Global control of meiotic recombination genes by Schizosaccharomyces pombe rec16 (rep1)

1. The influence of circulating 5-hydroxytryptamine (serotonin) on small intestinal motility was investigated in healthy volunteers. 2. Small intestinal motility was studied by means of a constantly perfused multi-channel manometry tube, connected to a computer system. 3. Intravenous infusions of either 5-hydroxytryptamine at increasing doses or saline were given over a period of 4 h. 4. 5-Hydroxytryptamine infusion dose-dependently increased plasma 5-hydroxytryptamine from approximately 2 to 10 and 25 nmol/l respectively, as well as urinary excretions of 5-hydroxytryptamine and 5-hydroxyindole acetic acid, a major 5-hydroxytryptamine metabolite. 5. The number of phase III of the migrating motor complex originating in the small intestine was dose-dependently increased by 5-hydroxytryptamine, and found to correlate to the plasma concentration of 5-hydroxytryptamine. The fraction of phase III also increased at the expense of phase II activity. In addition, 5-hydroxytryptamine increased the motility index, propagation velocity of phase III activity and the amplitude of contractions during phase III. 6. Whereas the low dose of 5-hydroxytryptamine (15 nmol.min-1.kg-1) had no haemodynamic effects, an increase in heart rate by approximately 20 beats/min, without change in blood pressure, was observed at the higher dose (60 nmol.min-1.kg-1). Respiratory parameters did not change during infusion of 5-hydroxytrytamine at either dose. 7. In conclusion, elevation of circulating 5-hydroxytryptamine by intravenous infusion results in more frequent and faster propagating migrating motor complexes in the human small intestine during the inter-digestive period.     

Chemoprevention of head and neck cancer

The role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the regulation of exocrine and endocrine pancreas was investigated in conscious sheep. Intravenous infusions of PACAP-27 and PACAP-38 (1, 3, and 10 pmol/kg/min) for 10 min during phase II of the duodenal migrating myoelectric complex accelerated pancreatic protein and amylase outputs dose-dependently. The responses in enzyme secretion to both PACAPs at the highest doses were inhibited significantly by atropine infusion (14.4 nmol/kg/min). Vasoactive intestinal polypeptide (VIP) at 3 pmol/kg/min significantly accelerated protein but not amylase outputs, although the response to the highest dose was not significantly influenced by atropine. PACAP-27 and VIP increased pancreatic juice flow and bicarbonate output dose-dependently; however, the responses to the highest dose were not altered significantly by atropine. On the other hand, intravenous injection of PACAP-38 (100 pmol/kg) did not influence basal plasma concentration of insulin, glucagon, and glucose. Moreover, PACAP-38 (1-100 pmol/kg) altered neither pancreatic endocrine response to intravenous infusion of glucose (20 mumol/kg/min) not that to n-butyric acid (33 mumol/kg/min). These results suggest that PACAP contributes to the regulation of exocrine secretion of the ovine pancreas but not to endocrine secretion. PACAP appears to accelerate pancreatic enzyme secretion mostly via the cholinergic nerves.     

Hydration and occlusive treatment of a sutured wound

BACKGROUND: The somatostatin analogue octreotide has been proposed as a possible therapeutic agent in patients with abnormal gastrointestinal motility. This study was conducted to study the effects of 0.5 microg/kg and 1.0 microg/kg subcutaneous octreotide on antroduodenal motility in children with chronic gastrointestinal disorders. METHODS: Twenty-three children were studied, eight with intestinal pseudo-obstruction, six with nonulcer dyspepsia, six with gastroesophageal reflux disease, and three with intractable constipation. After recording fasting motility for more than 4 hours, the children were randomized to receive 0.5 microg/kg or 1 microg/kg of subcutaneous octreotide. Motility was recorded for another hour after feeding in 12 children. RESULTS: Phase III of the motor migrating complex was present in 13 of 23 children before and in 21 after octreotide (p < 0.02). All phase III episodes after administration of octreotide except one originated in the small intestine. Phase IIIs after octreotide were longer and were propagated faster than the spontaneous phase IIIs. There were no antral contractions during fasting after octreotide. There was a significant decrease in phase II intestinal motor activity in the hour after administration of octreotide (p < 0.001). There was no difference in effect between the two doses. After feeding, antral contractions were present in all children, and intestinal phase IIIs were not abolished. CONCLUSIONS: In children with chronic bowel disorders, subcutaneous octreotide induced phase IIIs that differed from spontaneous phase IIIs and were not inhibited by meals. Octreotide decreased antral motility during fasting and inhibited intestinal phase II. Feeding abolished the inhibitory effect of octreotide on antral motility.     

Effect of octreotide on human sphincter of Oddi motility following liver transplantation

The effect of octreotide on sphincter of Oddi motility was investigated in six liver transplant patients, employing percutaneous (through the T-tube tract) manometry. Continuous and simultaneous sphincter of Oddi and duodenal motor activities were recorded before and for 60 min after the administration of octreotide (100 micrograms subcutaneously) and after the injection of cholecystokinin (0.02 microgram/kg intravenously). With octreotide, contraction frequency and basal pressure significantly increased (P < 0.05). This effect lasted more than 60 min, long after octreotide-induced duodenal migrating motor complex phase III activity had ceased. Sphincter of Oddi contraction amplitude and duration were unaffected by octreotide. Subsequent cholecystokinin administration transiently reduced sphincter of Oddi basal pressure and contraction frequency. We conclude that octreotide significantly increases sphincter of Oddi basal pressure and contraction frequency. This effect is distinct from octreotide induction of migrating motor complex phase III activity, persists for a prolonged period, and is inhibited by cholecystokinin.     

Endotoxin actions on myoelectric activity, transit, and neuropeptides in the gut. Role of nitric oxide

The lipopolysaccharide (endotoxin) of gram-negative bacteria has systemic effects in animals and man. Our aim was to investigate the effects of E. coli lipopolysaccharide on motility and transit through the small intestine in rats and to analyze plasma and tissue concentrations of intestinal neuropeptides. When lipopolysaccharide (20-160 micrograms/kg) was administered intravenously, the migrating myoelectric complex was replaced by spike bursts accompanied by rapid transit. Tissue concentrations of substance P and neurokinin A decreased, while plasma levels of calcitonin gene-related peptide increased N omega-Nitro-L-arginine, N omega-L-arginine methyl ester, dexamethasone, or indomethacin prevented these changes in myoelectric activity and tissue contents of neuropeptides. All of these compounds, except indomethacin, prevented the increased rate of transit. Thus, lipopolysaccharide changes motility through the nitric oxide and arachidonic pathways, resulting in rapid transit through the gut.     

Glucagon-like peptide-1 retards gastric emptying and small bowel transit in the rat: effect mediated through central or enteric nervous mechanisms

This study investigated effects of glucagon-like peptide-1(7-36)amide (GLP-1) on gastric emptying, small intestinal transit, and contractility of smooth muscle strips in rats. GLP-1 at doses of 10 and 20 pmol/kg/min administered intravenously dose-dependently retarded transit of the small intestine (P < 0.001), while only the higher dose of 20 pmol/kg/min retarded gastric emptying (P < 0.01). GLP-1 at concentrations up to 10(-4) M did not affect the basal tone or contractility of the gastrointestinal muscle strips that were stimulated with electric field stimulation or acetylcholine. Our results demonstrate that small intestinal transit seems more sensitive than gastric emptying to inhibition by GLP-1 at physiologic levels in plasma. Furthermore, this inhibition appears to be mediated through central mechanisms rather than through peripheral actions. Thus, GLP-1 is suggested to inhibit gastric emptying and small intestinal transit through an indirect effect via central or enteric nervous mechanisms.     

Two types of modified cardiac Na+ channels after cytosolic interventions at the alpha-subunit capable of removing Na+ inactivation

Repeated oesophageal acidification is a definitive feature of gastro-oesophageal reflux disease, which in turn is caused by relaxation of the lower oesophageal sphincter (LOS). This study in anaesthetised ferrets investigates the reflex pathways involved in effects of oesophageal acidification on motor function of the LOS, with particular focus on the role of tachykinins. LOS pressure was monitored with a perfused micromanometric sleeve assembly. Oesophageal acidification reduced LOS pressure by 48 +/- 5% until washout with saline. This reduction became larger with repeated tests, and was unaffected in amplitude by acute bilateral vagotomy, although the response became slower in onset. Intra-oesophageal capsaicin (0.5% solution) caused a 68 +/- 17% decrease in LOS pressure which remained unchanged with repeated tests. The NK-1 receptor antagonist CP96,345 (1-5 mg/kg intravenous (i.v.) blocked the post-vagotomy LOS responses to both intra-luminal acid and capsaicin. Close intra-arterial (i.a.) injections of capsaicin (1-100 micrograms) gut induced LOS relaxation which was neither vagally nor NK-1 receptor-mediated. Substance P or the selective NK-1 receptor agonist [Sar9, Met(O2)11] substance P (25-500 ng close i.a.) caused a biphasic LOS response, consisting of initial brief contraction followed by prolonged, dose-dependent relaxation. Tetrodotoxin (10 micrograms/kg close i.a.) changed the biphasic response to substance P to excitation only. The neurokinin-1 (NK-1) receptor antagonist CP96,345 (0.3-10 mg/kg i.v.) dose-dependently reduced the inhibitory response to substance P. The excitatory phase of the response to substance P was larger and prolonged after guanethidine (5 mg/kg, i.v.), or propranolol (1 mg/kg, i.v.). L-NAME (100 mg/kg i.v.) reduced the inhibitory phase. The selective NK-2 receptor agonist [beta-Ala8] neurokinin A(4-10) caused LOS excitation only. These data indicate that intra-oesophageal acid causes substance P release from extrinsic afferent nerve endings which activates local inhibitory pathways to the LOS via NK-1 receptors.     

Motilin induces gall bladder emptying and antral contractions in the fasted state in humans

BACKGROUND: Animal studies have shown that motilin affects gall bladder motility. In humans, no effect has been shown, but erythromycin, a motilin receptor agonist, induces gall bladder emptying. AIMS: To explore the effect of increasing doses of exogenous motilin on gall bladder volume and antral contractility in the fasted state in humans. METHODS: After an overnight fast, eight healthy men received increasing intravenous doses of Leu13-motilin (KW-5139) or 0.9% NaCl in a double blind, randomised fashion. Gall bladder volume and antral contraction frequency were determined by ultrasonography. RESULTS: Infusion of motilin increased plasma motilin levels. Motilin induced a reduction in gall bladder volume of 8.0 (5.0)%, 17.1 (5.0)%, 18.5 (4.7)%, and 16.1 (4.9)% of baseline volume at the end of infusion of 2, 4, 8, and 16 pmol/kg/min respectively, compared with mean stable gall bladder volumes during placebo infusion (p < 0.05). Antral contraction frequency increased during motilin infusion, but not during placebo infusion (p < 0.05). CONCLUSIONS: Exogenous motilin reducted fasting gall bladder volume and increased antral contractions. After reaching maximal reduction, the gall bladder volume did not decrease further during continuous motilin infusion at higher doses and stayed at the same reduced volume. The degree of gall bladder volume reduction during motilin infusion mimicked gall bladder emptying preceding antral phase III activity of the migrating motor complex in humans. This study indicates that motilin may play a physiological role in the regulation of gall bladder emptying in the fasted state.     

Dystonia

The need for extrinsic neural input to the upper gut in regulation/control of cyclic interdigestive motility and release of motilin remains a topic of controversy. Our aim was to determine whether extrinsic denervation of the upper gut disrupts cyclic release of motilin in relation to the migrating motor complex. Ten dogs underwent transection of all extrinsic innervation and enteric neural input to the stomach, small intestine, colon, pancreas, and liver while enteric neural continuity within this multivisceral complex was maintained. A cyclic pattern of motility occurred during fasting in all dogs in the small bowel (period = 100 +/- 3 min, mean +/- standard error of the mean) and in 8 of 10 dogs in the stomach (period = 98 +/- 4 min). Gastric cycles were temporally coordinated with small bowel cycles. Plasma motilin concentrations cycled temporally with the motility pattern with the greatest concentrations occurring during gastroduodenal phase III-like activity. Exogenous motilin induced a burst of gastric contractions and a premature migrating motor complex in all dogs. Oral meals disrupted cyclic motility and cyclic changes in plasma motilin. Extrinsic innervation to the upper gut is not necessary for cyclic motor activity, for coordinated cyclic release of motilin, or to initiate a premature migrating motor complex-like response to motilin. Central nervous system input (afferent, efferent) is not necessary for cyclic interdigestive activity or cyclic release of motilin.     

Manometry of the upper intestinal tract in patients with systemic sclerosis: a prospective study

OBJECTIVE: To assess both the prevalence and the characteristics of motor disorders of the small bowel in patients with systemic sclerosis (SSc) and to investigate for an association between clinical manifestations in the upper intestinal tract, capillaroscopic features, esophageal motor impairment, and manometric evidence of motor disturbances. METHODS: Fasting and postprandial motor activity of the upper intestinal tract was studied in 17 consecutive patients with SSc (6 with and 11 without clinical manifestations of small bowel involvement) and 17 age- and sex-matched healthy control subjects. RESULTS: The prevalence of manometric evidence of intestinal involvement was as high as 88% in the SSc patients; normal motor activity was present in only 2 patients. The median values for duodenal and jejunal interdigestive phase III migrating motor complex duration, amplitude, and velocity and the postprandial motility index were therefore lower in SSc patients compared with controls. Our manometric findings indicated that there are both neuropathic and myopathic stages of upper intestinal tract dysfunction in SSc. Furthermore, no association could be found between the severity of the intestinal manometric abnormalities and clinical presentation, SSc subsets, disease score, capillaroscopic findings, or esophageal manometric impairment. CONCLUSION: We suggest that manometry of the upper intestinal tract may be useful in SSc patients with clinical manifestations in the small bowel (i.e., malabsorption syndrome or pseudoobstruction) in that it can be used to accurately evaluate both the nature and the severity of motor disturbances. Furthermore, this procedure can be used to assist in the selection of patients who may require octreotide therapy.     

Clinical presentations and results of therapy of 63 acromegalic patients Chang Gung Memorial Hospital

The role of nitric oxide in inflammatory responses to substance P and other mediators of inflammation was examined in rat skin microvasculature in a blister base raised on the hind footpad. Superfusion of substance P (1 microM) over the blister base caused an increase in plasma extravasation and a vasodilator response which was not maintained. N(G)-Nitro-L-arginine (100 microM), an inhibitor of nitric oxide biosynthesis, attenuated vasodilatation and plasma extravasation due to substance P. The inactive isomer N(G)-nitro-D-arginine was without effect. Neurokinin A (1 microM), 5-hydroxytryptamine (1 microM), ATP (50 microM) and vasoactive intestinal polypeptide (1 microM) elicited vasodilation, which for vasoactive intestinal polypeptide was maintained even after washout. 5-Hydroxytryptamine and neurokinin A, but not ATP or vasoactive intestinal polypeptide, significantly increased plasma extravasation. Vasodilatation to neurokinin A, 5-hydroxytryptamine and ATP, and the increase in plasma extravasation due to neurokinin A and 5-hydroxytryptamine were unaffected by N(G)-nitro-L-arginine (100 microM), whereas vasodilation due to vasoactive intestinal polypeptide was significantly attenuated. These findings suggest that in rat skin microvasculature in vivo, nitric oxide is involved in vasodilator responses due to substance P and vasoactive intestinal polypeptide, and plasma extravasation due to substance P, but does not contribute significantly to vasodilatation induced by neurokinin A, 5-hydroxytryptamine or ATP, or the plasma extravasation induced by neurokinin A or 5-hydroxytryptamine.     

Differential effects of antimuscarinic agents on intestinal motility in the conscious dog

In this study we investigated the effects of antimuscarinics with different selectivity on the intestinal migrating myoelectric complex (MMC) in five fasting, conscious dogs, chronically fitted with electrodes along the small bowel. Furthermore, we evaluated the chronotropic and mydriatic effects to assess the in vivo selectivity of the agents tested. Dose-response studies were performed with the following drugs administered i.v.: atropine, telenzepine (M1 antagonist), AF-DX 116 [11,2-(diethylamino)methyl-1-piperidinyl-acetyl-5,11-dihydro-6H-pyrido-2 ,3b- 1,4-benzodiazepine-6-one (M2 antagonist)] and 4-diphenylacetoxy-N- methylpiperidine methiodide (4-DAMP) (M3 antagonist). All the antimuscarinics tested dose-dependently increased the duration of the MMC period and inhibited spike activity, except low-dose telenzepine (3-10 nmol/kg), which shortened the MMC period and stimulated spike activity. High-dose telenzepine (> 100 nmol/kg) mimicked the inhibitory effect of atropine on the intestine. ED50 values for delay of MMC onset were 87,232, > 10,000 and 129 nmol/kg for atropine, telenzepine, AF-DX 116 and 4-DAMP, respectively. At doses lengthening the MMC period, atropine and 4-DAMP also induced tachycardia and mydriasis. At doses shortening the MMC period, telenzepine had no effect on pupil diameter or heart rate, except at the dose of 10 nmol/kg, which reduced heart rate. Finally, AF-DX 116, at doses inducing marked tachycardia, had a minor intestinal effect and no mydriatic effect. The present data are consistent with the hypothesis that both M1 and M3 receptors are involved in the regulation of the MMC: M1 receptors are probably located on an inhibitory pathway, whereas M3 receptors mediate excitatory stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)     

Orthotopic liver transplantation improves small bowel motility disorders in cirrhotic patients

Altered small intestinal motility has been observed in patients with liver cirrhosis. Its pathophysiology remains to be defined. Our aim was to investigate the effect of orthotopic liver transplantation on small intestinal dysmotility in patients with liver disease. Two patients were studied both before and after orthotopic liver transplantation. Abnormal migrating motor complex activity and prominent clustered contractions present preoperatively normalized within 6 months after the surgical procedure. This finding might represent an additional benefit of liver transplantation considering that altered motility may be involved in bacterial overgrowth and infections observed in these patients.     

A method for simultaneous recording and assessment of gut contractions and relaxations in vivo

The normal gut exhibits both contractions and relaxation from a resting tonus. Pathological and pharmacological information may be gleaned from separate measurement of these activities. Methods for recording and analyzing gut contractions have been presented before. We present an extension to the methods, utilising simple foil strain gauges tested here in male Sprague-Dawley rats. Coupled with a computer-based data acquisition and analysis system, we could assess the relaxation and contraction waves recorded simultaneously and from different gut regions in vivo. In contrast with the antrum, where spontaneous motor activity consisted of low frequency relaxations and random contractions, spontaneous duodenal motility was patterned into periodic groups of intense activity interposed by periods of low amplitude, low frequency contractions and relaxations. This grouped activity was propagatory, reminiscent of migrating myoelectrical complexes. When challenged with the ulcerogen cysteamine-HCl (56 mg/100 g s.c.), only duodenal motor activity was affected. Moreover, this treatment had differential effects in the duodenum. Patterned motility was no longer distinguishable, and contraction frequency and amplitude were increased while relaxation amplitude was decreased. This method affords a particularly sensitive and more precise assessment of both contractile and relaxant motor activity in vivo, before and after drug treatment.     

Cardiovascular and behavioural effects of intracerebroventricularly administered tachykinin NK3 receptor antagonists in the conscious rat

1. In the conscious rat, three tachykinin NK3 receptor antagonists, namely SR142801 ((S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)pro pyl)-4-phenylpiperidin-4-yl)-N-methylacetamide), R820 (3-indolylcarbonyl-Hyp-Phg-N(Me)-Bzl) and R486 (H-Asp-Ser-Phe-Trp-beta-Ala-Leu-Met-NH2) were assessed against the intracerebroventricular (i.c.v.) effects induced by senktide, a selective NK3 receptor agonist, on mean arterial blood pressure (MAP), heart rate (HR) and motor behaviour. 2. Senktide (10-650 pmol per animal; i.c.v; n = 4-16) at the lowest dose caused a significant fall in MAP (-10 +/- 6 mmHg), while at the highest doses (100 and 650 pmol), senktide caused a rise in MAP (9 +/- 3 and 12 +/- 1 mmHg, respectively) when compared to vehicle. The intermediate doses (25 and 65 pmol) had no effect on MAP. The highest two doses caused a tachycardia of 62 +/- 15 and 88 +/- 8 beats min(-1), respectively. The dose of 65 pmol had a biphasic effect on HR, an initial bradycardia of 47 +/- 12 beats min(-1) followed by a tachycardia of 46 +/- 14 beats min(-1). The lowest doses caused either a rise of 52 +/- 10 beats min(-1) (25 pmol) or no effect (10 pmol) on HR. All doses of senktide caused similar increases in face washing, sniffing and wet dog shakes except at the dose of 100 pmol, when wet dog shakes were more than double those observed with the other doses. 3. The antagonist SR142801 (100 pmol -65 nmol per animal; i.c.v.; n = 6-8) caused increases in MAP at the highest two doses (6.5 and 65 nmol) while HR, dose-dependently, increased (23 +/- 6 to 118 +/- 26 beats min[-1]) and the onset dose-dependently decreased. The (R)-enantiomer, SR142806 (100 pmol - 65 nmol per animal; i.c.v.; n = 6-8) only caused rises in MAP (13 +/- 2 mmHg) and HR (69 +/- 11 beats min[-1]) at the highest dose. These drugs had no apparent effect on behaviour, except for the highest dose of SR142801 which increased sniffing. The antagonist R820 (650 pmol - 6.5 nmol per animal; i.c.v.; n = 6) had no effect on MAP or HR and only increased sniffing behaviour at 6.5 nmol. At 650 pmol (n = 6), R486 had no effect on any variable, but at 3.25 nmol, i.c.v. (n = 4) a delayed tachycardia and a significant increase in all behavioural variables were observed. 4. The cardiovascular responses induced by 6.5 nmol SR142801 and 25 pmol senktide were inhibited by R820 (6.5 nmol, 5 min earlier i.c.v.). In contrast, R820 failed to affect the central cardiovascular and behavioural responses induced by 10 pmol [Sar9, Met(O2)11]substance P, a NK1 receptor selective agonist. The senktide-induced behavioural changes were not inhibited by R820 (6.5 nmol, i.c.v.) while R486 (650 pmol, i.c.v.) blocked both the cardiovascular and behavioural responses to 25 pmol senktide. A mixture of antagonists for NK1 (RP67580; 6.5 nmol) and NK2 (SR48968; 6.5 nmol) receptors injected i.c.v. did not affect the cardiovascular response to SR142801. Cross-desensitization was shown between the central responses to SR142801 and senktide, but not between SR142801 and [Sar9, Met(O2)11]substance P. 5. The antagonists SR142801 and SR142806 (6.5-650 nmol kg(-1); n = 5-7), given i.v., did not evoke any cardiovascular or behavioural changes, except a delayed bradycardia for SR142806 (650 nmol kg[-1]), and also failed to inhibit the increase in MAP evoked by senktide (4 nmol kg(-1), i.v.). However, at the highest dose, both drugs slightly reduced the senktide-induced tachycardia. 6. Although the present data are consistent with the in vitro pharmacological bioassays and binding data, showing that SR142801 is a poor antagonist at rat peripheral NK3 receptors, they suggest that SR142801 has a partial agonist action at these receptors centrally. A separation of the cardiovascular and behavioural effects mediated by central NK3 receptor activation was achieved with SR142801 and R820 but not with R486. These results could be explained by the existence of NK3 receptor subtypes in the rat or by the differential activation and inhibition of the same receptor protein linked to the production of different second messengers. Differences in the pharmacokinetic or pharmacodynamic properties of the antagonists cannot be excluded at this time.     

Ovarian steroid modulation of neurokinin contents in hypothalamus, pituitary, trigeminal nucleus, and cervical spinal cord of the ovariectomized female rat

Ovariectomized rats were treated with estradiol benzoate (EB) and progesterone in conditions known to negatively and positively regulate gonadotropin secretion. Injection with EB decreased the plasma concentration of substance P at the time of the positive feed-back exerted by EB on gonadotropin secretion, while having no effect on the plasma concentration of neurokinin A. In the hypothalamus, EB injection enhanced the substance P and neurokinin A content, while progesterone reduced the substance P content. In the anterior pituitary, the substance P content was increased after progesterone, and this increase was blocked by EB. Conversely, in the posterior pituitary, the substance P content was reduced after progesterone, and this effect was enhanced by EB. In the trigeminal nucleus, the substance P content was increased after progesterone and EB, while only progesterone affected neurokinin A content. Finally, in the cervical spinal cord, the substance P and neurokinin A contents were reduced after EB. We conclude that neurokinin contents are controlled by ovarian steroids not only in the hypothalamo-pituitary complex but also in the trigeminal nucleus and the cervical spinal cord.     

Varicosities of the paravertebral plexus of veins associated with nocturnal spinal pain as imaged by magnetic resonance venography: a brief report

BACKGROUND: Non-cholinergic non-adrenergic neural mechanisms involving nerves containing NO have been shown to modulate smooth muscle in the gastrointestinal tract, and it has been suggested that release from tonic NO inhibition may be important in the regulation of cyclical fasting small intestinal motility. AIMS: To evaluate the role of NO mechanisms in the regulation of fasting small intestinal motor activity in humans using a specific NO synthase inhibitor, NG-monomethyl-L-arginine ( L-NMMA). METHODS: In seven healthy male volunteers, duodenal and jejunal pressures were measured for four hours with a nine lumen manometric catheter. Volunteers attended on four separate days on which they received an intravenous infusion either saline or L-NMMA (0.5, 2, or 4 mg/kg/h) in random order. Intravenous infusions began 10 minutes after completion of phase III of the migrating motor complex (MMC). RESULTS: The first episode of phase III activity occurred earlier after infusion of 2 and 4 mg/kg/h L-NMMA than after infusion of 0.5 mg/kg/h L-NMMA or saline (mean (95% confidence interval) 52 (36-68) and 57 (18-97) v 116 (69-193) and 145 (64-226) minutes respectively) with a resultant MMC cycle length of 82 (59-105) and 86 (46-126) v 132 (49-198) and 169 (98-240) minutes respectively. The total number of phase III activities during the four hour recording was increased (p<0.05) by L-NMMA at a dose of 4 mg/kg/h (2 (1-3)) but not at 2 mg/kg/h (1.5 (1-2)) or 0.5 mg/kg/h (1.3 (1-2)) compared with saline (1.3 (0.6-2)). L-NMMA had no effect on the duration, velocity, number of contractions per minute, length of migration, or site of origin of phase III of the MMC. The duration of phase I activity was shorter (p<0.05) with 4 mg/kg/h L-NMMA than with saline (12 (1-23) v 31 (19-44) minutes). CONCLUSIONS: These observations suggest that NO mechanisms play a role in the regulation of fasting small intestinal motor activity in humans.     

Severe late radiation enteropathy is characterized by impaired motility of proximal small intestine

Late radiation enteropathy (LRE) is a serious disorder, and therapeutic progress has thus far been hampered by insufficient understanding of the pathogenesis. This prospective study addresses whether alterations in proximal intestinal motility can predict the clinical severity of this disorder. Forty-one consecutive patients with chronic abdominal complaints after radiotherapy for gynecological cancer were examined by prolonged ambulatory manometry. Twenty-seven healthy adults served as controls. Impaired fasting motility was found in 12 of 41 patients (29%), and attenuated postprandial motor response after a liquid-solid meal was seen in 10 of 41 patients (24%). Postprandial delay of the migrating motor complex (MMC) was a good predictor of the degree of malnutrition (Cox regression, P < 0.01), and intensity of the MMC and postprandial motility index explained 69% (P < 0.001, multiple regression) of the variability in degree of malnutrition, assessed by weight loss and serum albumin level. The typical presentation of severe LRE was clinical symptoms suggesting intestinal pseudoobstruction, malnutrition, failure of a liquid-solid meal to induce postprandial motility, and delayed initiation and reduced intensity of MMC during nocturnal fasting. Prolonged ambulatory manometry was useful for detection of dysmotility in patients with symptoms of LRE and impaired motility of proximal small intestine seems to be a key factor in the pathogenesis of severe LRE.     

Activation of spinal N-methyl-D-aspartate or neurokinin receptors induces long-term potentiation of spinal C-fibre-evoked potentials

The use-dependent increase in synaptic strength between primary afferent C-fibres and second-order neurons in superficial spinal dorsal horn may be an important cellular mechanism underlying central hyperalgesia. This long-term potentiation can be blocked by antagonists of the N-methyl-D-aspartate subtype of glutamate receptor, the neurokinin 1 or the neurokinin 2 receptor. We have tested here whether activation of these receptors by superfusion of the spinal cord with corresponding agonists in the absence of presynaptic activity is sufficient to induce long-term potentiation. In urethane anaesthetized rats C-fibre-evoked field potentials were elicited in superficial laminae of lumbar spinal cord by electrical stimulation of the sciatic nerve. In rats with intact spinal cord, controlled superfusion of the spinal cord at recording segments for 60 min with N-methyl-D-aspartate, substance P or neurokinin A never induced long-term potentiation. Spinal superfusion with a mixture of N-methyl-D-aspartate, substance P and neurokinin A also failed to induce long-term potentiation in four rats tested. In spinalized rats, however, long-term potentiation was induced by either N-methyl-D-aspartate (at 10 microM, to 173 +/- 16% of control) substance P (at 10 microM, to 176 +/- 13% of control) or by neurokinin A (at 1 microM, to 198 +/- .20% of control). The induction of long-term potentiation by N-methyl-D-aspartate, substance P or neurokinin A was blocked by intravenous application of the receptor antagonists dizocilpine maleate (0.5 mg/kg), RP67580 (2 mg/kg) or SR48968 (0.2 mg/kg), respectively. Thus, activation of N-methyl-D-aspartate or neurokinin receptors may induce long-lasting plastic changes in synaptic transmission in afferent C-fibres and this effect may be prevented by tonic descending inhibition.     

Effect of ethanol on postprandial duodenojejunal motility in humans

The effect of ethanol on postprandial small bowel motility was investigated in eight healthy volunteers using perfusion of nutrient solutions (17% proteins, 59% carbohydrates, 24% lipids) into the descending duodenum (5 ml/min for 120 min). An ethanol-containing solution (4% w/v, 4.06 kcal/min, 1190 mosmol/kg) was compared with the corresponding ethanol-free solution (2.64 kcal/min, 160 mosmol/kg) and another ethanol-free hyperosmolar solution adapted in caloric load and osmolality (4.06 kcal/min, 1160 mosmol/kg). Motility was recorded with a data logger and six pressure transducers at 3-cm intervals around the duodenojejunal flexure. Clustered contractions (27 +/- 4/hr) migrating aborally through the whole recording segment were the predominant motor pattern with ethanol compared with the ethanol-free (10 +/- 2/hr; P < 0.01) and the ethanol-free hyperosmolar solution (6 +/- 3/hr; P < 0.001). Other motility parameters with ethanol were not different from the ethanol-free solution, whereas the ethanol-free hyperosmolar solution showed a much less intense motor response. We conclude that ethanol does modify human postprandial duodenojejunal motility by inducing propagative motor patterns.