The TPA score (total psoas muscle area) is the best marker for preoperative measurement of pre-sarcopenia in pancreatic surgery.

INTRODUCTION: Pre-sarcopenia, defined by the loss of muscle mass, is significantly associated with an increased risk of postoperative complications in digestive surgery, particularly pancreatic resection. The five predominant markers of sarcopenia are: psoas muscle area (TPA), intramuscular adipose tissue content (IMAC), Average Hounsfield Unit Calculation (HUAC), Skeletal Muscle Mass Index (MMI), and the ratio between visceral adipose tissue area and muscle surface area (VFA/TAMA). No standard reference marker has been determined. MATERIAL AND METHODS: This retrospective cohort included patients who underwent pancreatic resection at the University Hospital of Angers between January 2008 and June 2017. The goal was to determine the marker that was most significantly associated with morbidity and mortality in pancreatic surgery. The secondary objective was to determine the characteristics of pre-sarcopenic patients. RESULTS: The TPA score is the most sensitive marker for identifying patients at highest risk for immediate complications (P=0.008), proving far more sensitive than MMI (P=0.02), HUAC (P=0.34), IMAC (P=1), or VFA/TAMA (P=0.42). Postoperative mortality was 3.3% (n=5), morbidity was 63.8% (n=97). Pre-sarcopenic patients, as identified by the TPA index had significantly more immediate complications (71.2% versus 49.5%, P=0.008), in particular, more gastroparesis (P=0.02) and pancreatic fistula (P=0.03). CONCLUSION: In patients requiring pancreatic surgery, the prevalence of pre-sarcopenia is high and seems to be associated with a greater risk of immediate postoperative complications. The TPA score seems to be the most sensitive marker for detecting pre-sarcopenia. Evaluation of TPA preoperatively would make it possible to identify priority patients a priori who might benefit from pre-habilitation programs.

Proliferation and Na+/H+ exchange activation by endothelin in vascular smooth muscle cells.

Initiation and development of proliferative responses to growth factors are often associated to an activation of the Na+/H+ exchange. The present work examined the effect of endothelin (ET-1) on cell proliferation and Na+/H+ exchange in cultured vascular smooth muscle cells. In rat aortic vascular smooth muscle, ET-1 (0.1 to 10 nmol/L) increased the [3H] thymidine uptake in a dose-dependent manner. This effect was enhanced in presence of insulin (0.1 micrograms/mL to 10 micrograms/mL) as a function of concentration. The Na+/H+ exchange, which is a necessary response for mitogenesis, was dose-dependently stimulated by increasing concentrations of ET-1 (1 to 1000 nmol/L) and presented a biphasic response: a transient acidification followed by a sustained alkalinization. Alkalinization induced by ET-1 was similar to that obtained by the phorbol 12-myristate 13-acetate (PMA). An inhibitor of protein kinase C, H7, or a long-term pretreatment of cells with PMA for 24 h inhibited the effect of ET-1 and PMA on Na+/H+ exchange. These results confirm that ET-1 could act as a growth factor for vascular smooth muscle cells and suggest that its mode of action depends for a large part to protein kinase C activation.

[Effect of endothelin on the proliferation of aortic smooth muscle cells in normotensive and spontaneously hypertensive rats]. / Effet de l'endothéline sur la prolifération de cellules musculaires lisses d'aorte de rats normotendus et spontanément hypertendus.

In order to examine the effect of endothelin (ET-1) as a growth factor, vascular smooth muscle cells were isolated from aortas of spontaneously hypertensive (SHR) and control (WKY) rats. Cell proliferation was determined by measurement of labelled 3H-thymidine incorporation in quiescent cells in presence of ET-1 alone or in association with another growth factor, insulin (INS). ET-1 alone (0.1 to 100 nM) increased slightly the growth of both types of cells. This effect was enhanced in presence of INS (0.1 to 10 micrograms/ml). SHR cells were more reactive than control ones. Activation of Na+/H+ exchange which is a necessary response for mitogenesis was dose dependently observed with increasing concentrations of ET-1 (0.1 to 100 nM) further confirming that ET-1 could act as a growth factor for vascular smooth muscle cells.

[Stimulation of calcium flows induced by endothelin in cultured smooth muscle cells]. / Stimulation des flux calciques induits par l'endothéline dans des cellules muscularies lisses en culture.

Endothelin is a potent vasoconstrictor peptide isolated from the conditioned medium of porcine aortic endothelial cells. The action of endothelin is thought to be associated with calcium entry via calcium potential channels (Yanagisawa et. al. Nature 1988; 38:411-415). The present study was designed to determine the effect of endothelin on calcium fluxes (influx and efflux) on rat aortic smooth muscle cells in culture. The unidirectional influx of calcium was measured 15, 45, 75 and 105 seconds after the addition of trace amounts of 45Ca++ (5 microCi/ml) to the cells incubated with or without endothelin. Endothelin (50nM) stimulated calcium influx from a basal level of 312 +/- 17 to 537 +/- 12 pmol/mn/10(6) cells. This stimulation was dose-dependent with an EC50 value of about 10 nM. When cells were preincubated with calcium antagonists (nifedipine, dilttiazem, D600, nicardipine and flunarizine) at a final concentration of 1 microM, the endothelin-stimulated calcium influx was not modified. The unidirectional efflux of calcium was measured after an overload of cells with 45Ca++ (5 microCi/ml) for 18 hours, over 10 seconds intervals. In the first 30 seconds after the addition of endothelin (100 nM), the amount of 45Ca++ released was 3 times that in the absence of the peptide. The effect of endothelin was concentration dependent and similar to those observed with other vasoconstrictor peptides (vasopressin and angiotensin II). The results indicate that endothelin does not directly act on voltage-dependent calcium channels. The endothelin-stimulated calcium efflux suggests a mobilization of calcium from intracellular store sites followed by extrusion through an activation of a specific receptor-dependent calcium channel.

Restriction endonuclease analysis of human cytomegalovirus isolated in immunocompromised patients.

Cytomegalovirus is frequently isolated from immunosuppressed patients or from patients with acquired immunodeficiency syndrome. Twelve patients were studied for several months. In 7 patients more than 1 Cytomegalovirus was isolated; in one of these patients three viruses were isolated, two of them show small differences in their migration pattern and the third seems to be a different strain after restriction analysis of CMV genome. This could reflect variation in the genome of the CMV virus as it has been already shown for viruses from other families in immunocompromised patients and shows the occurrence of multiple strains infection in a single patient.

Inhibition of histamine-induced Ca2+ efflux in cultured vascular smooth muscle cells by an antihypertensive drug, cicletanine.

The effect of cicletanine, a new antihypertensive drug, on histamine-induced Ca2+ release in cultured vascular smooth muscle cells from guinea-pig aorta was examined. In 45Ca2+ labelled cells, histamine increased in a dose-dependent manner the Ca2+ efflux (EC50 = 8 x 10(-6) M). This stimulation of 45Ca2+ efflux was also observed with an H1-agonist [2-pyridylethylamine dihydrochloride (2-PEA)] but not with an H2-agonist (dimaprit). Histamine- or 2-PEA-induced 45Ca2+ efflux was inhibited by an H1-antagonist (mepyramine), whereas an H2-antagonist (cimetidine) had no effect. Cicletanine was as effective as the H1-antagonist in inhibiting histamine- or 2-PEA-stimulated 45Ca2+ efflux in a dose-dependent manner (IC50 = 10(-6) M). Only the racemic form and the R(-) enantiomer of cicletanine behaved as histaminergic antagonists, the S(+) enantiomer having no effect. These results suggest that the direct effect of cicletanine on the mobilization of Ca2+ by blocking H1-receptors may participate in an antihypertensive mechanism by producing relaxation of blood vessels.

Down-regulation of atrial natriuretic factor receptors and correlation with cGMP stimulation in rat cultured vascular smooth muscle cells.

The relationship between the binding of 125I-labeled rat ANF and the responsiveness in cGMP production of ANF receptors were examined in cultured rat thoracic smooth muscle cells after preexposure with the peptide. Binding assay of 125I-labeled ANF showed a specific, reversible and saturable binding with a KD value of 3.1 +/- 0.3 10(-10) M and a maximum binding (Bmax) of 240 +/- 30 fmol/10(6) cells. Pretreatment of the cells with increasing concentrations of unlabeled ANF (10(-9) M to 10(-7) M) resulted in a dose-dependent decrease of the number of binding sites without a change in the affinity. This effect was clearly associated with a desensitization of ANF-induced cGMP production.