Search PubMed⌕ Search

Biomedical subjects

H Harling

Publications and source records attributed to H Harling.

At least 37 records · Page 2Linked to original sources
PubMed1993

Regulation of secretion of pancreatic spasmolytic polypeptide from porcine pancreas.

We studied the neural and hormonal regulation of the secretion of pancreatic spasmolytic polypeptide (PSP), a potential growth factor, from isolated perfused porcine pancreas and the pancreatic exocrine secretion of PSP in response to a meal in young conscious pigs. PSP concentrations in the pancreatic juice ranged from 1 to 180 micrograms/ml. PSP released to the venous effluent amounted to 0.4-7% of the total output. Thus PSP is predominantly an exocrine product. Electrical vagal nerve stimulation increased PSP output 30-fold. Acetylcholine mimicked the effect of nerve stimulation, which was inhibited but not abolished by atropine. Both vasoactive intestinal polypeptide and gastrin-releasing peptide stimulated PSP secretion. PSP concentration in the juice decreased in response to secretin and increased after cholecystokinin octapeptide (CCK-8), but both increased PSP output. In conscious pigs, pancreatic secretion of protein and PSP increased in parallel. Like pancreatic enzyme secretion, we conclude that PSP secretion is controlled by parasympathetic mechanisms that include both cholinergic and peptidergic pathways and by endocrine mechanisms that may include both secretin and CCK-8.

Animals↗
PubMed1992

Extrinsic control of the release of galanin and VIP from intrinsic nerves of isolated, perfused, porcine ileum.

By immunohistochemistry galanin-like immunoreactivity and vasoactive intestinal polypeptide (VIP)-like immunoreactivity were found in nerve cell bodies mostly in the submucous plexus and in nerve fibres in the mucosa, submucosa and muscularis including the myenteric plexus of the porcine ileum and were found to co-exist in most of these structures. Using isolated, perfused porcine ileum we studied the release of galanin and VIP in response to electrical stimulation of the mixed periarterial nerves or to intraarterial infusions of different neuroactive agents. Nerve stimulation (4-10 Hz) inhibited the basal release of galanin and VIP from the ileum (to 69 +/- 6 and 62 +/- 6% of basal release). After infusion of the alpha-adrenergic blocker, phentolamine, (10(-6) M) electrical stimulation increased the release of both galanin and VIP (to 140 +/- 12 and 133 +/- 13% of basal output). This increase was abolished by atropine (10(-6) M) and by hexamethonium (3.10(-5) M). Infusion of norepinephrine (10(-6) M) inhibited, whereas acetylcholine (10(-6) M) stimulated the release of both peptides. The effect of the latter was abolished by atropine. The inhibitory effect of nerve stimulation was not influenced by atropine. Our results suggest that the galanin- and VIP-producing intrinsic neurons receive inhibitory signals by noradrenergic nerve fibers and stimulatory signals mediated by cholinergic nerves, possibly via a cholinergic interneuron.

Acetylcholine↗
PubMed1992

Circulating galanin: origin, metabolism, and pharmacokinetics in anesthetized pigs.

The concentration of galanin-like immunoreactivity (GAL-LI) was 12.9 +/- 0.9 pmol/l in porcine arterial plasma (n = 9) and ranged from 1 to 14 pmol/g in extracts of porcine gastrointestinal tract (n = 5), the colon being the richest gut segment. A significant (P less than 0.05) arteriovenous concentration difference of circulating endogenous GAL-LI occurred across the kidney (15.1 +/- 2.3 vs. 6.2 +/- 0.5 pmol/l) and a hind leg (15.7 +/- 2.5 vs. 10.2 +/- 1.0 pmol/l), whereas a negative gradient was observed across the intestine (12.5 +/- 2.0 vs. 17.7 +/- 3.3 pmol/l) of anesthetized pigs. Passage through the brain, liver, or lungs did not change the concentration of endogenous GAL-LI significantly. During basal circumstances, the major source of circulating GAL-LI is therefore the gut. During infusion of 20 pmol.kg-1.min-1 of synthetic porcine galanin, a significant extraction occurred across the kidney (64.8 +/- 4.3%), hind leg (20.3 +/- 3.8%), and liver (19.7 +/- 4.3%). The overall metabolic clearance rate was 37.8 +/- 3.7 ml.min-1.kg-1. The half-life of galanin in plasma was 4.6 +/- 0.3 min, and the apparent distribution space was 255.6 +/- 31.4 ml/kg. Incubation studies in vitro showed that the concentration of galanin, added to blood and plasma at 37 degrees C, was halved in 1 h, unless stabilized with EDTA and aprotinin.

Anesthesia↗
PubMed1992

Calcitonin gene-related peptide: effect on contractile activity and luminal cross-sectional area in the isolated, perfused porcine ileum.

Because calcitonin gene-related peptide (CGRP) is an abundant peptide in the enteric nervous system we studied the effect of intra-arterial infusions of synthetic human CGRP I in concentrations from 10(-10) to 10(-8) mol/l on contractile activity and luminal cross-sectional area in the isolated perfused porcine ileum, using manometry and impedance planimetry. The frequency of the basal contractile activity was 0.37 +/- 0.1 contractions per minute. CGRP induced phasic contractions, which at the highest dose were superimposed on tonic contractions, as determined by measurement of luminal cross-sectional area. The frequency of contractions dose-dependently increased to approximately 10/min at 10(-8) mol/l CGRP. The amplitude of contractions increased from a maximum of 35 cm H2O to 51 +/- 3 at 5 x 10(-9) mol/l CGRP and 52 +/- 6 cm H2O at 10(-8) mol/l CGRP. After the termination of CGRP infusion at the highest dose a short phase of up to 5 min with strong tonic contraction was observed. No phasic activity was detected by manometry during this phase. In conclusion, CGRP dose-dependently increased contractile activity in the pig ileum. CGRP may therefore participate in the regulation of small-intestinal motility in the pig.

Animals↗
PubMed1991

Fate of the rectum after colectomy and ileostomy for Crohn's colitis.

Eighty-four patients had colectomy with ileostomy and oversewing of the rectum for Crohn's colitis. Seventy-two patients were operated on because of intractable disease, colitis in combination with rectal fistulas, and toxic megacolon. The operative mortality was 6 percent, and neither emergency surgery nor treatment with steroids correlated with operative morbidity. After a median 7.7 years of follow-up, 25 ileorectal anastomoses had been undertaken, 16 of which were successful. Twenty-nine protectomies were performed; the resulting 10-year cumulative risk of proctectomy was 50 percent. While the risk of proctectomy was significantly less among patients with a normal rectum at colectomy compared with patients with proctitis, the initial macroscopic degree of proctitis did not correlate with the risk of subsequent proctectomy. The 5-year cumulative ileal resection rate in 29 patients with a rectum in situ but out of circuit was 29 percent. The possibility of a future ileorectal anastomosis should still be considered in patients with proctocolitis.

Adolescent↗
PubMed1991

Release of galanin from isolated perfused porcine adrenal glands: role of splanchnic nerves.

We found a high concentration of galanin in extracts of porcine adrenal glands (114 pmol/g). By immunohistochemistry, galanin was localized to groups of medullary cells previously shown to produce norepinephrine. To study mechanisms for the release of galanin, we developed the following in vitro model: isolated perfused porcine adrenals with intact splanchnic nerve supply. When the nerves were electrically stimulated, epinephrine and norepinephrine secretion increased 276- and 291-fold, respectively, and galanin release increased up to 1,300-fold. Acetylcholine at 10(-6) M stimulated galanin release, and hexamethonium almost abolished the response to nerve stimulation. Galanin infusions had no effect on epinephrine and norepinephrine secretion in concentrations of 10(-8) and 10(-7) M, but increased both cortisol and aldosterone secretion (P less than 0.05). Splanchnic nerve stimulation in anesthetized pigs increased the concentration of galanin in the caval vein but not in arterial plasma. It is concluded that galanin, coreleased with catecholamines from the adrenal glands, may have endocrine functions but that galanin may also have local regulatory functions in the adrenals.

Acetylcholine↗
PubMed1991

Distribution and effect of galanin on gallbladder and sphincter of Oddi motility in the pig.

This study was designed to determine the occurrence and topographical distribution of galanin-like immunoreactivity (GAL-LI) in the porcine gallbladder and sphincter of Oddi and to investigate the pharmacologic effect of GAL on gallbladder and sphincter of Oddi motility. By radioimmunoassay the concentration of GAL-LI in the gallbladder was 2.75 +/- 0.23, 9.73 +/- 1.33 in the common bile duct and 5.10 +/- 0.37 in the sphincter of Oddi (pmol/g +/- SE). By immunohistochemistry GAL-LI was found exclusively in ganglionic cells and in nerve fibers among the smooth muscle bundles. Gallbladder and sphincter of Oddi pressures were recorded before and during 5-minute local intraarterial infusion of 4, 8, 19, 39, 78 and 194 ng GAL - Kg-1 - min-1 in 12 anaesthetized pigs. GAL in doses greater than or equal to 39 ng.kg-1.min-1 significantly reduced sphincter of Oddi phasic wave frequency (4.8 +/- 0.4 vs. 2.1 +/- 0.5; p = 0.004) and sphincter of Oddi motility index (70.2 +/- 6.02 vs. 27.7 +/- 8.3; p = 0.002) but did not affect gallbladder pressure. We conclude that the distribution of GAL-LI in the sphincter of Oddi and the effect that a pharmacologic dose of GAL has on sphincter of Oddi motor activity, suggests that GAL may be involved in the physiologic control of bile flow in the pig.

Animals↗
PubMed1991

Galanin and vasoactive intestinal polypeptide: coexistence and corelease from the vascularly perfused pig ileum during distension and chemical stimulation of the mucosa.

By immunohistochemistry and double staining technique, almost complete coexistence of galanin-like immunoreactivity (GAL-LI) and vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) was demonstrated in submucosal ganglionic cells and mucosal nerve fibers of the porcine ileum. The release of the two neuropeptides was studied in isolated, vascularly perfused pig ileum. Distension (increasing intraluminal pressure by 10 mm Hg) and intraluminal instillation of homologous gallbladder bile, amino acids, 0.1 M HCl, hypertonic NaCl (3,400 mosm x kg-1) and hypertonic glucose (1,100 mosm x kg-1) all increased the release of GAL-LI and VIP-LI into the venous effluent in parallel. Being the most potent stimulus, bile increased the output of GAL-LI from 0.74 +/- 0.12 to 2.44 +/- 0.81 pmol/min (mean +/- SE, p = 0.018) and the output of VIP-LI from 3.29 +/- 0.19 to 12.68 +/- 4.01 pmol/min (p less than 0.001), respectively. In conclusion, the coexistence and parallel release of GAL and VIP suggest that GAL/VIP neurons may be involved in intramural secretory and motor reflexes.

Animals↗
PubMed1990

Galanin in the porcine pancreas.

Galanin, a 29 amino acid neuropeptide, was recently isolated from pig intestine. We studied the localization, nature and effect of galanin in pig pancreas. Galanin immunoreactive nerve fibers were regularly found in the pancreas. A peptide chromatographically similar to synthetic galanin was identified in pancreas extracts. The effect of galanin on the endocrine and exocrine secretion was studied in isolated pancreases, perfused with a synthetic medium containing 3.5, 5 or 8 mmol/l glucose and synthetic galanin (10(-10)-10(-8) mol/l). There was no effect on the basal exocrine secretion. The output of insulin, glucagon, somatostatin and pancreatic polypeptide (PP) was measured in the effluent. There was no effect on PP secretion. At a perfusate glucose concentration of 5 mmol/l, galanin at 10(-9) mol/l increased insulin secretion by 55 +/- 14% (mean +/- S.E.M., n = 5) of basal secretion, and at 10(-8) mol/l by 58 +/- 27% (n = 6). At 8 mmol/l glucose, insulin secretion increased by 25 +/- 10% (n = 6) and 62 +/- 17% (n = 8). At 5 mmol/l glucose glucagon secretion was increased by 15 +/- 3% (n = 5) by galanin at 10(-9) mol/l and by 29 +/- 11% (n = 5) by galanin at 10(-8) mol/l, and at 8 mmol/l glucose by 66 +/- 27% and 41 +/- 25%. Somatostatin secretion was inhibited to 72 +/- 2% (n = 5) of basal secretion by galanin at 10(-9) mol/l and to 65 +/- 7% (n = 7) at galanin at 10(-8) mol/l, both at 5 mmol/l glucose. At 8 mmol/l the figures were 83 +/- 6% and 70 +/- 10%. Insulin secretion in response to square wave increases in glucose concentration from 3.5 to 11 mmol/l (n = 5) increased 2-fold during simultaneous perfusion with galanin (10(-8) mol/l).

Animals↗
PubMed1990

Porcine pancreastatin has no effect on endocrine secretion from the pig pancreas.

We investigated the effects of porcine pancreastatin on the endocrine and unstimulated exocrine secretion of isolated, perfused porcine pancreas. Pancreastatin in a concentration of 10(-8) mol/l had no effect on basal secretion of insulin, glucagon and somatostatin at a perfusate glucose concentration of 5 mmol/l (n = 4) and neither at 10(-8) nor 10(-7) mol/l influenced the hormone responses to acute elevations of perfusate glucose concentration from 3.5 to 11 mmol/l (n = 7). This elevation strongly stimulated insulin secretion and inhibited glucagon secretion. Exocrine secretion was not affected by pancreastatin. The results suggest that pancreastatin does not directly influence pancreatic secretion.

Animals↗
PubMed1990

Pancreatic spasmolytic polypeptide, a potential growth factor for the intestine: neural control of secretion.

We studied the effect of electrical stimulation of the vagus nerves and the effect of vasoactive intestinal polypeptide (VIP) on the secretion of pancreatic spasmolytic polypeptide (PSP) from isolated perfused porcine pancreas. We measured the concentration of PSP in the pancreatic juice and in the venous effluent by radioimmunoassay. The concentration in the pancreatic juice varied between 1 and 180 micrograms/ml, and in the venous effluent between 1 and 10 ng/ml. PSP is thus mainly an exocrine product. However, the concentrations in juice and venous effluent varied in parallel. Electrical vagus stimulation increased the output in the juice of PSP approximately 30 times. Atropine (10(-6) M) prevented the increase in PSP concentration during vagus stimulation, but only partially inhibited the output. VIP (10(-8) M) increased the output of PSP but decreased the concentration. We conclude from these results that PSP secretion is controlled by neural parasympathetic mechanisms that include both cholinergic and peptidergic pathways.

Animals↗
PubMed1990

Galanin: distribution and effect on contractile activity and release of vasoactive intestinal polypeptide from the isolated perfused porcine ileum.

In the pig ileum galanin (GAL)-like immunoreactivity was identified in nerve cell bodies of the submucous plexus and in nerve fibers of the circular and longitudinal muscle layer. Infusion of 5.10(-10)-10(-8) M of GAL into the arterial line of the isolated perfused porcine ileum decreased the frequency of spontaneous phasic contractions in a dose-dependent manner. The frequency of phasic contractions during maximal inhibition by GAL 10(-8) M was 13 +/- 4% (mean +/- SE) of basal frequency (p less than 0.05). The recovery from inhibition by GAL 10(-8) M lasted 16 +/- 1 min. Tonic contractions were not observed in this experimental set-up, neither by standard perfused catheter manometry nor by measurement of cross-sectional area of an intraluminally located balloon. Infusion of GAL 10(-8) M decreased the venous release of vasoactive intestinal polypeptide to 80 +/- 8% of basal release (p less than 0.05). It is concluded that GAL may participate in the regulation of small intestinal motility in the pig.

Animals↗
PubMed1990

Identification of the neurotransmitter/neuromodulator functions of the neuropeptide gastrin-releasing peptide in the porcine antrum, using the antagonist (Leu13-psi-CH2 NH-Leu14)-bombesin.

We studied the effects of a new bombesin/gastrin-releasing peptide (GRP) receptor antagonist, Leu13-psi-(CH2NH)-Leu14-bombesin, on the secretion of gastrin and somatostatin and on the motor activity of isolated perfused porcine antrum in response to infusions of GRP at 10(-10) or 10(-9) mol/l and in response to electric stimulation of the vagus nerves. GRP significantly increased the secretion of gastrin and somatostatin and increased the frequency of antral contractions threefold. At 0.5 x 10(-6) mol/l the antagonist completely abolished the effects on motality and gastrin secretion and strongly inhibited the effect on somatostatin secretion. Vagus stimulation significantly increased gastrin and somatostatin secretion and increased the contraction frequency threefold. The antagonist strongly inhibited the somatostatin response, abolished the motility effects and reversed the stimulatory effect on gastrin secretion to a significant inhibition. Assuming that the antagonist interacts specifically with GRP receptors, we conclude that our data strongly support the concept that GRP-producing nerves are essential for vagally induced secretion of gastrin and somatostatin from the antrum. The GRP nerves may also play a role in the control of gastric motor activity.

Animals↗
PubMed1989

The natural history of symptomatic haemorrhoids.

In order to calculate the prognosis for a person who has developed a first episode of second degree haemorrhoids, 186 patients were randomly assigned to either no active treatment (expectant management) (n = 91) or rubber band ligation (n = 98) and reviewed every 6 months. The median follow-up period was 48 months in both groups with a range from 6-48 months in the banding group and from 18-48 months in the expectant management group. Rubber band ligation was performed at most three times with three weekly intervals. There were 6 treatment failures in the banding group in contrast to 31 in the expectant management group (p less than 0.01). The calculated recurrence rate by actuarial analysis among patients initially cured by rubber band ligation was 33% (95% confidence limits: 23-45) at four years and 61% (95% confidence limits: 48-74) in the expectant management group (p less than 0.05). It is concluded that rubber band ligation of symptomatic second degree haemorrhoids in up to three single treatments at three weekly intervals at the time of diagnosis significantly altered the prognosis without causing significant morbidity. However, 25% of the patients treated by expectant management never developed another episode during the four years observation time.

Adult↗
PubMed1989

Occurrence, distribution and motor effects of galanin in the porcine lower esophageal sphincter.

Specimens from the lower esophageal sphincter (LES) region of the pig were analyzed for galanin-like immunoreactivity (GAL-LI) using radioimmunoassay and immunohistochemistry. The mean concentration of GAL-LI was 3.4 pmol/g tissue. GAL-LI nerve fibers were observed surrounding muscle bundles in the smooth circular muscle layer, and in ganglion cells of the myenteric plexus. Bolus injection of 40-200 pmol/kg of galanin directly into the arterial supply of the resting LES increased the LES pressure (LESP) dose-dependently, whereas slow infusion of 2-100 pmol galanin/kg/min had no effect on resting LESP. The vagally increased LESP was not modulated by simultaneous galanin infusion, and the concentration of galanin in the venous effluent of the LES declined insignificantly during vagal stimulation. It is concluded that galanin may be an important neuropeptide for the modulation of resting LES tone.

Animals↗
PubMed1988

Naturally occurring products of proglucagon 111-160 in the porcine and human small intestine.

Recent studies have revealed that the glucagon gene is expressed in the mammalian intestine. Here it codes for "glicentin" (proglucagon 1-69) and a glucagon-like peptide, proglucagon 78-107, recently isolated from porcine intestine. We studied the fate of the remaining COOH-terminal part of proglucagon (proglucagon 111-160) using radioimmunoassays against proglucagon 111-123 and 126-160. Two peptides were isolated from acid ethanol extracts of porcine ileal mucosa and sequenced: one corresponding to proglucagon 126-158 and one probably corresponding to proglucagon 111-158. By comparing human and porcine proglucagon sequences, Ala117 is replaced by Thr, and Ile138, Ala144, Ile152 and Gln153 are replaced by Val, Thr, Leu, and His. By gel filtration and radioimmunoassay of intestinal extracts it was established that a large part of porcine and virtually all of human proglucagon are processed to release proglucagon 111-123 (designated spacer peptide 2), which, like proglucagon 126-158 must be considered a potential hormonal entity. By isocratic high pressure liquid chromatography human spacer peptide 2 was indistinguishable from synthetic proglucagon 111-122 amide, suggesting that this is the structure of the naturally occurring human peptide.

Amino Acid Sequence↗
PubMed1988

Prognosis after simple incision and drainage for a first-episode acute pilonidal abscess.

During a 3-year period 73 patients were treated consecutively for a first-episode acute pilonidal abscess with simple incision and drainage under local anaesthesia. In all cases the treatment relieved symptoms and all patients returned to work immediately after treatment. Healing per primam occurred in 42 patients (58 per cent; 95 per cent confidence limits: 45-69) within 10 weeks after treatment. These patients had significantly fewer pits and lateral tracts compared with patients who developed excessive granulation tissue after incision and who required definitive surgical treatment later. Nine patients (21 per cent; 95 per cent confidence limits: 10-37) with healing per primam developed recurrence of their pilonidal disease during the prospective follow-up period (median follow-up period was 60 months, range 36-84 months). Actuarial analysis of the data revealed a constant cure rate of 76 per cent (95 per cent confidence limits: 57-95) after 18 months.

Acute Disease↗