Extraneous factors affecting resistive index

Recently, numerous studies have referred to the resistive index as an accurate indicator of acute renal transplant rejection. We encountered several factors other than rejection that resulted in an elevation of the resistive index in both clinical and experimental situations. Any compressive effect on the kidney will elevate the resistive index. This compression may arise from an adjacent mass such as a fluid collection, most commonly hematoma, or even from excessive pressure transmitted via the transducer by a heavy-handed technician. Resistive index elevation also has been demonstrated in experimentally induced hypotension. Technically inaccurate scanning can yield a falsely low resistive index, but these previously mentioned entities can falsely elevate it, leading to an incorrect diagnosis of acute rejection.     

Heart rate reduces when stroke patients are touched . . . And??

McFadden KL, Hernández TD. Cardiovascular benefits of acupressure (Jin Shin) following stroke. Complement Ther Med 2010; 18: 42–8.     

Inactivation of primary antioxidant enzymes in mouse keratinocytes by photodynamically generated singlet oxygen

Cellular antioxidant enzymes protect against damage caused by exposure to endogenous or exogenous prooxidants. Singlet oxygen ((1)O(2)) is a reactive form of oxygen that can be produced in vivo either in normal and pathophysiologic conditions or by photosensitizing chemicals, as during photodynamic treatment. We hypothesized that photodynamically generated (1)O(2) would decrease the enzymatic activities of cellular antioxidants. To test this hypothesis, we treated cultured mouse epidermal keratinocytes with the photosensitizer Photofrin plus visible light to produce (1)O(2), and then measured CuZnSOD, MnSOD, and catalase activities with both ingel and spectrophotometric enzyme activity assays. Our results demonstrated that the enzymatic activities of cellular CuZnSOD, MnSOD, and catalase were significantly decreased after keratinocytes were treated with Photofrin plus visible light. By contrast, the enzymatic activities of cellular CuZnSOD, MnSOD, and catalase were unaffected in control cells treated with Photofrin only or visible light only. Despite the decreased levels of enzymatic activities, the protein levels of all three primary antioxidant enzymes remained constant after photodynamic treatment, as determined by Western blotting. L-Histidine, a (1)O(2) quencher, protected against the inactivation of cellular CuZnSOD, MnSOD, and catalase enzymes induced by photodynamically generated (1)O(2). The conclusion from these experiments is that the primary cellular antioxidant enzymes CuZnSOD, MnSOD, and catalase can be inactivated by photodynamically generated (1)O(2) in nucleated mammalian cells. These findings may be useful in the future development of antineoplastic adjuvant therapies that use photodynamic generation of (1)O(2) to inactivate antioxidant defenses with a goal of sensitizing tumor cells to prooxidant-generating drugs.     

Differential effect of phorbol esters and interleukin-3 on protein kinase C isoform content and kinase activity in the FDC-P1 cell line

FD/PMA is a subclone of the interleukin-3 (IL-3)-dependent, FDC-P1 cell line, which proliferates in response to either 12-O- tetradecanoylphorbol-13 acetate (PMA) or IL-3. While several endogenous substrates were phosphorylated in response to protein kinase C (PKC) activation in FDC-P1, phospholipid-dependent phosphorylation in the FD/PMA grown in PMA was not observed. Basal, phosphatidylserine- independent, and diolein-independent phosphorylation of cytosolic substrates with molecular weights of 17, 52, 57, and 105 Kd were enhanced in FD/PMA cells grown in PMA as compared with FDC-P1 cells cultured in IL-3. Phosphorylation of a 105-Kd substrate was enhanced in the particulate fraction of FD/PMA cells maintained in PMA. The 17-Kd substrate in FD/PMA cells comigrated with a substrate phosphorylated in a PKC-dependent manner in FDC-P1 cells. Phosphorylation of the 52- and 57-Kd substrates, but not of the 17-Kd substrate, was inhibited by H-7 and staurosporine. A portion of the PMA-induced cytosolic kinase activity coeluted with PKC on diethyl aminoethyl chromatography. While FD/PMA cells cultured in PMA contained negligible PKC-dependent phosphorylation of endogenous substrates or histone, alpha and epsilon PKC isoforms were detected by Western blot analysis. PKC phosphotransferase activity was observed in FD/PMA cells grown in PMA when peptides corresponding to residues 720 to 737 of PKC-epsilon or residues 4 to 14 of myelin basic protein were used as substrates. These data indicate that maintenance of FD/PMA cells in PMA stimulates proliferation and markedly alters PKC substrate specificity. Generation of at least two phospholipid-independent kinases occurs in PMA-treated cells.     

Disruption of cellular energy balance by suramin in intact human prostatic carcinoma cells, a likely antiproliferative mechanism.

The antiparasitic drug, suramin, has antiproliferative effects in human carcinoma cells. It has been suggested that this occurs through blockade of growth factor-receptor interactions. Three types of evidence that suramin rapidly inhibits cellular respiration or disrupts cellular energy balance in intact cells of the human prostate carcinoma cell line, DU145, are presented. Beginning at approximately 10(-4) M, suramin rapidly causes dose-dependent inhibition of tetrazolium conversion by mitochondrial dehydrogenases in intact cells, demonstrating an inhibition of respiration. This effect is reversed by exchange with suramin-free media but not by pretreatment with serum, epidermal growth factor, insulin-like growth factor I, acidic and basic fibroblast growth factors, or calcium. Rhodamine 123 (10 micrograms/ml) uptake by mitochondria in intact DU145 cells is inhibited in the presence of 10(-3) M suramin. Treatment with 10(-4)-10(-3) M suramin causes the loss of rhodamine 123 from cells with mitochondria prestained with rhodamine 123, indicating that suramin is acting as an ionophore or respiratory poison. Also shown by electron microscopy are progressive toxic changes in mitochondria of DU145 cells within 1 h after treatment with 10(-4) M suramin. These data indicate that in intact DU145 cells 10(-4) M suramin rapidly disrupts cellular energy balance or respiration as seen by three studies of mitochondrial state. Disruption of energy balance or respiration represents a likely antiproliferative mechanism, as is thought to be a primary mechanism for the action of suramin in parasitic diseases. This proposed mechanism of action for suramin can explain the most prominent observed clinical toxicities of nephrotoxicity, adrenal toxicity, coagulopathy, and demyelinating neuropathy.     

Cell differentiation, aging and cancer: the possible roles of superoxide and superoxide dismutases

A unified theory of cell differentiation, aging, and cancer is discussed. All cells are hypothesized to originate from stem cells. These stem cells mature as they divide and eventually reach a fully differentiated cell, which cannot divide. Aging is caused by the loss of stem cells, either due to cell death or terminal differentiation, and by eventual death of fully differentiated cells. Both loss of stem cells and death are brought about by oxygen radicals. The cancer phenotype is caused by an inability of a stem cell to differentiate fully under the local environmental conditions. Because the cancer cell cannot differentiate, it never loses its potential for growth. The block in differentiation of cancer cells is caused by a relative lack of radical scavengers, particularly manganese superoxide dismutase, coupled with production of radicals, especially superoxide. The high reactivity of these radicals leads to changes in key subcellular structures and prevents the cell from attaining the organization needed for cell differentiation to occur.