ABSTRACT
Ghrelin has been shown to accelerate gastric emptying in animals where its effect appeared mediated through the vagus nerve. We aimed to verify the gastrokinetic capacity of ghrelin in human. Patients with gastroparesis attributed to a neural dysregulation by diabetes (n = 5) or surgical vagotomy (n = 1) were evaluated. The emptying of a test meal (420 kcal) was determined by the C13 octanoic acid breath test. Saline or synthetic ghrelin 1-4 microg/kg were given in 1 min bolus at the end of the meal. T-lag and T-1/2 were shorter during ghrelin than during saline administration [33 +/- 5 min versus 65 +/- 14 min (p < 0.01) and 119 +/- 6 min versus 173 +/- 38 min (p < 0.001)]. Ghrelin injection therefore accelerated gastric emptying of a meal in humans even in presence of a deficient gastric innervation.
Subject(s)
Gastroparesis/drug therapy , Gastroparesis/metabolism , Peptide Hormones/administration & dosage , Peptide Hormones/physiology , Adult , Female , Gastric Emptying/drug effects , Gastric Mucosa/metabolism , Ghrelin , Humans , Middle Aged , Peptide Hormones/metabolism , Peptides/chemistry , Time FactorsABSTRACT
The expression and function in growth and apoptosis of the renin-angiotensin system (RAS) was evaluated in human glioblastoma. Renin and angiotensinogen (AGT) mRNAs and proteins were found by in situ hybridisation and immunohistochemistry in glioblastoma cells. Angiotensinogen was present in glioblastoma cystic fluids. Thus, human glioblastoma cells produce renin and AGT and secrete AGT. Human glioblastoma and glioblastoma cells expressed renin, AGT, renin receptor, AT(2) and/or AT(1) mRNAs and proteins determined by RT-PCR and/or Western blotting, respectively. The function of the RAS in glioblastoma was studied using human glioblastoma cells in culture. Angiotensinogen, des(Ang I)AGT, tetradecapaptide renin substrate (AGT1-14), Ang I, Ang II or Ang III, added to glioblastoma cells in culture, did not modulate their proliferation, survival or death. Angiotensin-converting enzyme inhibitors did not diminish glioblastoma cell proliferation. However, the addition of selective synthetic renin inhibitors to glioblastoma cells decreased DNA synthesis and viable tumour cell number, and induced apoptosis. This effect was not counterbalanced by concomitant addition of Ang II. In conclusion, the complete RAS is expressed by human glioblastomas and glioblastoma cells in culture. Inhibition of renin in glioblastoma cells may be a potential approach to control glioblastoma cell proliferation and survival, and glioblastoma progression in combination therapy.
Subject(s)
Angiotensinogen/metabolism , Apoptosis , Brain Neoplasms/metabolism , Glioblastoma/metabolism , Renin/metabolism , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensinogen/genetics , Animals , Brain Neoplasms/pathology , Brain Neoplasms/surgery , CHO Cells , Cell Division/drug effects , Cricetinae , Glioblastoma/pathology , Glioblastoma/surgery , Humans , Immunoenzyme Techniques , In Situ Hybridization , Protease Inhibitors/pharmacology , RNA, Messenger/metabolism , Receptor, Angiotensin, Type 1/genetics , Receptor, Angiotensin, Type 1/metabolism , Receptor, Angiotensin, Type 2/genetics , Receptor, Angiotensin, Type 2/metabolism , Renin/genetics , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , Serine Proteinase Inhibitors/genetics , Serine Proteinase Inhibitors/metabolism , Tumor Cells, CulturedABSTRACT
Stress relaxation of four temporary restoratives was studied. In the vicinity of ambient mouth temperature, the relaxation characteristics of an unmodified zinc oxide-eugenol cement were more favorable than those of IRM and Cavit. The plastic behavior of gutta-percha temporary stopping precluded assessment of its relaxation at temperatures in excess of 22 degrees C.
