The role of growth factors and cytokines in the impaired healing of chronic leg ulcers remains uncertain. The aim of this study was to determine whether changes in the amount and location of cytokines and growth factors may be associated with impaired healing in chronic leg ulcers. Biopsies from leg ulcers of 21 patients and from normal skin of nine healthy volunteers were examined immunohistochemically for selected growth factors and cytokines. Greater staining intensity was found in keratinocytes at the edges of ulcers compared to normal skin, or skin adjacent to the ulcers. Staining at the ulcer edge was more intense in nonhealing ulcers for only vascular endothelial growth factor and platelet-derived growth factor, whereas staining in the adjacent skin was more intense for all factors in the nonhealing phase. For all factors staining was cytoplasmic, suggesting production in these areas. This study shows up-regulation of the production of cytokines and growth factors in keratinocytes of chronic leg ulcers that is greater when the ulcers are nonhealing. 相似文献
Background: The objective of this study was to identify the extent to which propofol alters intracellular free Ca2+ concentration ([Ca2+]i), myofilament Ca2+ sensitivity, and contraction of individual cardiomyocytes during activation of [alpha]1a adrenoreceptors and to determine the cellular mechanism of action.
Methods: Freshly isolated ventricular myocytes were obtained from adult rat hearts. Myocyte shortening and [Ca2+]i were simultaneously monitored in individual cardiomyocytes exposed to phenylephrine after treatment with chloroethylclonidine ([alpha]1b-adrenoreceptor antagonist) and BMY 7378 ([alpha]1d-adrenoreceptor antagonist). Data are reported as mean +/- SD.
Results: Phenylephrine increased myocyte shortening by 124 +/- 9% (P = 0.002), whereas peak [Ca2+]i only increased by 8 +/- 3% (P = 0.110). Inhibition of phospholipase A2 and phospholipase C attenuated the phenylephrine-induced increase in shortening by 84 +/- 11% (P = 0.004) and 15 +/- 6% (P = 0.010), respectively. Inhibition of protein kinase C (PKC) and Rho kinase attenuated the phenylephrine-induced increase in shortening by 17 +/- 8% (P = 0.010) and 74 +/- 13% (P = 0.006), respectively. In the presence of phenylephrine, propofol increased shortening by 40 +/- 6% (P = 0.002), with no concomitant increase in [Ca2+]i. PKC inhibition prevented the propofol-induced increase in shortening. Selective inhibition of PKC[alpha], PKC[delta], PKC[varepsilon], and PKC[zeta] reduced the propofol-induced increase in shortening by 12 +/- 5% (P = 0.011), 36 +/- 8% (P = 0.001), 32 +/- 9% (P = 0.007), and 19 +/- 5% (P = 0.008), respectively. Na+-H+ exchange inhibition reduced the propofol-induced increase in shortening by 56 +/- 7% (P = 0.001). 相似文献
BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147- 325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61- 140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64- 206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease. 相似文献
Follistatin is a binding protein for the activin and inhibin family of
hormones, regulating their biological activity. In the male reproductive
tract, the interaction of these factors is likely to be involved in the
regulation of the proliferation of several cell types. We have investigated
the presence of follistatin and activin A in seminal plasma using specific
immunoassays and have localized follistatin and activin/inhibin subunits in
the adult human testis, prostate and seminal vesicle to establish their
likely sources. High concentrations of immunoreactive follistatin were
present in seminal plasma in normal men (mean 97.9 ng/ml; 1.43 ng/ml in
peripheral plasma) and were similar in men with oligo/azoospermia and
following vasectomy. Follistatin immunoreactivity was localized to both
Leydig and Sertoli cells of the testis, and to epithelial cells of the
prostate gland and seminal vesicle, which are likely to be the predominant
sources of the hormone in seminal plasma. Activin A was also present in
seminal plasma in normal men but was undetectable following vasectomy, thus
deriving from the testis. Consistent with this finding, the betaA-subunit
was immunolocalized in Sertoli and Leydig cells but was not present in
seminal vesicle or prostate gland. The functional significance of the high
concentrations of follistatin secreted into seminal plasma by the prostate
gland and/or seminal vesicle is uncertain, but they may regulate the
biological activity of testis-derived activin A and inhibin B.
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Retrospective review of 363 consecutive autopsy reports in which adrenal examination was noted reveal 8 cases of pigmented adrenal nodules. Black pigmented adrenal nodules have been reported infrequently both as incidental autopsy findings and in association with Cushing's syndrome. The nature of the pigment in these lesions has been assumed to be lipofuscin. Gross and histologic study of seven cases and electron microscopic study of two cases suggest the presence of a neuromelanin component in the pigment, a previously unreported finding in the adrenal cortex. Review of the clinical records of the patients suggested no associations with specific underlying disorders. The prevalence the authors report (2.2%) is less than that of a previous prospective study. 相似文献