bluuebunny/crossref_metadata_2025_split huggingface dataset:
VASOPRESSIN COMPENSATES FOR ACUTE LOSS OF SYMPATHETIC PRESSOR TONE IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Jablonskis Lina T. , Howe Peter R. C. 
Published: June 2007

SUMMARY1. The aim of this study was to examine the pressor response of vasopressin (AVP) to an acute fall in blood pressure induced by ganglion blockade.2. Aortic catheters were implanted in spontaneously hypertensive rats (SHR), stroke‐prone SHR (SHRSP), normotensive Wistar‐Kyoto (WKY), black‐hooded Wistar (BHW) and Sprague‐Dawley (SD) rats, aged 5–7 weeks and 7–9 months, for direct measurement of mean arterial pressure (MAP) under conscious, resting conditions. The ganglion blocking agent pentolinium was administered intra‐arterially, followed by an AVP receptor antagonist specific for the pressor effect of AVP. The basal level of MAP attained with each drug was recorded.3. In the adult SHR and SHRSP with established hypertension, acute ganglion blockade caused MAP to fall to a similar extent as in WKY, suggesting that the level of sympathetic pressor tone was similar in all three strains. Administration of the AVP antagonist alone did not affect resting MAP. During ganglion blockade, however, it caused a further reduction of MAP in WKY, SHR and SHRSP, the magnitude of which was greater in the hypertensive strains. After both drugs, the total fall in MAP and the residual MAP were significantly greater in the hypertensive rats.4. In young rats, AVP had little effect on MAP, even during ganglion blockade. The residual level of MAP after both drugs was greater in the hypertensive strains.5. The extent to which AVP can compensate for an acute fall in MAP increases with age and the development of hypertension. This tends to mask the loss of sympathetic mediated pressor tone after ganglion blockade. By preventing this compensation we have shown that the sympathetically mediated component of blood pressure is elevated in SHRSP with established hypertension.
AGEING AND BLOOD PRESSURE REGULATION: DOSE‐RESPONSE RELATIONSHIPS FOR ANGIOTENSIN, BLOOD PRESSURE, ATRIAL NATRIURETIC PEPTIDE AND ALDOSTERONE IN NORMAL SUBJECTS OF VARYING AGES
Authors: Finn Wendy L. , Tunny Terry J. , Klemm Shelley A. , Ryan Susan J. , Gordon Richard D. 
Published: June 2007

SUMMARY1. Infusion of increasing doses of angiotensin II (AII) in normal subjects sequentially increased blood pressure, aldosterone and atrial natriuretic peptide (ANP) levels.2. The slope of ANP response to AII was positively correlated with basal ANP and with the slope of blood pressure response to AII (pressor slope) but not with age.3. This is consistent with the response of ANP to AII being mediated partly by the rise in blood pressure, independent of ageing.4. As expected in a selected normotensive population, there was no correlation between basal blood pressure and age, but pressor slope was positively correlated with age.5. Thus, dose‐response relationships may be an index of age‐induced alterations in pressure regulatory mechanisms.
EFFECTS OF DIABETES ON DISPOSITION AND HEPATIC HANDLING OF CEFMETAZOLE IN RATS
Authors: Barrientos C. , González P. , Tuñón M. J. , Culebras J. M. , González‐Gallego J. 
Published: June 2007

SUMMARY1. The effects of streptozotocin‐induced diabetes on disposition and hepatic handling of cefmetazole, a broad‐spectrum cephalosporin, were investigated in rats.2. Male Wistar rats were pretreated with streptozotocin (60 mg/kg, i.p.) to induce uncontrolled diabetes. Fourteen days later bile flow was significantly reduced (12%) and bile acid secretion was significantly enhanced (87%) when compared with control animals.3. Following intravenous injection of cefmetazole at a dose of 200 μmol/kg, maximal and cumulative biliary excretion of the antibiotic were significantly impaired in streptozotocin‐treated animals (27 and 22%, respectively).4. Cefmetazole excretion into bile was accompanied by marked choleresis. The magnitude of bile flow increase was larger in control animals.5. Total systemic clearance of the antibiotic was reduced (36%) and mean half‐life for the fast and slow phases of disposition increased (136 and 48%, respectively) in diabetic rats.6. These changes were probably due to the diabetic condition of the animals because insulin treatment resulted in almost complete cofrection.
DIFFERENT RESPONSES TO ACETYLCHOLINE IN THE PRESENCE OF NITRIC OXIDE INHIBITOR IN RAT AORTAE AND MESENTERIC ARTERIES
Authors: Wu Chin‐Chen , Chen Shiu‐Jen , Yen Mao‐Hsiung 
Published: June 2007

SUMMARY1. This study compared the relaxation induced by acetylcholine (ACh) in aortic and mesenteric arterial rings from Sprague‐Dawley (SD) rats in the presence and absence of inhibitors of the known endothelium‐derived relaxing factors.2. ACh‐induced relaxations were completely blocked by methylene blue and N”‐nitro‐L‐arginine (LNNA) in aortae, whereas these were only partially attenuated by methylene blue and LNNA in mesenteric arteries.3. This methylene blue‐resistant relaxation of ACh was partly attenuated by potassium channel blockers (tetraethylammonium and barium) but not affected by LNNA, indomethacin and calcium‐free solution.4. These results suggest that there may be another endothelial relaxing factor which is not nitric oxide (NO), prostanoids or endothelium‐derived hyperpolarizing factor (EDHF) in mesenteric arteries but not in aortae. This unknown factor seems to be extracellular calcium ([Ca2+]o)‐independent.
DO ANGIOTENSIN CONVERTING ENZYME INHIBITORS LIMIT MYOCARDIAL INFARCT SIZE?
Authors: Miki Takayuki , Miura Tetsuji , Shimamoto Kazuaki , Urabe Kazuyuki , Sakamoto Jun , Iimura Osamu 
Published: June 2007

SUMMARY1. Effects of captopril, ramiprilat and Hoe 140, a specific bradykinin receptor antagonist, on infarct size were assessed in a rabbit model of myocardial infarction.2. Rabbits were untreated or pretreated with 0.5 mg/kg of captopril, 0.05 mg/kg of ramiprilat or 20 nmol/kg of Hoe 140 before 30 min coronary artery occlusion and 72 h reperfusion.3. Captopril and ramiprilat treatment reduced systemic blood pressure by about 10 mmHg without alteration of heart rate, and the dose of Hoe 140 almost completely blocked hypotensive response to intravenous injection of bradykinin (100 ng/kg).4. Infarct size expressed as percentage of area at risk was 44.5 ± 3.3% in the control group, 41.9 ± 1.6% in the captopril group, 51.8 ± 2.7% in the ramiprilat group and 46.7 ± 2.2% in the Hoe 140 group. All percentages were not significantly different.5. These data suggest that angiotensin converting enzymes (ACE), with or without sulfhydryl groups do not limit myocardial infarct size and that endogenous bradykinin in ischaemic myocardium does not play a major protective role against ischaemic myocardial necrosis.
PLASMA FROM NORMAL PREGNANT WOMEN ALTERS THE REACTIVITY OF RABBIT AORTIC SMOOTH MUSCLE WITH FUNCTIONAL ENDOTHELIUM
Authors: Ezimokhai M. , Aloamaka C. P. , Cherian T. , Agarwal M. , Morrison J. 
Published: June 2007

SUMMARY1. The effects of normal human pregnant plasma on the reactivity of rabbit aortic rings with documented endothelium have been studied. The rings were incubated in plasma from either normal pregnant or non‐pregnant women and the effects of incubation on their responses to noradrenaline (NA), calcium chloride stimulation and potassium chloride‐induced relaxation were examined.2. There was no significant difference in the responses to NA in rings incubated in plasma from either pregnant or non‐pregnant women.3. The responses of the rings, incubated in both types of plasma, to calcium chloride stimulation through receptor‐operated channels were similar, but rings incubated in plasma from pregnant women demonstrated decreased sensitivity and contractility to calcium chloride stimulation through voltage operated channels.4. Potassium chloride‐induced relaxation was significantly enhanced in rings incubated in plasma from normal pregnant women. The pattern of the responses was unaltered by either de‐endothelialization or pretreatment of the rings with indomethacin.5. The effects of plasma from pregnant women are similar to what has been reported as characteristic of vascular smooth muscle in normal pregnancy.
EFFECTS OF PEPTIDE HISTIDINE ISOLEUCINE ON PANCREATIC EXOCRINE SECRETION IN ANAESTHETIZED DOGS
Authors: Iwatsuki K. , Ren L.‐M. , Chiba S. 
Published: June 2007

SUMMARY1. The effects of peptide histidine isoleucine (PHI) on pancreatic exocrine secretion were investigated in preparations of the isolated and blood‐perfused dog pancreas as compared with those of vasoactive intestinal peptide (VIP), secretin and glucagon.2. Each peptide tested was injected intra‐arterially (i.a.) as a single bolus. Graded doses of PHI (3–300 nmol/kg), VIP (1–100 nmol/kg) and secretin (0.01–0.3 nmol/kg) caused dose‐dependent increases in the secretion of pancreatic juice and bicarbonate outputs, but had little effect on the protein outputs. Glucagon (0.1–10 μmol/kg) produced a bell‐shaped dose—response curve for the secretory rate, bicarbonate and protein outputs.3. The secretory activity of 30 nmol/ kg of PHI corresponded roughly to that of 80 pmol/ kg of secretin, 9 nmol/kg of VIP and 0.6 μmol/kg of glucagon, respectively. Thus, based on administered dose, PHI was about 375 × less potent than secretin, 3 × less potent than VIP and 20 × more potent than glucagon.4. The PHI‐ and VIP‐stimulated secretions were inhibited by a VIP antagonist, but not by a glucagon antagonist, SCH23390 (a dopamine D‐1 antagonist), L‐364718 (a cholecystokinin antagonist) or atropine.5. Each peptide increased cyclic AMP concentration, but not cyclic GMP concentration, concomitant with the increase in pancreatic secretion.6. From these results, it is concluded that PHI produces an increase in pancreatic secretion by acting on VIP‐preferring receptors on the exocrine pancreatic gland of the dogs. This may be mediated at least in part through the increase of intracellular cyclic AMP concentrations.
ANALYSIS OF SECRETION AND EXPRESSION OF PLATELET‐DERIVED GROWTH FACTOR IN CULTURED ENDOTHELIAL CELLS FROM STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Iihara Koji , Sasahara Masakiyo , Saeki Yukikazu , Hashimoto Nobuo , Kikuchi Haruhiko , Hazama Fumitada 
Published: June 2007

SUMMARY1. We characterized the endothelial cell‐derived growth factors of SHRSP and Wistar Kyoto rats (WKY), respectively and found that platelet‐derived growth factor (PDGF)‐B chain related growth factor constituted a major portion of the mitogenic activity of the conditioned media of endothelial cells from both animals. There were no remarkable qualitative differences between the endothelial cell‐derived growth factors of SHRSP and WKY.2. Northern analysis revealed that the expression of PDGF‐B chain was 2–4‐fold enhanced in cultured aortic endothelial cells of SHRSP. This enhanced expression of PDGF‐B chain, which may be induced under chronic hypertensive conditions, is suggested to contribute to the increase in endothelial cell‐derived growth factors reported in this animal.
EFFECT OF ARGININE VASOPRESSIN AND PARATHYROID HORMONE‐RELATED PROTEIN ON RENAL FUNCTION IN THE OVINE FOETUS
Authors: Horne Rosemary S. C. , MacIsaac Richard J. , Moritz Karen M. , Tangalakis Kathy , Wintour E. Marelyn 
Published: June 2007

SUMMARY1. The effects of intravenous infusions of arginine vasopressin (AVP), parathyroid hormone‐related protein (PTHrP) and AVP + PTHrP on renal function in intact ovine foetuses at 100–125 days of gestation were examined.2. A low dose of AVP (5.5 ± 0.9 pmol/h) increased plasma AVP concentrations from 0.6 pmol/L to 2.1 ± 0.4 pmol/L (mean ± s.e.m; n= 8). This dose caused a significant reduction in free water clearance (CH2O; P<0.001), without any significant change in fetal arterial blood pressure, glomerular filtration rate (GFR), or the urinary excretion rates of sodium, calcium or 3', 5'‐cyclic adenosine monophosphate (CAMP).3. Infusions of PTHrP (1 nmol/h), with or without 1 nmol bolus dose, significantly increased (P<0.05) urine osmolality (Uosm), but did not synergize with AVP in reducing CH2O.4. It is concluded that AVP and PTHrP do not act synergistically on the kidney of the intact ovine foetus.
EFFECT OF XANTHINE DERIVATIVES ON CHEMOTACTIC POLYPEPTIDE‐INDUCED SUPEROXIDE AND ENZYME RELEASE FROM HUMAN POLYMORPHONUCLEAR LEUCOCYTES
Authors: Hirano Tsunekazu , Ando Morihide , Suzuki Kenji , Furui Hidehiko , Miyamoto Kenichi , Takagi Kenzo 
Published: June 2007

SUMMARY1. We investigated the effects of new xanthine derivatives, 1‐methyl‐3‐propyl xanthine (MPX) and 1,3‐dipropyl xanthine (DPX), and several other xanthine derivatives on N‐formyl‐methionyl‐leucyl‐phenylalanine‐induced superoxide and lysozyme release from human polymorphonuclear leucocytes (PMN).2. MPX and DPX at low concentrations (10−8‐10−9 mol/L) inhibited superoxide release from PMN by a maximum of 31.2 ± 10.6% and 49.8 ± 10.4% (mean ± s.d.), respectively, and 10−3 mol/L concentrations completely inhibited the release reactions (4.8 ± 1.2 and 7.6 ± 2.5% of control level). At 10−5 mol/ L, however, the inhibition did not occur (99.9 ± 7.3 and 110.2 ± 15.8% of control level). When PMN was pre‐incubated with adenosine deaminase (ADA, 0.1 U/mL), superoxide release from PMN was inhibited in a dose‐dependent manner by MPX and DPX and the interruption of the inhibition at 10−5 mol/L was not observed.3. Lysozyme release from PMN was inhibited by MPX at low concentrations (10−7‐10−6 mol/L) and high concentrations (10−3 mol/L). However 10−4 mol/L of MPX facilitated the release (23.7 ± 27.0%). When pretreated with ADA (0.1 U/mL), MPX suppressed lysozyme release in a dose‐dependent manner and the facilitation of the release at 10−4 mol/L was not observed.4. When comparing effects of some other xanthine derivatives on superoxide release, the interruption of the inhibition of superoxide release at 10−5 mol/L was commonly observed among xanthine derivatives with adenosine A2 antagonism.5. The results suggest that adenosine A2 antagonism of xanthine derivatives may interfere with their anti‐inflammatory effects at therapeutic concentrations (10−5‐10−4 mol/L).
EFFECT OF NICORANDIL ON POST‐ISCHAEMIC CONTRACTILE DYSFUNCTION IN THE HEART: ROLES OF ITS ATP‐SENSITIVE K’ CHANNEL OPENING PROPERTY AND NITRATE PROPERTY
Authors: Iwamoto Toshihiro , Miura Tetsuji , Urabe Kazuyuki , Itoya Masao , Shimamoto Kazuaki , Iimura Osamu 
Published: June 2007

SUMMARY1. This study aimed to characterize the effect of nicorandil (NC) on myocardial stunning and the role of ATP‐sensitive K+ (Katp) channel opening property in its cardioprotective action.2. In open‐chest anaesthetized rabbits, myocardial stunning was induced by 10 min of coronary occlusion followed by 30 min of reperfusion. As an index of regional contractile function, systolic thickening fraction (TF) was measured by an epicardial Doppler sensor. The doses of NC (10 μg/kg per min) and nitroglycerin (TNG) (1 μg/kg per min) were selected not to lower the systemic blood pressure significantly.3. In the untreated controls, TF at 30 min after reperfusion was 46.4 ± 2.9% of the baseline value, indicating myocardial stunning. Both NC and TNG significantly improved post‐ischaemic recovery of TF when administered during the pre‐ischaemic and post‐ischaemic periods (TF = 68.2 ± 6.4%, 64.7 ± 2.3%, respectively). However, when their infusion was restricted to a pre‐ischaemic 10 min period, TF recovery was improved by NC, but not by TNG (63.4 ± 7.9%, 40.9 ± 6.2%, respectively).4. Pretreatment with glibenclamide (GL; 0.3 mg/kg) did not influence the recovery of TF after the 10 rnin ischaemia (TF = 52.4 ± 3.9% at 30 min after reperfusion). However, after the GL injection, a cardioprotective effect from nicorandil pretreatment was not detected (TF = 51.3 ± 1.7%).5. These results suggest that nicorandil protects the myocardium against stunning by opening the Katp channel when it is given before ischaemia, and that the nitrate property of nicorandil may also play a role during the reperfusion period in attenuation of post‐ischaemic contractile dysfunction.
PLASMA RENIN ACTIVITY DURING HYPOTENSIVE RESPONSES TO ELECTRICAL STIMULATION OF CAROTID SINUS NERVES IN CONSCIOUS DOGS
Authors: Peters Tim K. , Kaczmarczyk Gabriele 
Published: June 2007

SUMMARY1. The interaction of electrical stimulation of the carotid sinus nerves (carotid sinus nerve stimulation, CSNS) with mechanisms of renin release was studied in conscious and unrestrained resting beagle dogs receiving a standardized diet (sodium intake, 4.5 mmol/kg bodyweight (bw); water intake, 91 mL/kg bw).2. By CSNS, mean arterial blood pressure (MAP) was lowered for periods of 20 min to levels between 101 ± 4 and 56 ± 5 mmHg.3. In another group of conscious dogs, renal perfusion pressure (RPP) was lowered to 95 ± 4 mmHg for periods of 20 min by partial suprarenal aortic occlusion in order to assess the influence of a reduced RPP on plasma renin activity (PRA) without concomitant CSNS.4. During CSNS, PRA increased markedly (> 100%) only when MAP was reduced below 75 mmHg.5. With aortic constriction and an RPP of 95 mmHg, the increase in PRA was 955%, which is more than three‐fold higher than the increase in PRA during CSNS at MAP levels <65 mmHg (314%).6. The observed responses indirectly support the hypothesis that basal activity in efferent renal nerve discharge is present even at rest and can be inhibited by CSNS, and furthermore suggests that CSNS attenuated the pressure‐dependent renin release.
RENAL DENERVATION POTENTIATES THE NATRIURETIC AND DIURETIC EFFECTS OF ATRIAL NATRIURETIC PEPTIDE IN ANAESTHETIZED RABBITS
Authors: Christy I. J. , Denton K. M. , Anderson W. P. 
Published: June 2007

SUMMARY1. The role of the renal nerves in modulating the action of atrial natriuretic peptide (ANP) in the kidney was studied by comparing the responses to ANP in innervated and surgically denervated kidneys in anaesthetized rabbits.2. A low dose of ANP (0.05 μg/kg per min, i.v.) was used to minimize the confounding effects of systemic hypotension.3. The natriuretic and diuretic responses to ANP were significantly greater in denervated kidneys than in kidneys with intact innervation. Sodium excretion from denervated kidneys rose by 7.49 ± 3.11 μmol/min in response to ANP (‐55%, P<0.05) compared to 0.84 ± 0.59 μmol/min (‐28%, NS) in innervated kidneys. Urine flow increased markedly in denervated kidneys by 73.2 ± 29.9 μmol/min (‐60%, P<0.05) but not in innervated kidneys.4. Fractional sodium excretion increased significantly in denervated kidneys in response to ANP (median 2.3% to median 3.0%, P<0.05).5. Renal blood flow, glomerular filtration rate (GFR) and glomerular capillary pressure were unchanged in response to ANP in either denervated or innervated kidneys. Pre‐glomerular vascular resistance fell in denervated kidneys during ANP infusion.6. The natriuresis and diuresis observed in the denervated kidneys, due to an increased fractional excretion of sodium without increases in GFR or glomerular capillary pressure, is consistent with effects of ANP on tubular reabsorption of sodium.7. Thus, ANP produced a natriuresis and diuresis at a low dose in denervated but not in innervated kidneys. This indicates that reflex activation of renal nerves may antagonize the renal effects of ANP.
EFFECTS OF CALCIUM‐ AND ETa‐RECEPTOR ANTAGONISTS ON ENDOTHELIN‐INDUCED VASOCONSTRICTION AND LEVELS OF ENDOTHELIN IN THE HUMAN INTERNAL MAMMARY ARTERY
Authors: Liu James J. , Casley David , Wojta Johann , Gallicchio Marisa , Dauer Ray , Johnston Colin I. , Buxton Brian F. 
Published: June 2007

SUMMARY1. The effects of the ETA receptor antagonist BQ123 and dihydropyridine calcium antagonists on the vasoconstrictor effect of endothlin‐1 (ET‐1) were studied in human isolated internal mammary artery (IMA). The effect of the calcium antagonist, nisoldipine, on ET‐1 levels has also been examined in cultured IMA endothelial cells (IMAEC).2. The results showed that BQ123 and the calcium antagonists nisoldipine, isradipine, nitrendipine and nifedipine fully relaxed IMA precontracted with 3 nmol/L ET‐1 with the EC50 values of 7.18 ± 0.09 (‐log mol/L) for BQ123, and 7.68 ± 0.07, 7.02 ± 0.12, 6.96 ± 0.08 and 6.89 ± 0.09 for the calcium antagonists, respectively.3. Pretreatment of IMA with 10, 30, 100 and 300 nmol/L nisoldipine significantly depressed the maximal response (Max; 88.3 ± 5.1, 75.2 ± 4.9, 59.3 ± 5.6 and 56.2 ± 4.8% of maximal noradrenaline response versus 99.1 ± 13.2% in control, P<0.01) of IMA to ET‐1 without a significant change in the EC50 values.4. Pretreatment of IMA with 300 nmol/L BQ123 significantly increased both the EC50 (7.97 ± 0.09 vs 8.36 ± 0.08 in the control, P<0.05) and the Max (138.1 ± 10.2%vs the control, P< 0.01) of IMA to ET‐1.5. Incubation of IMAEC with nisoldipine for 7h resulted in a dose‐dependent (10−8–10−5 mol/L) reduction up to 93.1% in ET levels in the conditioned media.6. ET levels in the cell lysates were not detectable either in the absence or in the presence of nisoldipine, suggesting the reduction of ET levels in the media could be due to inhibition of ET synthesis.7. In conclusion, these studies demonstrate that: (i) both BQ123 and the calcium antagonists are potent relaxant agents of human IMA precontracted with ET‐1; (ii) BQ123 also increases the Max of IMA to ET‐1 and the mechanism is unknown; (iii) the calcium antagonist nisoldipine reduces ET levels in the cultured human IMAEC.
EFFECTS OF ANTI‐EMETICS ON WATER EXCRETION IN HUMANS
Authors: Phillips P. A. , Burrell L. M. , Risvanis J. , Stephenson J. , Johnston C. I. , Hutchins A‐M. 
Published: June 2007

SUMMARY1. The anti‐emetic drug metoclopramide has been shown to stimulate secretion of the antidiuretic hormone arginine vasopressin. Since metoclopramide is used to treat nausea, which is another potent stimulus to vasopressin secretion, the aim of this study was to determine whether metoclopramide might limit free water excretion and so cause hyponatraemia.2. Metoclopramide 20 mg (0.2–0.3 mg/kg), prochlorperazine 12.5 mg (0.1–0.2 mg/kg) and placebo were administered intravenously in a double blind randomized crossover way at 2 week intervals and the effects on urine flow rate, plasma osmolality, thirst ratings and plasma sodium and atrial natriuretic peptide concentrations determined in water‐loaded (10 mL/kg) healthy young men.3. There were no differential effects on any variable of either drug versus placebo.4. These results indicate that metoclopramide is unlikely to cause any significant water retention in a clinical setting or precipitate hyponatraemia.
DOES PHOSPHORYLATION AFFECT TRANSPORT OF INORGANIC PHOSPHATE?
Authors: Mary P. L. , Rao J. Prakasa 
Published: June 2007

SUMMARY1. This study investigated the effects of fructose and 2‐deoxyglucose on the uptake and release of phosphate from everted intestinal sacs of mice.2. Both the sugars significantly decreased the release of phosphate without affecting the uptake.3. Succinate and fumarate were able to partially reverse the inhibition of phosphate release exerted by fructose but not that exerted by 2‐deoxyglucose.4. Pre‐loading with mannoheptulose, a known inhibitor of hexokinase, improved the release of phosphate in the presence of either of these sugars.5. Adrenaline, known to inhibit phosphorylation of 2‐deoxyglucose, reduced the inhibition exerted by this sugar on phosphate release.6. These results indicate that the inhibition of phosphate release caused by these sugars may be due to the trapping of free phosphate during their metabolism in the gut wall.