The effect of a graded exercise protocol on phosphorus-31 magnetic resonance (MR) spectroscopy of calf skeletal muscle in nine healthy (control) subjects and 16 patients with symptomatic peripheral arterial occlusive disease (PAOD) was assessed. Ankle-brachial pressure indexes were obtained in all 16 patients, and 10 patients underwent peripheral arteriography. Temporal profiles of pH and the inorganic phosphorus (Pi) index were calculated from the spectra. A Pi-index recovery rate constant was calculated for each subject. Arteriograms were graded by calculating the runoff resistance in the limb of interest. The pH profiles during exercise did not differ significantly between the PAOD patients and control subjects. The Pi-index recovery rate constant in the PAOD patients was significantly (P less than .01) smaller than in the control subjects. There was no significant correlation between recovery rate and the ankle-brachial pressure indexes, but there was a strong negative correlation between recovery rates and angiographic resistance grades, with smaller recovery rate constants in patients with increased arterial resistance. It is concluded that P-31 MR spectroscopy shows promise as a direct measure of tissue perfusion. 相似文献
The adenylate cyclase in rat caudate nucleus homogenate could be stimulated by dopamine and less potently by the dopamine D1 receptor specific agonist SKF38393. Agonists selective for mu[D-Ala2, MePhe4Gly(ol)5]enkephalin (DAGO) and delta opioid receptors [D-Pen2, D-Pen5]enkephalin (dPen-dPen), inhibited the dopamine but not the dopamine D1 stimulated adenylate cyclase. The kappa opioid agonist, U69593, had no effect, probably due to low kappa receptor contents in rat caudate nucleus. 10(-4) M of the sigma receptor specific agonist, 1,3-di-o-tolylguanidine (DTG), potentiated the dopamine as well as the dopamine D1 stimulated adenylate cyclase while lower concentrations of DTG had no effect. 相似文献
Introduction: Category fluency is associated with speed-, executive- and semantic impairments in schizphrenia. It has traditionally been linked to negative symptoms, whereas the relation to positive symptoms is mixed. Associations to the consensus negative, positive and disorganisation factors have not been analysed before.
Methods: Animal fluency was administered to 81 patients with schizophrenia. Measures of overall performance and applied strategies were analysed in relation to the Wallwork five-factor PANSS-model.
Results: Negative and disorganisation symptoms were negatively related to overall fluency performance. Positive symptoms were positively related to overall performance when controlling for disorganisation symptoms. Negative symptoms were related to fewer switches, less repetitions, less single animals intrusions, and both less rare and common animals. Positive symptoms were related to more effective retrieval of sub-category exemplars following a sub-category title, whereas there were no relation between symptoms and exemplars when the title was not retrieved. The Beta values of negative and positive symptoms were opposite.
Conclusion: This is the first study showing that positive symptoms are related to increased fluency performance when disorganisation is controlled for. Like previous studies, negative symptoms were found to depress fluency. Strategy measures indicated that negative symptoms predispose for rigidity, whereas positive symptoms facilitate more efficient associative pathways. 相似文献
α- and β-amyrin are pentacyclic triterpenes found in plants and are known to exhibit pronounced anti-inflammatory effects. Here, we evaluated the effects of a 1:1 mixture of α- and β-amyrin (α,β-amyrin) on an experimental model of colitis in mice.
Experimental approach:
Colitis was induced in Swiss male mice by trinitrobenzene sulphonic acid (TNBS) and followed up to 72 h; animals were treated systemically with α,β-amyrin, dexamethasone or vehicle. Macro- and microscopic damage, myeloperoxidase activity and cytokine levels were assessed in colons. Histological sections were immunostained for cyclooxygenase-2 (COX-2), vascular endothelial growth factor, phospho-p65 nuclear factor-κB (NF-κB) and phospho-cyclic AMP response element-binding protein (CREB)
Key results:
TNBS-induced colitis was associated with tissue damage, neutrophil infiltration and time-dependent increase of inflammatory mediators. Treatment with α,β-amyrin (3 mg·kg−1, i.p.) or dexamethasone (1 mg·kg−1, s.c.) consistently improved tissue damage scores and abolished polymorphonuclear cell infiltration. α,β-Amyrin, like dexamethasone, significantly diminished interleukin (IL)-1β levels and partially restored IL-10 levels in colon tissues 72 h after colitis induction, but only α,β-amyrin reduced vascular endothelial growth factor expression by immunohistochemistry. The colonic expression of COX-2 at 24 h and that of phospho-NF-κB and phospho-CREB (peaking at 6 h) after colitis induction were consistently inhibited by both α,β-amyrin and dexamethasone.
Conclusions and implications:
Systemic administration of α,β-amyrin exerted a marked and rapid inhibition of TNBS-induced colitis, related to the local suppression of inflammatory cytokines and COX-2 levels, possibly via inhibition of NF-κB and CREB-signalling pathways. Taken together, our data suggest a potential use of α,β-amyrin to control inflammatory responses in bowel disease. 相似文献
RAS genes are mutated in approximately 30% of all human cancers. Interestingly, there exists a strong bias in favor of mutation of only one of the three major RAS genes in tumors of different cellular origins. NRAS mutations occur in approximately 20% of human melanomas, whereas HRAS and KRAS mutations are rare in this disease. To define the mechanism(s) responsible for this preference in melanocytes, we compared the transformation efficiencies of mutant NRAS and KRAS in immortal, non-transformed Ink4a/Arf-deficient melanocytes. NRAS mutation leads to increased cellular proliferation and is potently tumorigenic. In contrast, KRAS mutation does not enhance melanocyte proliferation and is only weakly tumorigenic on its own. Although both NRAS and KRAS activate mitogen-activated protein kinase signaling, only NRAS enhances MYC activity in these cells. Our data suggest that the activity of specific RAS isoforms is context-dependent and provide a possible explanation for the prevalence of NRAS mutations in melanoma. In addition, understanding this mechanism will have important implications for cancer therapies targeting RAS pathways. 相似文献