Cerebral sites of central action of dermorphin on intestinal motility in the rat.

Dermorphin (DM), microinjected at 0.4 nmoles/rat into various sites of the periaqueductal gray matter (PAG), provokes complete inhibition of intestinal propulsion always coupled with full analgesia and catalepsy. When electrolytic lesions were made in the raphe magnus nucleus (NRM) a slight but significant reduction of intestinal inhibition evoked by DM into the PAG was observed. In contrast, pretreatment into the NRM 10 days before DM with a selective antiserotoninergic agent (5,6 DHT 15 microgram/rat), did not influence intestinal inhibition. As expected, both lesions reduced DM-induced analgesia but catalepsy was not affected. DM-induced inhibition of intestinal transit was therefore unaffected by subdiaphragmatic vagotomy. Finally, some other central brain regions were found sensitive to DM for the above effects such as the lateral and medial hypothalamus and mid-line thalamus. Negative results were obtained for the supraoptic nuclei and postero-medial cortical amygdaloid nucleus. Some considerations are put forward about the existence in the central nervous system of selective areas involved in intestinal modulation and their relationship with those mediating other opiate behavioural effects.

Central pharmacological activities and opiate receptor binding studies of some dermorphin analogs.

A series of dermorphin-like compounds were injected intracerebroventricularly in the rat to assess in vivo their effects on intestinal motility and analgesia. In vitro they were tested by binding assay using 3H-naloxone as radioligand or by guinea pig ileum bioassay. The synthetic peptides were less potent than dermorphin in inhibiting intestinal transit and in producing analgesia, or even inactive up to doses 30 times the dermorphin ED50. This reduction in pharmacological activity was coupled with a decrease in binding potency. The 3H-naloxone binding studies in the absence or presence of Na+ indicated that Na+ reduced the interaction of dermorphin and its analogs with brain opiate receptors. Only the dibenzyl derivative was slightly affected by sodium, suggesting a dual action for this peptide, as confirmed by preliminary data from guinea pig ileum bioassay.

Central and peripheral components of dermorphin's effect on rat intestinal propulsion in comparison to morphine.

Dermorphin, injected intracerebroventricularly (ICV) to rats, provokes, like to morphine, an inhibition of intestinal propulsion linearly related to the log of the administered doses (in the range from 0.06 to 0.56 micrograms/rat), but it is 143 times more active than morphine. Naloxone, ICV or IP, antagonizes dermorphin less effectively than morphine. Quaternary naloxone ICV administered antagonizes the intestinal effect of ICV dermorphin, while IP administered it is not effective until 8 mg/kg. The dose of dermorphin maximally active by the ICV route (0.56 micrograms/rat) is completely inactive when injected IP. Increasing doses of dermorphin IP (from 12 to 6400 micrograms/kg) inhibit intestinal propulsion to the same extent irrespectively of the doses employed, but never by more than 50%. Only a high dose of naloxone (30 mg/kg/IP) antagonizes this IP effect. The central and peripheral components of this intestinal effect of dermorphin are discussed.

Dermorphin interaction with peripheral opioid receptors.

The interaction of dermorphin with different peripheral opioid receptor subtypes was investigated in vitro, using the guinea pig ileum as representative tissue for mu, the mouse vas deferens for delta, the rabbit vas deferens for kappa and the rat vas deferens for epsilon. The effect of dermorphin on each tissue preparation was compared with that of selective mu, delta, kappa epsilon agonists respectively morphine, met-enkephalinamide, ethylketocyclazocine and camel beta-endorphin. Antagonism with naloxone was also tested and calculated as Ke. It is concluded that dermorphin mainly interacts with the mu receptors, although it also binds to epsilon receptors; the interaction with delta receptors is questionable, and the kappa receptors are unaffected.

Intestinal effect and analgesia: evidence for different involvement of opioid receptor subtypes in periaqueductal gray matter.

Periaqueductal gray matter (PAG) has been shown to be one of the sites in the central nervous system where microinjections of morphine strongly inhibit intestinal transit. To investigate the nature of opioid receptor populations involved in this central effect, selective opioid agonists, FK 33824 for mu, DALA for delta, dynorphin for kappa and tentatively beta-endorphin for epsilon, were microinjected in all PAG areas previously identified as morphine-sensitive for intestinal inhibition. The PAG-induced inhibition of intestinal transit appears to be mediated mainly by mu receptors and possibly by epsilon receptors. kappa and delta receptors seem not to be involved.

Involvement of periaqueductal gray matter in intestinal effect of centrally administered morphine.

Microinjections of morphine in the rat periaqueductal gray matter (PAG) inhibited intestinal transit in linear relation to the log of the dose administered (in the range from 5 to 20 micrograms/rat). This linear regression was parallel with that obtained on intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) administration of morphine and the intracerebral (i.c.) route was calculated to be 4 times more potent than the i.c.v. route and 189 times more potent than the i.p. route. Monolateral electrolytic lesions into the PAG abolished the intestinal effect of i.c.v. morphine to a large extent. The relevance of other brain areas and the type of opiate receptors involved in this central effect of morphine are discussed.

Effect on intestinal transit of neurotensin administered intracerebroventricularly to rats.

Neurotensin (NT) administered intracerebroventricularly (i.c.v.) to rats, blocks intestinal transit (tested by charcoal meal) in linear relation to the log of the doses within the range of 0.6-2.5 nmoles/rat. NT in this test is about 40 times more active than morphine (M) and 6 times less active than dermorphin (DM) on a molar basis. Within this dose range NT does not induce analgesia (tail-flick test) or hypothermia (tested at 22 degrees C). The intestinal effect can also be elicited by injecting the peptide into the periaqueductal gray matter (PAG). NT injected intraperitoneally (i.p.) is inactive up to doses 4 times the maximal active i.c.v. dose. Naloxone (Nx) and dynorphin 1-13 could not antagonize the intestinal effect of i.c.v. NT. The relationship between this central intestinal effect and many other central effects of NT is discussed.

Continuous on-line determination of recirculation by thermodilution in hemodialysis patients.

The consistency of the determination of A-V fistula recirculation (R) using the thermodilution method (T) with a new probe (blood temperature monitor, BTM Fresenius A.G.) was studied in 32 patients (AVF: proximal 34%, distal 63%, graft 3%). We compared R calculated by T with both the traditional three-sample method (C) and the low-flow three-sample method (L); both BUN and creatinine (CR) were measured in all samples at the beginning and at the end of the session. T was also determined at the 2nd and 3rd hour. There was a significant correlation between T and either C or L at the start of the session (BUN and CR) as well as at the end (only CR). R was higher (11.9 +/- 10) in proximal AVF than in the distal (5 +/- 3.1%; p0.01) when measured by T at the same blood flow (QB: 313 +/- 45 vs 343 +/- 52 mls/min, p = ns). T increased but not significantly by increasing Qb from 150 to 300 mls/min in ten patients. No correlation was found during the session between blood pressure and T variations. In conclusion, T and L give very similar results while C overestimates recirculation. R is easy to perform repeteadly by T with results available online.

[Lithiasis of the common bile duct and transduodenal papillosphincterotomy. Analysis of our cases]. / Litiasi della via biliare principale e papillosfinterotomia transduodenale. Analisi della nostra casistica.

The results obtained from 1978 to 1987 with the use of transduodenal papillosphincterotomy in bile duct lithiasis are reported. The operation was performed on 126 patients and produced 4.7% immediate mortality. The indications and the most frequent post-operative complications were studied. Routine intra-operative cholangiography had been carried out. The long-term results were very good in 86% of the cases, average in 13% and poor in 1%. Provided one limits its indications to cases when it is really necessary, papillosphincterotomy does not involve a higher risk than other biliary operations.

[Truncal vagotomy and cholelithiasis]. / Vagotomia tronculare e colelitiasi.

A group of 50 patients with total vagotomy plus pylorolasty are studied with pre and postoperative cholecystography in a four years follow-up. 50 patients with parietal cell vagotomy (selective vagotomy) served as control group. The AA. study the correlation of gallbladder dilatation with gallstones formation after total vagotomy. On the contrary parietal cell vagotomy prevents these dysfunctions.

[Percutaneous drainage of liver abscesses]. / Il drenaggio percutaneo degli ascessi epatici.

Three patients with hepatic abscess were treated by percutaneous drainage ultrasonographically or tomographically guided. The treatment was effective in two out of three patients. The low morbidity and the high success rate obtained suggest that this therapeutic modality should be used before considering any surgical approach.

[Non-parasitic splenic cyst]. / Le cisti spleniche non parassitarie.

The Authors report a case of epithelial cyst of the spleen. The pathogenetic hypothesis as well as the clinical patterns of this rare disease, which is usually found in children and young adults, are considered.

The direct demonstration of binding of mu, delta and kappa agonists to digitonin-solubilized opioid receptors from bovine striatum.

Active opioid binding sites, that retain the ability to bind tritiated agonists have been obtained in good yield in digitonin/NaCl/Mg2+ extracts of morphine protected bovine striatal membranes. Ligand protection of binding sites and the presence of Mg ions were found to be absolute requirements for agonist binding in this solubilized opioid receptor preparation. Soluble preparations contained a ratio of mu: delta:kappa similar to that in the membranes.

Theophylline pharmacokinetics and liver function indexes in chronic liver disease.

Since patients with chronic liver disease present with greatly varying theophylline disposal reductions, in cirrhotics the acute theophylline dose schedule must be guided by an index of liver function that predicts theophylline pharmacokinetics. We therefore studied 26 patients with severe chronic liver disease to ascertain the efficacy of the routinely used clinical and biochemical liver function tests in predicting theophylline pharmacokinetics. The prealbumin plasma level, recently proposed as a valuable index of liver function, was also considered. With respect to 10 controls, theophylline clearance was found to be significantly reduced (30 +/- 2 vs. 75 +/- 11 ml/kg/h, mean +/- SD, p less than 0.01). However, only 7 patients had a reduction great enough to require a reduced intravenous theophylline dose schedule. An analysis of clinical utility, made on the basis of ROC curves, showed that the albumin/globulin ratio was the most effective index for identifying patients requiring lower doses of theophylline. Prealbumin and albumin were also useful, whereas bilirubin, prothrombin time, pseudocholinesterase, the presence of ascites and Pugh-Child's classification of the severity of liver disease were found to be worthless.