Somatostatin inhibits colonic ion secretion in animal models and cultured intestinal cell lines via somatostatin receptor subtype 2 and subtype 1, respectively. In a recent in vitro ion transport ...study of the human colon, somatostatin was shown to stimulate short-circuit current, a measure of electrogenic ion transport. In this study we have used the reverse-transcription polymerase chain reaction (RT-PCR) and measurements of changes in short-circuit current (Isc) in response to receptor subtype-specific analogs of somatostatin, to define the somatostatin receptor subtype responsible for the stimulation of short-circuit current in human colon. Somatostatin receptor subtypes 1, 2, and 5, but not 3 and 4, were detected in the human colonic epithelium. Measurements of short-circuit current showed somatostatin and octreotide (1 micromol/liter) increased the prostaglandin stimulated short-circuit current by 12.3+/-1 and 11.0+/-1 microA/cm2, respectively. Similarly, analogs selective for somatostatin receptor subtypes 2 and 5 (1 micromol/liter) produced an increase of short-circuit current of 11.7+/-1 and 13.2+/-1 microA/cm2, respectively. However, at a concentration (10 nmol/liter) near the EC50, the somatostatin receptor subtype 2 analog increased short-circuit current by 9+/-1 microA/cm2, whereas the receptor subtype 5 analog had no effect. There was no difference in receptor expression or effect of the peptides related to the anatomical site of tissue collection. In conclusion, human colonic mucosa expresses multiple somatostatin receptor subtypes, of which subtype 2 mediates the stimulatory effect of somatostatin on ion transport.
Barrett's oesphagus is characterised by the presence of specialised intestinal metaplasia in the lower oesphagus. Its importance is related primarily to its link with adenocarcinoma of the lower ...oesphagus, often preceded by dysplastic changes. The incidence of this carcinoma has increased dramatically over the last few decades Although modern treatments, particularly acid suppression with proton pump inhibitors, have been most useful in controlling the reflux symptoms associated with Barrett's oesphagus, they have not reduced the incidence of adenocarcinoma of the oesphagus. The same can be said about anti-reflux surgery. Surgical excision of Barrett's oesphagus has been advocated when high-grade dysplasia is detected; this carries considerable morbidity and mortality, so alternative treatments are being developed.
This update summarises recent information concerning newer treatments aimed at eradicating Barrett's oesphagus. These vary from thermal coagulation (using electrocoagulation and heater probes) to lasers, photodynamic therapy and mechanical methods Of these, photodynamic therapy using a porphyrin precurser (5-ammo-laevulinic acid) seems to give the most consistent satisfactory results with a minimum of complications However, persistence of some metaplastic cells beneath the neo-squamous layer remains a problem. Ongoing effective acid control (by medical or surgical therapy) is also essential to prevent recurrence of Barrett's oesphagus. Future research is aimed at perfecting these methods. Ultimately, it may be possible to understand the molecular biology which could help to predict which patients are at greatest risk of developing dysplastic and carcinomatous changes
In the automotive industry the need for lower manufacturing costs, the use of fewer strategic materials, and the need for easier, faster, and more environmentally sound coating processes is growing. ...This has led to the examination of a plasma powder spray process used in the application of coatings for surface modification. The present paper examines the use of the plasma powder spray process in coating aluminium-silicon cylinder block bores using a rotating plasma gun capable of producing coatings of reliable microstructure and integrity. Properties and microstructures of the applied coatings are presented and test results show that the necessary bond strength of the coating can be achieved without the use of a bond coat. Surface preparation before coating and surface finishing methods after coating are also discussed. Experience in Europe, Japan, and the USA shows that the plasma powder spray process offers a performance proven and cost effective solution for the coating of cylinder bores.
Laser treatment was used to prepare substrate surfaces for thermal spray deposition. The interaction between aluminium and titanium alloys and short Nd: YAG laser pulses was investigated. In ...particular, the topography of laser treated surfaces has been observed and analysed using scanning electron microscopy, atomic force microscopy, and laser profilometry. The coating/substrate adhesion was quantified for various surface preparation parameters by means of tensile tests and Rockwell indentations for Al
2
O
3
-13 wt-%TiO
2
coatings. The influences of the laser energy density and the time interval between the laser treatment and the plasma spraying were studied. Compared with conventional degreasing and grit blasting, laser treatment produces better adhesion. The mechanisms of adhesion after laser treatment were investigated by transmission electron microscopy and electron energy loss spectrometry for a pure copper coating on a pure aluminium substrate. It appears that the adhesion is owing to metallurgical bonding.
In vitro somatostatin is a potent inhibitor of intestinal ion secretion in animal models and cultured human cell lines, providing a rationale for its use in secretory diarrheas. However, the effects ...of somatostatin on ion transport in native human colonic epithelium have not been reported. In this study the effects of somatostatin and octreotide on the basal short-circuit current and the cAMP- and Ca2+-stimulated short-circuit current were studied in isolated human colonic mucosa mounted in Ussing chambers. Under basal conditions somatostatin and octreotide (1 micromol/liter) stimulated a small, bumetanide-sensitive increase in short-circuit current. Following stimulation of secretion with prostaglandin E2, somatostatin and octreotide further increased the short-circuit current in a dose dependent fashion (ED50 approximately 10 nmol/liter for both). This stimulation of short-circuit current was not affected by pretreatment of the tissue with basolateral tetrodotoxin (1 micromol/liter) or mucosal amiloride (10 micromol/liter). In contrast, somatostatin and octreotide had no effect when secretion was stimulated with 8-bromo-cAMP, and pretreatment of the tissue with somatostatin and octreotide (0.1 micromol/liter) did not alter the secretory response to carbachol. The absence of any inhibitory effect of somatostatin and octreotide on electrogenic secretion in the human colon may explain the variable results obtained when somatostatin or octreotide are used for the treatment of secretory diarrheas.
Recent studies in a cultured model of the intestinal epithelium (HT-29cl.19A) have shown that somatostatin-14 (SS-14) inhibits the Cl- secretory process by acting at multiple G protein-dependent ...sites. These actions may underlie the antidiarrheal properties of SS peptides. This study has investigated the expression of specific SS receptor subtypes (SSTR) in HT-29cl.19A and examined their role in mediating SS antisecretory actions. Two predominant SSTR, SSTR1 and SSTR2, were identified by reverse transcriptase-polymerase chain reaction (RT-PCR) of mRNA from polarized HT-29cl.19A monolayers. Receptor binding studies showed evidence of two distinct populations of binding sites consistent with the known properties of SSTR1 and SSTR2. The role of SSTR in inhibition of secretion was investigated by comparing the effectiveness of native and synthetic SS peptides on adenosine 3',5'-cyclic monophosphate (cAMP)-dependent Cl- secretion. Secretion stimulated by the receptor-mediated agonist prostaglandin E2 (PGE2) was inhibited > 70% by SS-14 with a 50% effective concentration (EC50) of 32 nM. In contrast, SMS-201-995 (SMS) and RC-160 exhibited little or no antisecretory activity (maximum inhibition of 15 +/- 1.9 and 2.8 +/- 1.9%, respectively, at 100 microM; EC50 > 1.5 microM). Similar effects on PGE2-stimulated cAMP accumulation were also observed. SS-14, but not SMS, also inhibited secretion stimulated by dibutyryl cAMP, which acts independently of changes in cellular cAMP. Pretreatment with pertussis toxin reversed the antisecretory effects of SS peptides.
