Microalgal Peloids for Cosmetic and Wellness Uses.

Peloids have been used for therapeutic purposes since time immemorial, mainly in the treatment of locomotor system pathologies and dermatology. Their effects are attributed to their components, i.e., to the properties and action of mineral waters, clays, and their biological fraction, which may be made up of microalgae, cyanobacteria, and other organisms present in water and clays. There are many studies on the therapeutic use of peloids made with microalgae/cyanobacteria, but very little research has been done on dermocosmetic applications. Such research demonstrates their potential as soothing, regenerating, antioxidant, anti-inflammatory, and antimicrobial agents. In this work, a method for the manufacture of a dermocosmetic peloid is presented based on the experience of the authors and existing publications, with indications for its characterization and study of its efficacy.

Treatment with LA-419 prevents monocrotaline-induced pulmonary hypertension and lung injury in the rat.

We evaluated the therapeutic potential of LA-419, a hybrid organic nitrate that donates nitric oxide and thiol groups, to improve pulmonary arterial hypertension in an experimental model induced by monocrotaline in the rat. Treatment with LA-419 from the first day after monocrotaline administration prevented the increase in pulmonary pressure as well as the increases in ventricle/body weight and pulmonary artery wall thickness. Administration of LA-419 after establishment of hypertensive status also resulted in an improvement of these parameters. Both preventive and therapeutic treatments reduced mortality. The antioxidant effect of LA-419 was comparable to that achieved with a-tocopherol. Pulmonary remodeling accomplished by LA-419 could be attributed to a balanced antioxidant effect associated with its nitric oxide/SH donor capability. Thus, LA-419 might represent a new therapeutic approach in severe pulmonary hypertension in humans.

Selective inhibition of phosphodiesterase-4 ameliorates chronic colitis and prevents intestinal fibrosis.

The phosphodiesterase-4 (PDE4) inhibitors may be an important target in the treatment of several inflammatory conditions. The anti-inflammatory effect of PDE4 inhibitors bears similarities with that of steroids, without interfering with the hypophysary-adrenal-axis. We compared the effect of rolipram, a selective PDE4 inhibitor, with steroids on the clinical course of experimental colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Three groups of rats (n = 20) received TNBS. One group received methylprednisolone from day 7, another group received rolipram from the same day, and control group received no further treatment. On days 14 and 21 after TNBS instillation, sets of 10 rats underwent colonic dialysis to measure eicosanoid release. Colonic lesions were blindly scored, and colons were homogenized for quantification of myeloperoxidase (MPO) activity and collagen content. Concentration of tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta1 (TGF-beta1) in colonic tissue was also measured. Both treatments reduced significantly the eicosanoid release and MPO activity. On day 14, both rolipram and methylprednisolone significantly reduced TNF-alpha content, but TGF-beta1 was only inhibited by rolipram. On day 21, lesion scores and collagen content were significantly reduced only in rolipram-treated group. In conclusion, PDE4 inhibition by rolipram markedly ameliorates the course of chronic colitis and it is superior to methylprednisolone in preventing late collagen deposition.

New 3-[4-(3-substituted phenyl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propanol derivatives with dual action at 5-HT1A serotonin receptors and serotonin transporter as a new class of antidepressants.

In this paper a series of new 3-[4-(3-substituted phenyl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propanol derivatives is presented as a new class of antidepressant drugs with dual activity at 5-HT1A serotonin receptors and serotonin transporter. The 5-HT1A receptor and 5-HT transporter binding affinities of hydroxylic compounds 4 a-e have been determined. The new compounds present nanomolar affinity for both activities, and 1-(benzo[b]thiophen-3-yl)-3-[4-(3-methoxyphenyl)piperazin-1-yl]propan-1-ol (4d) shows values (nM) of Ki = 86 for 5-HT1A receptors and Ki = 76 for the serotonin transporter, respectively.

New 1-aryl-3-(4-arylpiperazin-1-yl)propane derivatives, with dual action at 5-HT1A serotonin receptors and serotonin transporter, as a new class of antidepressants.

In a search toward new and efficient antidepressants, 1-aryl-3-(4-arylpiperazin-1-yl)propane derivatives were designed, synthesized, and evaluated for 5-HT reuptake inhibition and 5-HT1A receptor antagonism. This dual pharmacological profile should lead, in principle, to a rapid and pronounced enhancement in serotoninergic neurotransmission and consequently to a more efficacious treatment of depression. The design was based on coupling structural moieties related to inhibition of serotonin reuptake, such as gamma-phenoxypropylamines, to arylpiperazines, typical 5-HT1A ligands. In binding studies, several compounds showed affinity at the 5-HT transporter and 5-HT1A receptors. Antidepressant-like activity was initially assayed in the forced swimming test with those compounds with Ki < 200 nM in both binding studies. Functional characterization was performed by measuring the intrinsic effect on rectal temperature in mice and also the antagonism to 8-OH-DPAT-induced hypothermia. The most efficacious compounds (12f, 23gE, 28a, and 28b) were further explored for their ability to antagonize 8-OH-DPAT-induced inhibition of forskolin-stimulated cAMP formation in a cell line expressing the 5-HT1A receptor. Furthermore, the antidepressant-like properties of 12f, 28a, and 28b, which exhibited 5-HT1A receptor antagonistic property in the latter study, were also evaluated in the learned helplessness test in rats. Among these three compounds, 28b (1-benzo[b]thiophene-3-yl)-3-[4-(2-methoxyphenyl)-1-ylpropan-1-ol) showed the higher affinity at both the 5-HT transporter and 5-HT1A receptors (Ki = 20 nM in both cases) and was also active in the other pharmacological tests. Such a pharmacological profile could lead to a new class of antidepressants with a dual mechanism of action and a faster onset of action.

New 3-[4-(aryl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propane derivatives with dual action at 5-HT1A serotonin receptors and serotonin transporter as a new class of antidepressants.

A series of new 3-[4-(aryl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propane derivatives were synthesized in an attempt to find a new class of antidepressant drugs with dual activity at 5-HT1A serotonin receptors and serotonin transporter. Title compounds were evaluated for in vitro activity on 5-HT1A receptor and 5-HT transporter. They show high nanomolar affinity for both activities, and in particular, compounds 1-(5-chlorobenzo[b]thiophen-3-yl)-3-[4-(2-methoxyphenyl)piperazin-1-yl]propan-1-ol (7) and 1-(5-fluorobenzo[b]thiophen-3-yl)-3-[4-(2-methoxyphenyl)piperazin-1-yl]propan-1-ol (8) show values (nM) of K(i)=30 and 2.3 for 5-HT1A receptors and K(i)=30 and 12 for serotonin transporters, respectively. In GTPgammaS binding assays, compound 8 revealed antagonist properties to 5-HT1A receptors. Such a pharmacological profile could lead to potent antidepressant agents with new dual mechanism of action.

Epidermal growth factor increases surface hydrophobicity and resistance to acid in the rat duodenum.

Epidermal growth factor (EGF) is produced in Brunner's glands and plays a role in healing and repair of duodenal ulcers. We examined the participation of zwitterionic phospholipids of mucus in the effects of EGF. Under anesthesia, groups of rats received an intraduodenal bolus of either saline or EGF. Some rats received subcutaneous indomethacin followed by EGF or EGF followed by a detergent (5% Brij 35, a nonionic detergent that solubilizes luminal phospholipids). Thirty minutes after treatment, mucosal surface hydrophobicity and phospholipid concentration in the mucus layer were measured. Matched groups of rats were challenged with 0.5 M HCl, instilled intraduodenally 30 min after treatment, and mucosal damage was assessed 1 h after acid challenge. Exogenous EGF significantly increased surface hydrophobicity and phosphatidylcholine concentration in the mucus layer. EGF treatment also reduced mucosal damage induced by acid. However, indomethacin pretreatment or detergent administration after EGF abolished both protection against acid and changes in the mucus layer. These data suggest that EGF increases duodenal resistance to luminal acid via stimulation of mucosal zwitterionic phospholipids.

Characterisation of immune mediator release during the immediate response to segmental mucosal challenge in the jejunum of patients with food allergy.

BACKGROUND: Food allergy is a common complaint among patients with a broad spectrum of abdominal and extra-abdominal symptoms that must be distinguished from other more common non-immunological food intolerances. AIMS: To investigate whether human intestinal hypersensitivity reactions are associated with detectable release of inflammatory mediators from activated cells, which may serve as a biological marker of true allergic reactions. PATIENTS/METHODS: In eight patients with food allergy and seven healthy volunteers, a closed-segment perfusion technique was used to investigate the effects of jejunal food challenge on luminal release of tryptase, histamine, prostaglandin D(2), eosinophil cationic protein, peroxidase activity, and water flux. RESULTS: Intraluminal administration of food antigens induced a rapid increase in intestinal release of tryptase, histamine, prostaglandin D(2), and peroxidase activity (p<0.05 v basal period) but not eosinophil cationic protein. The increased release of these mediators was associated with a notable water secretory response. CONCLUSIONS: These results suggest that human intestinal hypersensitivity reactions are characterised by prompt activation of mast cells and other immune cells, with notable and immediate secretion of water and inflammatory mediators into the intestinal lumen. Analysis of the profile of markers released into the jejunum after food provocation may be useful for the objective diagnosis of food allergy.

Mucosal mast cells are involved in CCK disruption of MMC in the rat intestine.

Our aim was to determine if mucosal mast cells could be activated by endogenous CCK and, as a consequence, mediate CCK actions in the small intestine. Rats were prepared for electromyography to record electrical activity in the small intestine. In another group of animals, the duodenum was perfused to measure rat mast cell protease II (RMCP II) as indicative of mast cell degranulation. Endogenous CCK release was induced by administration of soybean trypsin inhibitor (SBTI) in conscious rats or by intraduodenal perfusion of ovalbumin hydrolysate (OVH) in anesthetized rats. CCK concentration was measured by bioassay on pancreatic acini. SBTI in control rats disrupted migrating motor complexes (MMC) for >40 min. In rats treated with the mast cell stabilizer ketotifen, SBTI did not induce any change in the MMC pattern. RMCP II concentration in the duodenal perfusate significantly increased after OVH. Perfusate from ketotifen-treated animals did not show any significant increase in RMCP II values during OVH perfusion, although CCK plasma concentration was not different from the control group. Furthermore, infusion of the CCK-B receptor antagonist L-365,260 significantly blocked the increase of RMCP II concentration after OVH. Our results indicate that mucosal mast cells are degranulated by endogenous CCK release through stimulation of CCK-B receptors. Therefore mucosal mast cells participate in CCK intestinal actions.

Release of mast cell mediators into the jejunum by cold pain stress in humans.

BACKGROUND & AIMS: The central nervous system regulates gut functions via complex interactions between the enteric nervous and immune systems. The aim of this study was to investigate whether mast cell mediators are released into the human jejunal lumen during stress. METHODS: A closed-segment perfusion technique was used to investigate jejunal release of tryptase, histamine, prostaglandin D2, and water flux in response to the cold pressor test in 8 healthy subjects and 9 patients with food allergy. In 6 food-allergic patients, jejunal biochemical responses to cold pain stress were compared with those induced by food intraluminal challenge. RESULTS: Cold pain stress elevated heart rate and blood pressure and increased luminal release of mast cell mediators and jejunal water secretion in both groups. Stress-induced release of tryptase and histamine, but not of prostaglandin D2 and water flux, was greater in food-allergic patients than in healthy volunteers. In food-allergic patients, jejunal biochemical responses induced by cold pain stress were similar to those induced by antigen challenge. CONCLUSIONS: These results show the ability of the central nervous system to modulate intestinal mast cell activity and suggest that mast cells have a role in stress-related gut dysfunction.

Stimulation of transforming growth factor beta1 by enteric bacteria in the pathogenesis of rat intestinal fibrosis.

BACKGROUND & AIMS: Bacteria and their products stimulate inflammatory responses. Certain mediators, such as transforming growth factor beta1 (TGF-beta1), induce collagen synthesis. Excess collagen deposition results in bowel strictures. The aim of this study was to investigate the role of bacteria and TGF-beta1 in the pathogenesis of intestinal fibrosis. METHODS: In rats with colitis, the effects of bowel decontamination with antibiotics on TGF-beta1, tumor necrosis factor alpha (TNF-alpha), and collagen content in colonic tissue were studied. In normal rats, bacteria of the predominant flora were inoculated into the colonic wall. The effect of neutralizing antibody to TGF-beta1 on tissue collagen deposition was studied. RESULTS: Rats with chronic colitis showed increased levels of TGF-beta1, TNF-alpha, and collagen in the tissue and a high rate of bowel strictures. Antibiotic treatment significantly prevented the increase in TGF-beta1 and collagen and the formation of strictures. Inoculation of bacterial suspensions into the colonic wall increased tissue TGF-beta1 and collagen content. Neutralizing antibody to TGF-beta1 prevented collagen deposition. Colonic wall inoculations with single anaerobic strains (Clostridium ramosum, Bacteroides fragilis, and Bacteroides uniformis), but not with aerobes, induced collagen deposition. CONCLUSIONS: Certain strains of the common flora stimulate TGF-beta1 and induce deposition of collagen in the colonic wall.

Deranged hydrophobic barrier of the rat gastroduodenal mucosa after parenteral nonsteroidal anti-inflammatory drugs.

BACKGROUND & AIMS: Parenteral administration of nonsteroidal anti-inflammatory drugs (NSAIDs) may cause gastrointestinal mucosal lesions. The aim of this study was to investigate whether parenteral NSAIDs alter surface hydrophobicity of the gastroduodenal mucosa. METHODS: Conscious rats received indomethacin or diclofenac subcutaneously at different doses (0.5-10 mg/kg). Surface hydrophobicity of gastric and duodenal mucosa was determined by contact angle measurement at various time points; mucosal prostaglandin synthesis and mucus phospholipid content were measured. Also, the effects of NSAIDs were studied in bile duct-ligated rats. RESULTS: A single 1-2-mg/kg dose significantly decreased hydrophobicity in the stomach and duodenum. The decrease was associated with a reduction in mucus phosphatidylcholine. In the duodenum, mucosal prostaglandin synthesis was restored 24 hours after NSAID dosing, but hydrophobicity was still decreased. There was no adaptation to long-term treatment. In bile duct-ligated rats, NSAIDs did not decrease gastric or duodenal hydrophobicity. Moreover, oral administration of bile from rats pretreated with parenteral NSAIDs significantly decreased mucosal hydrophobicity in untreated rats. CONCLUSIONS: Low-dose NSAIDs by parenteral route impair the physicochemical barrier against luminal acidity and render the mucosa susceptible to injury. Excretion of NSAIDs in bile seems to play a key role in this effect.

Effect of portal vein ligation and silymarin treatment on aspirin metabolism and disposition in rats.

The influence of portal hypertension on the metabolism and pharmacokinetics of aspirin was evaluated after the administration of a single oral dose of acetylsalicylic acid (20 mgkg(-1)) in portal-vein-ligated (PVL) rats. Experiments were also performed in control (sham-operated rats) and in rats that received an oral daily dose (150 mgkg(-1)) of silymarin from the tenth day after surgery for 7 d. Plasma concentration profiles of all groups exhibited monoexponential decay but with important changes in pharmacokinetic parameters. The aspirin elimination constant (k) for PVL rats was lower than for control rats, whereas the plasma half-life and area under the curve were greater than those in the control group. However, Cmax was comparable with that of the control rats. Urinary excretion of the metabolites (salicylic acid and glucuronides) was significantly altered in PVL rats: the urinary glucuronides were reduced and urinary salicylic acid was increased. The activities of plasma and liver esterases were increased significantly in PVL rats, while the activity of p-nitroanisole-O-demethylase was not affected. Depletion of cytochrome P 450 was also noted in the same group of rats. Silymarin markedly reversed the alterations found in the PVL group.

Regulation of intestinal mast cells and luminal protein release by cerebral thyrotropin-releasing hormone in rats.

BACKGROUND & AIMS: Intestinal mast cell activity is modulated by the central nervous system, but the mechanisms are not well established. The aim of this study was to investigate whether cerebral thyrotropin-releasing hormone (TRH) activates intestinal mast cells and to elucidate the mechanisms involved, specifically, the contribution of mast cells to vagally stimulated luminal protein release. METHODS: In anesthetized rats, mast cell activation was assessed by measuring the release of the specific mucosal rat mast cell protease II (RMCP II) and prostaglandin (PG) D2 into the intestinal lumen. Luminal protein release was measured as an index of epithelial permeability to macromolecules. RESULTS: Intracisternal injection of the TRH analogue RX 77368 (30 ng) induced a transient increase in intestinal release of RMCP II and PGD2 that was abolished by dox-antrazole. RX 77368-stimulated RMCP II release was also abolished by vagotomy and reduced by atropine by 65%. However, both systemic capsaicin and indo-methacin enhanced RMCP II release. RX 77368-stimulated luminal protein release was abolished by vagotomy and reduced by doxantrazole. CONCLUSIONS: Central vagal activation by TRH stimulates intestinal mast cell secretion, in part via peripheral muscarinic receptors, and is modulated by PGs and capsaicin-sensitive afferent innervation. Intestinal mast cell activation contributes to the TRH analogue-stimulated luminal protein release.

Effect of colchicine and trimethylcolchicinic acid on CCl4-induced cirrhosis in the rat.

Colchicine is one of the most promising drugs for the treatment of cirrhosis. However, due to its toxicity, other drugs are being evaluated and colchicine-like molecules may be good alternatives. The aim of this work was to compare the beneficial effects of colchicine and trimethylcolchicinic acid (a colchicinoid less toxic than colchicine) on CCl4-cirrhosis. The drugs were administered either through CCl4 administration (8 weeks) or after CCl4 intoxication for 4 weeks at a dose of 10 micrograms/rat/day, orally. Liver plasma membranes were isolated for high affinity Ca(2+)-ATPase, gamma-glutamyl transpeptidase and alkaline phosphatase activities. The activities of gamma-glutamyl transpeptidase and alkaline phosphatase were also measured in serum. Liver glycogen content and a marker for lipid peroxidation were determined in liver samples. We found that both compounds preserved and significantly reversed high affinity Ca(2+)-ATPase, gamma-glutamyl transpeptidase and alkaline phosphatase plasma membrane and serum enzyme activities as well as the hepatic glycogen content.

Coronary denervation attenuates coronary constriction induced by muscarinic receptor stimulation in pigs.

OBJECTIVES: We tested the hypothesis that coronary denervation attenuates the reactivity of the coronary vessel to cholinergic stimulation. METHODS: Heart rate, left ventricular (LV) pressure, LV dP/dt, coronary blood flow at the left anterior descending (LAD) coronary artery, and epicardial ECG mapping were measured before and after topical application of 1% methacholine to the LAD in 10 pigs anesthetized with alpha-chloralose (100 mg/kg, i.v.); these were compared with 10 other pigs submitted 2 weeks previously to a denervation of the LAD with phenol. Coronary denervation was confirmed in all cases by adrenergic histofluorescence and by acetyl-cholinesterase staining. Isolated LAD rings from 10 additional pigs (5 controls and 5 treated with phenol) were stimulated with endothelin-1 to verify whether phenol affected coronary reactivity to noncholinergic stimulation. RESULTS: Methacholine induced a fall in coronary blood flow (10.3 +/- 5.3 ml/min vs 4.8 +/- 6.2 ml/min, ANOVA: P < 0.001), a drop in systolic LV pressure (113 +/- 19 mmHg vs 93 +/- 19 mmHg, P < 0.001) and LV dP/dt (1608 +/- 363 mmHg/s vs 1203 +/- 302 mmHg/s, P = 0.02) and elevation of the ST segment (1.4 +/- 0.9 vs 11.1 +/- 4.7 mV, P < 0.001) in controls. These changes were not preceded by heart rate variations and were inhibited by atropine. As compared to controls, phenol-treated pigs showed a smaller decline in coronary blood flow (13.1 +/- 4.5 ml/min to 10.4 +/- 5.4 ml/min, P < 0.001), a lower drop in LV pressure (107 +/- 20 mmHg to 100 +/- 19.7 mmHg, P < 0.001) and lesser ST segment elevation (2.2 +/- 1.7 mV to 5.6 +/- 4.2 mV, P < 0.001). Isolated LAD rings contracted after exposure to endothelin-1 in both controls and phenol-treated pigs (3.5 +/- 0.7 g vs 2.4 +/- 1.0 g, P = 0.06). CONCLUSIONS: Coronary denervation attenuates coronary constriction induced selectively by direct muscarinic receptor stimulation in the in situ pig heart.

Bile acid induced colonic irritation stimulates intracolonic nitric oxide release in humans.

AIM: To measure the intracolonic release of nitric oxide end products (nitrates plus nitrites) and eicosanoids in response to intraluminal irritation with deoxycholic acid (DCA). PATIENTS: Seven patients with irritable bowel syndrome. METHODS: The left colon was perfused with a solution with or without 3 mM deoxycholic acid. Aspirates were assayed for eicosanoids by specific radioimmuno-assay, and for nitrates plus nitrites by the Griess reaction. To confirm that stimulated colonic mucosa can produce nitric oxide (NO), ancillary studies were performed in vitro using samples of normal mucosa obtained from five surgically resected colons. Samples were incubated for 30 minutes in Kreb's solution, 3 mM DCA or DCA with 1 mM L-nitro-arginine-methyl-ester (L-NAME) to inhibit the NO synthase. Finally, NO synthase activity was measured in five samples of human colonic mucosa. RESULTS: Intracolonic release of nitrates plus nitrites was basally undetectable in six of seven patients. Bile acid considerably increased the release of prostaglandin E2 and nitrates plus nitrites (p < 0.01). By contrast, no increase in thromboxane and leukotriene was seen. In vitro mucosal incubation with DCA increased the production of NO synthase products, which was blocked by L-NAME. Activity of Ca+2 independent NO synthase was detectable in four of five samples of human colonic mucosa. CONCLUSION: The human colonic mucosa responds to bile acid induced irritation by a surge in NO generation via NO synthase.

Acute and chronic cyclooxygenase blockage in portal-hypertensive rats: influence in nitric oxide biosynthesis.

BACKGROUND & AIMS: Prostacyclin and nitric oxide have been involved in the hyperkinetic syndrome in portal hypertension. The aim of this study was to investigate the relative contribution and possible interaction between prostacyclin and NO in this circulatory abnormality. METHODS: Portal vein-ligated and sham-operated rats received indomethacin and vehicle either on a short-term (5 mg/kg subcutaneously) or long-term basis (5 mk.kg-1.day-1, continuous 7-day infusion with an osmotic minipump). Measurements of arterial pressure and superior mesenteric arterial flow (mL.min-1.kg-1, ultrasonic flow probe) were then performed before and after NG-nitro-L-arginine methyl ester (L-NAME) injection (13 mg/kg intravenously). RESULTS: Short-term or long-term indomethacin treatment had no effect in sham-operated rats but significantly decreased mesenteric arterial flow in portal-hypertensive rats. Mesenteric flow remained higher after long-term than after short-term indomethacin treatment (54.5 +/- 2 vs. 46.1 +/- 2; P = 0.01). This blunted response to long-term indomethacin treatment was associated with an enhanced response to L-NAME, shown by greater increments in arterial pressure (29% +/- 3%) and mesenteric arterial resistance (209 +/- 22%) in indomethacin-treated rats than in rats receiving vehicle (19% +/- 2% and 130% +/- 20%; P < 0.05). CONCLUSIONS: Both prostacyclin and NO contributed to splanchnic hyperemia in portal-hypertensive rats. There was an enhanced release of NO after long-term prostacyclin inhibition, suggesting that both vasodilatory systems interact, promoting splanchnic hyperemia in portal hypertension.

Role of prostaglandins and nitric oxide in gastrointestinal hyperemia of diabetic rats.

The aim of the study was to characterize the gastric and mesenteric vascular changes induced by diabetes and the implication of endothelial [nitric oxide (NO) and prostaglandins] and humoral (glucagon) factors in such changes. Diabetes was induced in rats by a single streptozotocin injection. Four weeks later, gastric mucosa, left gastric artery, and superior mesenteric artery blood flows were measured using hydrogen gas clearance and perivascular ultrasonic flowmeter techniques, respectively, in anesthetized and fasted diabetic and control rats. Blood pressure, hematocrit, blood volume, and blood viscosity were also measured. Left gastric (41 +/- 6 vs. 25 +/- 4 ml.min-1.100 g-1) and superior mesenteric artery blood flows (83 +/- 8 vs. 65 +/- 4 ml.min-1.100 g-1) were significantly higher in diabetic than in control rats. The increased blood flow in the left gastric artery was distributed to a hypertrophic mucosa in diabetic rats; therefore, the blood flow per 100 g tissue in the gastric mucosa was not significantly different in diabetic compared with control rats. Pretreatment with indomethacin reduced both increase gastric and mesenteric flows of the diabetic rats to the same levels as in control rats. NG-nitro-L-arginine methyl ester decreased gastric blood flow in a dose-dependent manner and to a similar extent in diabetic and control rats. In contrast, an increased sensitivity to the higher doses of the NO inhibitor was observed in the mesenteric vascular bed of diabetic rats. Glucagon reduction achieved by somatostatin infusion did not influence either gastric or mesenteric blood flow in diabetic rats. In summary, the present study revealed an increase in gastric and mesenteric arterial blood flows in streptozotocin-induced diabetic rats. The gastrointestinal hyperemia seems to be due, at least in part, to the increased demand of a hypertrophic mucosa and is mediated primarily by endogenous prostaglandins. Increased vascular sensitivity to NO may also contribute to the mesenteric vasodilation.

Polyunsaturated phosphatidylcholine prevents stricture formation in a rat model of colitis.

BACKGROUND & AIMS: Polyunsaturated phosphatidylcholine stimulates collagen breakdown in experimental models of liver cirrhosis. Bowel strictures are characterized by excess deposition of collagen in the intestinal wall. The aim of this study was to investigate the effect of polyunsaturated phosphatidylcholine in the prevention of bowel strictures. METHODS: Colitis was induced by trinitrobenzenesulfonic acid. On day 21, the presence of strictures was assessed in control rats, rats with colitis, and phosphatidylcholine-fed (100 mg/day) rats with colitis. Furthermore, serum transforming growth factor beta1, collagen deposition, and collagenase activity in colonic tissue were measured in all groups. RESULTS: None of the control rats but 12 of 16 rats with colitis developed colonic strictures. In contrast, only 2 of 15 phosphatidylcholine-fed rats with colitis showed strictures. Collagen content was much higher in rats with colitis than in phosphatidylcholine-fed rats with colitis and control rats. Phosphatidylcholine-fed rats showed significantly higher collagenase activity in colonic tissue than rats with colitis and control rats. In an ancillary study, free linoleic acid-fed rats showed no differences when compared with rats with colitis. Stimulation of transforming growth factor beta1 was similar in all rats with colitis. CONCLUSIONS: Oral supplementation with polyunsaturated phosphatidylcholine prevents the accumulation of collagen in inflamed intestinal tissue and the formation of strictures. This effect is associated with an enhanced collagen catabolism.