whether PET/CT will serve as a replacement for current imaging technologies. However, there are no survival or quality-of-life differences for women who undergo intensive screening and surveillance after a diagnosis of stage I breast carcinoma compared with those who do not. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.