Gastric Acid Secretion In Rats Research Articles

Investigating the L-Glu-NMDA receptor-H2S-NMDA receptor pathway that regulates gastric function in rats’ nucleus ambiguus

Investigating the L-Glu-NMDA receptor-H2S-NMDA receptor pathway that regulates gastric function in rats’ nucleus ambiguus

Design, synthesis and biological evaluation of novel 5-methyl-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives as potent potassium-competitive acid blockers

With the aim to discover a novel potent potassium-competitive acid blocker (P-CAB) agent, a series of 5-methyl-2,4,5,6-tetrahydropyrrolo[3,4–c]pyrazole derivatives were synthesized, and their H+/K+-ATPase inhibitory activities and inhibitory action on histamine-stimulated gastric acid secretion in rats were evaluated. Among the compounds synthesized, compound 3′-((3-(2-fluorophenyl)-5-methyl-5,6-dihydropyrrolo[3,4–c]pyrazol-2(4H)-yl)methyl)-[1,1′-biphenyl]-3-carboxamide not only exhibited potent H+/K+-ATPase inhibitory activity but olso showed potent inhibitory action in vivo on histamine-stimulated gastric acid secretion. In addition, the lead compound displayed favourable oral pharmacokinetic properties in rats, which was worthy of further study as a novel P-CAB agent.

Effects of Exogenous Hydrogen Sulfide in the Hypothalamic Paraventricular Nucleus on Gastric Function in Rats.

Background: Hydrogen sulfide (H2S) is a new type of gas neurotransmitter discovered in recent years. It plays an important role in various physiological activities. The hypothalamus paraventricular nucleus (PVN) is an important nucleus that regulates gastric function. This study aimed to clarify the role of H2S in the paraventricular nucleus of the hypothalamus on the gastric function of rats. Methods: An immunofluorescence histochemistry double-labelling technique was used to determine whether cystathionine-beta-synthase (CBS) and c-Fos neurons are involved in PVN stress. Through microinjection of different concentrations of NaHS, physiological saline (PS), D-2-Amino-5-phosphonovaleric acid (D-AP5), and pyrrolidine dithiocarbamate (PDTC), we observed gastric motility and gastric acid secretion. Results: c-Fos and CBS co-expressed the most positive neurons after 1 h of restraint and immersion, followed by 3 h, and the least was at 0 h. After injection of different concentrations of NaHS into the PVN, gastric motility and gastric acid secretion in rats were significantly inhibited and promoted, respectively (p < 0.01); however, injection of normal saline, D-AP5, and PDTC did not cause any significant change (p > 0.05). The suppressive effect of NaHS on gastrointestinal motility and the promotional effect of NaHS on gastric acid secretion could be prevented by D-AP5, a specific N-methyl-D-aspartic acid (NMDA) receptor antagonist, and PDTC, an NF-κB inhibitor. Conclusion: There are neurons co-expressing CBS and c-Fos in the PVN, and the injection of NaHS into the PVN can inhibit gastric motility and promote gastric acid secretion in rats. This effect may be mediated by NMDA receptors and the NF-κB signalling pathway.

Psidium guajava leaf extract improves gastrointestinal functions in rats and rabbits: an implication for ulcer and diarrhoea management

Purpose Psidium guajava L. (Family, Myrtaceae) is reportedly used in ethnomedicine for the treatment of diarrhoea, inflammation, and gastroenteritis. Objective This study evaluated the gastrointestinal function of Psidium guajava leaf extract (PGLE) in rats and rabbits. Materials and methods Crude ethanolic PGLE was subjected to phytochemical and toxicity tests (acute and sub-acute). Standard analytical procedures were employed to evaluate the in vivo gastrointestinal motility, and gastroprotective effect of PGLE against aspirin-induced ulcers. Results In the phytochemical analysis, phenols were the highest (48.32 mg) followed by flavonoids (32.74 mg) and least in tannins (7.31 mg). The acute toxicity of PGLE was >6000 mg/kg. Administration of PGLE decreased significantly (p < 0.05) the body weight, while the liver biomarkers were not significantly altered (p > 0.05) when compared to the control. PGLE significantly increased extractible mucus weight and lowered gastric acid secretion in rats (p < 0.05). PGLE decreased significantly (p < 0.05) ulcer scores and indexes, and increased percentage ulcer inhibition in a dose-dependent manner compared to the negative and omeprazole-treated groups. PGLE dose-dependently inhibited basal amplitudes of contractions, and significantly inhibited acetylcholine-induced contractions, terminating them completely at higher doses. Conclusion PGLE may be a good anti-ulcer and anti-diarrhoeal agent, raising the prospect of novel drug development for such applications.

Hydrogen sulfide in the nucleus tractus solitarii regulates gastric acid secretion in rats.

Hydrogen sulfide (H2S) is a neuromodulator in the central nervous system. The physiological function of H2S in the nucleus tractus solitarii (NTS) has rarely been reported. This research aimed to explore the role of H2S in regulating gastric functions. Wistar rats were randomly assigned to sodium hydrosulfide (NaHS; 4 and 8 nmol) groups, physiological saline (PS) group, capsazepine (10 pmol) + NaHS (4 nmol) group, L703606 (4 nmol) + NaHS (4 nmol) group, and pyrrolidine dithiocarbamate (4 nmol) + NaHS (4 nmol) group. The pH values of gastric acid were measured using a pH meter pre- and post-injection. It was found that the microinjetion of NaHS (4 and 8 nmol), an exogenous H2S donor, into the NTS (n = 6) remarkably decreased the pH values of gastric juice. The inductive effect of NaHS on gastric juice production could be suppressed by capsazepine (a transient receptor potential vanilloid 1 antagonist), L703606 (a NK1 receptor antagonist) and pyrrolidine dithiocarbamate (a nuclear fator-κB inhibitor). However, the same amount of PS did not induce any significant change in the pH value of gastric acid (P > 0.05). The findings of this study revealed that NaHS within the NTS remarkably promoted gastric acid secretion via the activation of TRPV1 channels and nuclear factor-κB-dependent mechanism in rats.

Hydrogen sulfide modulates gastric acid secretion in rats via involvement of substance P and nuclear factor-κB signaling.

Hydrogen sulfide (H2S) promotes gastric acid secretion in rats. The present study aimed to test the hypothesis that H2S regulates this response via activating TRPV1 channel and through activation of the nuclear factor-κB (NF-κB) pathway. Male Wistar rats were randomly divided into the sodium hydrosulfide (NaHS, 100 μmol/kg b.w.) group, pyrrolidine dithiocarbamate (PDTC, 100 μmol/kg b.w.) group, PDTC (100 μmol/kg b.w.) + NaHS (100 μmol /kg b.w.) group, capsazepine (0.1 mM) + NaHS (100 μmol /kg b.w.) group and L703606 (0.1 mM) + NaHS (100 μmol /kg b.w.) group. The acidity of gastric juice before injection and after injection were determined by a pH meter. The results showed that sodium hydrosulfide (NaHS), an exogenous H2S donor, significantly reduced the pH of gastric juice when injected into the enterocoelia. Further, the promotional effect of NaHS on gastric acid secretion could be attenuated by capsazepine, a transient receptor potential vanilloid 1 (TRPV1) antagonist; L703606, a neurokinin 1 (NK1) receptor antagonist; and PDTC, a NF-κB inhibitor. The data from these experiments suggest that NaHS exerts an excitatory effect on gastric acid secretion possibly mediated by TRPV1 channel activation in sensory nerve terminals with the consequent release of substance P and in a NF-κB -dependent manner.

Anti-Gastric Ulcer Activity of the Water Extract from Payawanorn (Pseuderanthemum Palatiferum)

Objective: To examine the anti-gastric ulcer activity of Payawanorn (Psuderanthemum palatiferum) water extract (PPE) in rats.Material and Methods: Evaluation of anti-gastric ulcer activity of PPE was performed using three induced gastric ulcers models: (1) ethanol/hydrochloric acid (EtOH/HCl), (2) restraint water immersion stress and (3) indomethacin. Ulcer indices were determined by microscopic examination (10X). Pylorus ligation and gastric-wall mucus determination were used to investigate the mechanism of anti-gastric ulcer activity of PPE.Results: Oral administration of PPE (150, 300 and 600 mg/kg) significantly inhibited gastric ulcer formation induced by EtOH/HCl, by water immersion restraint stress, and by indomethacin in rats (p-value&lt;0.05). PPE at 600 mg/kg showed a high percent inhibition of gastric ulcer formation in all models. In the pylorus-ligated model, pretreatment with PPE had no effect on pH, acidity output or the gastric acid secretion rate, demonstrating that PPE lacks an anti-secretory effect. Gastric wall mucus was markedly preserved by pretreatment PPE at 600 mg/kg (18.91±2.57 μg alcian blue/g wet stomach) after ethanol-induced ulcer when compared to that the control group (12.38±1.02 μg alcian blue/ g wet stomach).Conclusion: PPE possesses an anti-gastric ulcer effect related to the preservation of gastric mucus, supporting the traditional use of P. palatiferum to treat gastric ulcers.

Anti-Gastric Ulcer Activity of the Water Extract from Payawanorn (Pseuderanthemum Palatiferum)

Objective: To examine the anti-gastric ulcer activity of Payawanorn (Psuderanthemum palatiferum) water extract (PPE) in rats.Material and Methods: Evaluation of anti-gastric ulcer activity of PPE was performed using three induced gastric ulcers models: (1) ethanol/hydrochloric acid (EtOH/HCl), (2) restraint water immersion stress and (3) indomethacin. Ulcer indices were determined by microscopic examination (10X). Pylorus ligation and gastric-wall mucus determination were used to investigate the mechanism of anti-gastric ulcer activity of PPE.Results: Oral administration of PPE (150, 300 and 600 mg/kg) significantly inhibited gastric ulcer formation induced by EtOH/HCl, by water immersion restraint stress, and by indomethacin in rats (p-value&lt;0.05). PPE at 600 mg/kg showed a high percent inhibition of gastric ulcer formation in all models. In the pylorus-ligated model, pretreatment with PPE had no effect on pH, acidity output or the gastric acid secretion rate, demonstrating that PPE lacks an anti-secretory effect. Gastric wall mucus was markedly preserved by pretreatment PPE at 600 mg/kg (18.91±2.57 μg alcian blue/g wet stomach) after ethanol-induced ulcer when compared to that the control group (12.38±1.02 μg alcian blue/ g wet stomach).Conclusion: PPE possesses an anti-gastric ulcer effect related to the preservation of gastric mucus, supporting the traditional use of P. palatiferum to treat gastric ulcers.

Sodium hydrosulfide upregulates mRNA and protein expression of TGF-α in gastric mucosa in experimental model of stimulated gastric acid secretion in rats.

Objective(s):Transforming growth factor alpha (TGF-α) has been shown to modulate the gastric acid secretion. Therefore, the aim of the present study was to investigate the effect of sodium hydrosulfide (NaHS) on TGF-α expression in gastric mucosa in rats.Materials and Methods:Eighteen rats were randomly divided into 3 groups (6 per group). To determine the effect of NaHS on gene and protein expression of TGF-α in gastric mucosa in response to gastric acid, the acid output induced by gastric distension. At the end of experiment, rats were euthanized by anesthetics, and gastric effluents, in addition to mucosa were collected to measure the pH of gastric effluents and to quantify protein and gene expression of TGF-α.Results:The stimulated gastric acid upregulated expression levels of TGF-α in gastric mucosa. These levels were higher in animals pretreated with NaHS.Conclusion:TGF-α upregulatory effect of sodium hydrosulfate implied that TGF-α is involved in the acid inhibitory effect of NaHS.

KFP-H008 blocks gastric acid secretion through inhibiting H+-K+-ATPase

1-(5-(1H-indol-5-yl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine (KFP-H008)，a novel and potent potassium-competitive acid blocker for the treatment of acid secretion related diseases, has not been reported previously. In this study, we demonstrated that KFP-H008 inhibits basal acid secretion, 2-deoxy-D-glucose- (2DG-) stimulated gastric acid secretion in rats. KFP-H008 blocked histamine-stimulated acid secretion in rats and heidenhain pouch dogs and reversed acid output in isolated gastric perfusion under histamine stimulation. In all the animal experiments, KFP-H008 exerted a more effective, potent and longer-lasting inhibitory action in comparison with lansoprazole, a proton pump inhibitor (PPI) commonly used in clinic. KFP-H008 inhibited H+-K+-ATPase activity both at pH 6.5 and pH 7.5, and was unaffected by pH. The inhibitory action was reversible and was achieved in a K+-competitive manner. Furthermore, KFP-H008 did not affect Na+-K+-ATPase activity, thus exhibiting high selectivity, which is different from PPIs. In all, KFP-H008, a novel potassium-competitive acid blocker, may provide new option for the patients with acid-related diseases and provide longer-lasting inhibitory action than drugs commonly used in clinical treatment.

Discovery, synthesis, and structure-activity relations of 3,4-dihydro-1H-spiro(naphthalene-2,2′-piperidin)-1-ones as potassium-competitive acid blockers

With the aim to discover a gastric antisecretory agent more potent than the existing proton pump inhibitors, novel 3,4-dihydro-1H-spiro(naphthalene-2,2′-piperidin)-1-one derivatives, which could occupy two important lipophilic pockets (described as LP-1 and LP-2) of H+,K+-ATPase and can strongly bind to the K+-binding site, were designed based on a docking model. Among the compounds synthesized, compound 4d showed a strong H+,K+-ATPase-inhibitory activity and a high stomach concentration in rats, resulting in potent inhibitory action on histamine-stimulated gastric acid secretion in rats. Furthermore, 4d exerted significant inhibitory action on histamine-stimulated gastric-acid secretion in rats with a rapid onset and moderate duration of action after the administration. These findings may lead to a new insight into the drug design of potassium-competitive acid blockers.

Effect of sodium hydrosulfide on mRNA expression of prostaglandin E2 receptors in response to mucosal acidification and distention-induced gastric acid secretion in rats.

Objective(s):Prostaglandins have been shown to mediate the gastro-protective effect of sodium hydrosulfide (NaHS) but effect of NaHS on mRNA expression of prostaglandin E2 receptors (EP1, 3-4; EPs) has not been investigated. Therefore, this study designed to evaluate the effect of NaHS on mRNA expression of EPs receptors in response to mucosal acidification and distention-induced gastric acid secretion in rats.Materials and Methods:Fasted rats were randomly assigned into 4 groups (n=6/group). They were control, and NaHS-treated groups. To evaluate the effect of NaHS on mucosal mRNA expression of EPs receptors, the gastric mucosa exposed to stimulated gastric acid output and mucosal acidification. The pylorus sphincter catheterized for instillation of isotonic neutral saline or acidic solution. Ninety min after beginning the experiments, animals sacrificed and the gastric mucosa collected to determine the pH, mucus secretion and to quantify the mRNA expression of EPs receptors by quantitative real-time PCR.Results:present results showed that a) NaHS increased the mucus secretion, mRNA expression of EP3 and EP4 receptors in response to distention-induced expression; b) The mRNA expression of EP1 receptors increased while EP4 mRNA receptors decreased in response to mucosal acidification in NaHS-pretreated rats; and c) NaHS increased pH of gastric contents both in response to distention-induced gastric acid secretion and mucosal acidification.Conclusion:NaHS behaves in a different manner. It effectively only increased the pH of gastric contents to reinforce the gastric mucosa against a highly acidic solution but modulated both acid and mucus secretion when the rate of acid increase in the stomach was slower.

Role of hydrogen sulfide within the dorsal motor nucleus of the vagus in the control of gastric function in rats.

Hydrogen sulfide (H2 S) is a gaseous messenger and serves as an important neuromodulator in the central nervous system. This study aimed to clarify the role of H2 S within the dorsal motor nucleus of the vagus (DMV) in the control of gastric function in rats. Cystathionine β-synthetase (CBS) is an important generator of endogenous H2 S in the brain. We investigated the distribution of CBS in the DMV using immunohistochemical method, and the effects of H2 S on gastric motility and on gastric acid secretion. CBS-immunoreactive (IR) neurons were detected in the rostral, intermediate and caudal DMV, with the highest number of CBS-IR neurons in the caudal DMV, and the lowest in the intermediate DMV. We also found that microinjection of the exogenous H2 S donor NaHS (0.04 and 0.08 mol/L; 0.1 μL; n = 6; p < 0.05) into the DMV significantly inhibited gastric motility with a dose-dependent trend, and promoted gastric acid secretion in Wistar rats. Microinjection of the same volume of physiological saline (PS; 0.1 μL, n = 6, p > 0.05) at the same location did not noticeably change gastric motility and acid secretion. The data from these experiments suggest that the CBS that produces H2 S is present in the DMV, and microinjection of NaHS into the DMV inhibited gastric motility and enhanced gastric acid secretion in rats.

Перспектива застосування агоністів PPARγ меланіну та піоглітазону при тривалій гіпоацидності шлунка

It was investigated the effects of agonists of nuclear receptors peroxisome proliferator-activated receptors gamma (PPARγ) melanin and pioglitazone оn the secretory function of the stomach in rats under long hypoacidity of gastric juices caused bу the introduction of Н+-К+- ATPase blocker omeprazole during 28 days. As а result of studies it was found that administration of omeprazole for 28 days leads to increase of hydrochloric acid secretion of stomach, resulting in the development of hypergastrinemia. Activation of PPARy Bу pioglitazone and melanin in the conditions of the development of experimental hypergastrinemia prevents the hypertrophy of the gastric mucosa and decreases debit of the basal gastric acid secretion in rats.

Inhibition of Histamine-Stimulated Gastric Acid Secretion by Hydrogen Sulfide in Male Rats

Recently, hydrogen sulfide (H_2S) introduces as the third gaseous transmitter that has many physiologic and pharmacologic roles in the body. The aim of the present study was to investigate the effect of exogenously given H_2S on histamine-induced gastric acid secretion in rats. Thirtytwo male Wistar rats (150-200 g) were randomly assigned into 4 groups (8 per group). Animals were deprived of food but not water 24 h before the experiment and were randomly assigned into two control groups, distention-, and histamine-stimulated groups, and two NaHS-treated groups. To evaluate the effect of H_2S on histamine-induced gastric acid secretion, one group of animals were received an I.V. bolus of NaHS (a H_2S donor) at 80 μg/kg. To investigate the possible involved mechanism of the antisecretory effect of NaHS, mRNA expression of histidine decarboxylase (HDC) were evaluated by reverse-transcriptase PCR. The gastric acid output in response to histamine decreased by NaHS treatment (P＜0.01). Also the results showed that the level of gene expression of HDC was higher in NaHS-treated group than in control rats. The findings showed that the inhibitory effect of H_2S on gastric acid secretion was not related to a decrease in histamine release. It seems that up-regulation of HDC mRNA expression is secondary to inhibition of gastric acid secretion by NaHS.

Sa2024 Involvement of Gastric Secretion and Primary Capsaicin-Sensitive Afferent Nerves in the Gastroprotection Induced by Hydrogen Sulfide in Rat Stomach

Hydrogen sulfide (H2S) modulates a number of physiological actions including vasodilatation, inhibition of oxidant stress and apoptosis. H2S which is formed in gastric epithelium by the activity of two enzymes cysthationine γ-lyase (CSE) and cystathionine β-synthetase (CBS) has been shown to protect the gastric mucosa from ethanol-induced gastric lesions but whether its efficacy against acid-dependent stress-induced damage has been little studied. It also remains unknown how the expression of CSE and CBS contribute to the mucosal damage induced by stress in the presence or absence of H2S. We studied the effect of NaHS, a H2S-donor and L-cysteine, a H2S precursor on 1) gastric acid secretion in rats equipped with chronic gastric fistulas (GF) and water immersion restraint stress (WRS)-induced gastric lesions with intact and capsaicin-denervated sensory nerves (large dose 125 mg/kg s.c for 3 days). Rats were pretreated 30 min before the WRS with A) NaHS (5 mg/kg i.g); B) Lcysteine (10 mg/kg i.g.) with or without the combination with inhibitors of CSE activity, beta-cyano-L-alanine (BCA, 50 mg/kg i.g.) and D,L-propargylglycine (PAG 15 80 mg/kg i.g.). The number of gastric lesions was measured by planimetry, the gastric blood flow (GBF) by H2-gas clearance technique and the mRNA expression of CSE, CBS, HIF-1 α and antioxidizing enzymes SOD and GPx was assessed by RT-PCR and Western Blot. NaHS (120 mg/kg) and cysteine (5-40 mg/kg) dose-dependently inhibited basal and histaminestimulated gastric acid secretion in GF rats. Exposure to WRS caused mucosal hemorrhagic lesions accompanied by the fall in GBF and upregulation of mRNA expression of CSE and CBS. Pretreatment with NaHS and L-cysteine significantly reduced WRS-induced gastric damage and significantly raised GBF and these effects were completely lost in animals with capsaicin denervation. BCA and PAG which dose-dependently augmented the number of WRS lesions, reversed the NaHS and L-cysteine-induced protection and hyperemia against WRS-induced gastric damage. Upregulation of mRNA expression for HIF-1 α mRNA, CSE and CBS in the gastric mucosa exposed to WRS was diminished by NaHS and L-cysteine and these effects were further enhanced in capsaicin-denervated rats treated with NaHS and L-cysteine. The increased expression of SOD and GPx mRNA was observed in NaHSand L-cysteine-pretreated rats but not in those with capsaicin-denervation. We conclude that: 1) an increase in the expression of CSE and CBS, key enzymes in H2S biosynthesis, could compensate for the stress-induced impairment of gastric mucosal defense; 2) antisecretory activity of H2S donors contributes to the attenuation of acid-dependent injury caused by WRS, and 3) sensory mediators and antioxidizing enzymes SOD and GPx play an important role in H2S-induced gastroprotection against WRS-induced ulcerogenesis.

Effect of Nesfatin-1 on gastric acid secretion in rats

Effect of Nesfatin-1 on gastric acid secretion in rats

Role of Nitric Oxide in the Central Interferon-alpha-induced Inhibition of Gastric Acid Secretion in Rats

Cytokines are known to play a key role in regulation of gastric functions. Interferon-alpha (IFN-α) has been published to impair gastric motility. Aims of this study were to clarify effect of IFN-α on gastric acid secretion (GAS) and determine role of nitric oxide (NO) in the process. Both subcutaneous (1000, 10000, 100 000 IU, s.c.) and intracisternal (10, 100, 1000 IU, i.c.) injections of IFN-α dose-dependently inhibited GAS induced by pylorus ligation in male SD rats in 2 hrs (370±40, 233±39, 208±50 micromol vs control 415±59 micromol and 481±50, 249±75, 141±25 micromol vs control 485±65 micromol, respectively). Central doses inducing same level inhibition were 100 times lower. NOS inhibitor L-NAME (3 mg/kg, i.v.) blocked the inhibitory effect of i.c. ED(50) dose 100 IU IFN-α (507±75 micromol/2 hrs), while L-arginine, the substrate of nitric oxide synthase (NOS) prevented L-NAME action (266±82 micromol/2 hrs). D-arginine failed to prevent L-NAME action on IFN-α-induced inhibition of GAS. Aminoguanidine, a selective inhibitor of inducible NOS (iNOS) failed to block IFN-α induced inhibition of GAS. Results suggest that IFN-α inhibits GAS centrally through nitric oxide pathways probably mediated by continuous isoform of NOS that can be important in regulation of GAS in healthy or pathological conditions.

Role of Nitric Oxide in the Central Interferon-alpha-induced Inhibition of Gastric Acid Secretion in Rats

Cytokines are known to play a key role in regulation of gastric functions. Interferon-alpha (IFN-α) has been published to impair gastric motility. Aims of this study were to clarify effect of IFN-α on gastric acid secretion (GAS) and determine role of nitric oxide (NO) in the process. Both subcutaneous (1000, 10000, 100 000 IU, s.c.) and intracisternal (10, 100, 1000 IU, i.c.) injections of IFN-α dose-dependently inhibited GAS induced by pylorus ligation in male SD rats in 2 hrs (370±40, 233±39, 208±50 micromol vs control 415±59 micromol and 481±50, 249±75, 141±25 micromol vs control 485±65 micromol, respectively). Central doses inducing same level inhibition were 100 times lower. NOS inhibitor L-NAME (3 mg/kg, i.v.) blocked the inhibitory effect of i.c. ED50 dose 100 IU IFN-α (507±75 micromol/2 hrs), while L-arginine, the substrate of nitric oxide synthase (NOS) prevented L-NAME action (266±82 micromol/2 hrs). D-arginine failed to prevent L-NAME action on IFN-α-induced inhibition of GAS. Aminoguanidine, a selective inhibitor of inducible NOS (iNOS) failed to block IFN-α induced inhibition of GAS. Results suggest that IFN-α inhibits GAS centrally through nitric oxide pathways probably mediated by continuous isoform of NOS that can be important in regulation of GAS in healthy or pathological conditions. Keywords: Brain-gut interactions, cytokines, NOS inhibitors, iNOS, cNOS, peripheral and central interferon-alpha action, vago-vagal reflex, central nervous system, pylorus ligation, D-arginine

From Bedside to Bench: Reverse Engineering Medical Progress

From Bedside to Bench: Reverse Engineering Medical Progress