Biomedical subjects

Richard F Harty

Publications and source records attributed to Richard F Harty.

10 recordsLinked to original sources

PubMed2006

Inhibition of epidermal growth factor receptor activation enhances in vivo histamine-stimulated gastric acid secretion in the rat.

Epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha) have been shown to inhibit gastric acid secretion through stimulation of the EGF receptor (EGFR). In this study we examined in vivo the effects of inhibition of the EGFR on histamine-stimulated acid secretion in the rat. Submaximal (1.5 mg/kg/hr) histamine-stimulated acid secretion was measured (microEq H(+)/2 hr) during infusion of EGFRtk inhibitors and ranitidine in anesthetized rats. EGFR phosphorylation in gastric mucosal tissue lysates was measured by Western blot analysis. Submaximal histamine-stimulated acid secretion was increased significantly by the EGFR inhibitors tyrphostin (Tyr) A46 and Tyr AG1478. Tyr A46 prevented TGFalpha (10 microg/kg/hr)-mediated inhibition of maximal (5.0 microg/kg/hr) histamine-stimulated acid output. Histamine caused a fourfold increase in EGFR phosphorylation which was inhibited by both Tyr and ranitidine. We conclude that the EGFRtk inhibitors, Tyr A46 and Tyr AG1478, significantly increased submaximal histamine-stimulated acid output and Tyr A46 prevented TGFalpha inhibition of histamine-stimulated acid secretion. These observations suggest that the EGFR is involved, in vivo, in the regulation of gastric acid secretion.

Animals↗

PubMed2006

Antioxidant therapy with N-acetylcysteine plus mesalamine accelerates mucosal healing in a rodent model of colitis.

The aims of this study were to examine the ability of the antioxidant N-acetylcysteine (NAC) and mesalamine (5-ASA) alone and in combination to affect TNBS-induced colitis in rat. Three days following induction of TNBS colitis rats were randomized to receive daily intracolonic treatment with NAC, 5-ASA, and NAC plus 5-ASA for 5 or 8 days. At the end of the treatment period macroscopic and microscopic colonic injuries were scored. Myeloperoxidase (MPO) activity and cytokine gene expression were measured in colonic tissues. Results indicated that treatment with NAC plus 5-ASA caused a significantly greater reduction in colonic injury than either agent alone. Furthermore, combination therapy inhibited significantly MPO activity and inflammatory cytokine gene expression in the distal colon of TNBS-treated animals. The beneficial effects of NAC plus 5-ASA on reduction of colonic injury and promotion of healing were most evident after 8 days of treatment.

Acetylcysteine↗

PubMed2006

Stress ulcer bleeding.

Although upper gastrointestinal (GI) bleeding from stress-related mucosal disease (SRMD) in critically ill patients is common, significant bleeding with hemodynamic instability is not. Risk factor assessment can assist in identifying patients with a greater likelihood of developing significant SRMD. Prophylaxis against stress ulcer bleeding with luminal agents (eg, antacids and sucralfate) or drugs that inhibit acid secretion (eg, histamine 2-receptor antagonists and proton-pump inhibitors) can reduce major bleeding but has little or no effect on mortality. Currently, the mainstays of prophylactic therapy for SRMD are intravenously administered H2RAs and PPIs. Wider usage of PPIs reflects their enhanced efficacy in suppressing acid secretion as well as lack of tolerance for H2RAs. Guidelines for the prophylactic use of H2RAs or PPIs in treatment of SRMD will require large, randomized studies that also examine cost effectiveness of individual strategies.

Journal Article↗

PubMed2005

Sporadic colonic hamartomas in adults: a retrospective study.

BACKGROUND: Colonic hamartomas are uncommon in adults. The aims of this study were to determine (1) the prevalence of colonic hamartomas in an adult population undergoing colonoscopy and (2) the clinical, endoscopic, and histologic features of colonic hamartomas in adult patients. METHODS: A pathology database identified 19 adult patients of 12,707 patients with colonic hamartomas in the 11-year study period from January 1992 to October 2002. An endoscopic computer database provided information about the number of colonoscopies performed and the presence or the absence of colonic polyp(s) in study patients. Charts of patients with colonic hamartomas were reviewed, and clinical and demographic data were collated. RESULTS: Nineteen patients were found to have colonic hamartomas. The mean age of these patients was 55 years, with an age distribution ranging from 25 to 81 years. The prevalence of colonic hamartomas in this study population was 0.15%. The prevalence of hamartomas in patients with colon polyps at index colonoscopy was 0.073%. Colonic hamartomas were more common in men than in women. The indication for colonoscopy for the majority (68%) of patients was hematochezia or the presence of occult blood in the stool. Three fourths of the polyps were greater than 1 cm in diameter, and 89% were pedunculated. Two thirds of the hamartomatous polyps were localized to the rectosigmoid region. Endoscopic characteristics of hamartomas were indistinguishable from adenomas. CONCLUSIONS: Colonic hamartomas in adults are rare. They tend to be single, pedunculated, and localized predominantly in the rectosigmoid region. Endoscopic resection of colonic hamartomas was successful in all patients.

Adult↗

PubMed2004

Functional interaction between transforming growth factor alpha and capsaicin-sensitive sensory neurons in the rat stomach.

BACKGROUND AND AIMS: Transforming growth alpha (TGFalpha) and sensory neurons have been shown to promote gastric mucosal protection and healing. Aims were to examine in vitro interactions between gastric sensory neurons, the sensory neuropeptide calcitonin gene-related peptide (CGRP), and TGFalpha. METHODS: Gastric mucosal/submucosal tissue fragments from Sprague-Dawley (SD) rats were incubated in short-term (30 min) culture. Peptide release into media and TGFalpha tissue content were measured by radioimmunoassay. RESULTS: TGFalpha (1 x 10(-8) to 1 x 10(-6) M) caused dose-dependent stimulation of CGRP release. Maximal CGRP release (+87%) was observed with 1 x 10(-6) M TGFalpha: 28.6+/-3.8 vs. control of 15.5+/-2.7 pg/g tissue; P<0.05. Both CGRP (1 x 10(-7) to 1 x 10(-5) M) and capsaicin (1 x 10-(8) to 1 x 10(-6)M) significantly inhibited basal TGFalpha release in a dose-dependent fashion that ranged from -20% to -39%. In contrast, capsaicin-induced sensory denervation caused significant increases in both basal TGFalpha release and TGFalpha tissue content. CONCLUSION: Function interactions between TGFalpha and gastric sensory neurons are suggested by the observations that (1) TGFalpha stimulated CGRP release from gastric sensory neurons; (2) CGRP and acute capsaicin treatment inhibited TGFalpha release and; (3) capsaicin-induced sensory denervation caused significant increases in both gastric TGFalpha basal release and tissue content.

Animals↗

PubMed2003

Transforming growth factor alpha-mediated gastroprotection against stress ulceration in the rat: involvement of capsaicin-sensitive sensory neurons.

Exogenously administered TGF alpha has been shown to protect rodent gastric mucosa against injury caused by acid-dependent and acid-independent injury. The present study examined whether the gastroprotective effects of TGF alpha on stress-induced gastric ulceration in the rat involves activation of capsaicin-sensitive sensory neurons. Fasted male SD rats were subjected to water restraint stress (WRS) for four hours. Thereafter, rats were euthanized; the stomach opened and macroscopic areas of gastric ulceration quantitated (mm(2)). Gastric tissue contents of TGF alpha and the sensory neuropeptide, calcitonin gene-related peptide (CGRP) were determined by radioimmunoassay. Prior to stress rats received TGF alpha 50, 100 or 200 microg/kg by intraperitoneal injection. Sensory denervation was accomplished by high dose capsaicin treatment. WRS caused severe ulceration in the gastric corpus; 46.1 + 6.6 mm(2). Parenteral administration of TGF alpha caused dose-dependent reduction in gastric injury: 34.7 + 4.9 mm(2) with 50 microg/kg (p < 0.05); 25.4 + 3.6 mm(2) with 100 microg/kg (p < 0.001) and 9.4 + 0.8 mm(2) with 200 microg/kg (p < 0.001). The gastroprotective action of TGF alpha (200 microg/kg, i.p.) was abolished by capsaicin-induced sensory denervation. In addition, WRS ulceration was associated with significant reduction in gastric CGRP (-42%) and TGF alpha (-48%) content. Reduction in CGRP content was prevented by TGF alpha pretreatment. We conclude that: 1) TGF alpha caused dose-dependent gastroprotection against WRS ulceration, 2) TGF alpha-mediated gastric mucosal protection was prevented by capsaicin-induced sensory denervation and, 3) stress-induced injury was associated with significant reduction in gastric content of both TGF alpha and CGRP.

Animals↗

PubMed2003

Somatostatin-induced gastric protection against ethanol: involvement of nitric oxide and effects on gastric mucosal blood flow.

BACKGROUND/AIMS: The mechanisms of somatostatin-mediated gastroprotection are not fully understood. Aims of this study were to determine in the rat the role of nitric oxide (NO) in somatostatin-induced effects on gastric mucosal protection and blood flow (GMBF) in the absence and in the presence of intraluminal ethanol. METHODS: Ethanol (70% v/v)-induced gastric mucosal injury after orogastric dosing was quantitated at 30 min and GMBF determined in an ex vivo gastric chamber preparation. RESULTS: Somatostatin (4 microg/kg; i.p.) protection against ethanol-induced ulceration was prevented by the NO inhibitor L-NNA and restored by L-arginine, but not D-arginine. Somatostatin (1-8 microg/kg; i.p.) did not effect basal GMBF. The gastroprotective dose of somatostatin (4 microg/kg; i.p.) prevented the decrease in GMBF caused by ethanol. L-NNA reversed this vascular effect of somatostatin. CONCLUSION: Somatostatin-induced gastroprotection and restoration of GMBF during ethanol exposure involve mechanisms which are dependent on NO generation.

Administration, Oral↗

PubMed2003

Mechanisms of transforming growth factor-alpha (TGF-alpha) induced gastroprotection against ethanol in the rat: roles of sensory neurons, sensory neuropeptides, and prostaglandins.

The mechanisms by which transforming growth factor-a (TGP-alpha) protects the stomach against mucosal injury are incompletely understood. The aim of this study was to examine the roles of sensory neurons, sensory neuropeptides and prostaglandins in TGFalpha gastroprotection against ethanol. Fasted rats received TGF-alpha (50 microg/kg, intraperitoneally) prior to orogastric ethanol (75% v/v, 1 ml). Gastric injury was quantitated 30 min after ethanol. Involvement of sensory neurons and the sensory neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), were examined by capsaicin deafferentation and specific receptor antagonist infusion, respectively. Indomethacin (10 mg, intragastrically) was used to determine the role of prostaglandins in TGF-alpha-mediated gastroprotection. TGF-alpha significantly diminished ethanol-induced gastric lesion area to 5.7 +/- 0.8 mm2 vs 41.1 +/- 5.2 mm2 (p < 0.001). Sensory denervation and CGRP-receptor blockade abolished the TGF-alpha protective effect. In contrast, SP antagonist and indomethacin did not alter TGF-alpha gastroprotection. In conclusion, TGF-alpha-mediated gastroprotection involves sensory neuron activation and CGRP release and this protective effect did not involve substance P or prostaglandin generation.

Analysis of Variance↗

PubMed2003

Primary aortoenteric fistula to jejunum: a case report.

Primary aortoenteric fistula (PAEF) is a well-known but rare cause of gastrointestinal bleeding. The diagnosis can be difficult since the majority of patients do not have classical symptoms. "Herald bleed" is usually followed by a massive hemorrhage. Endoscopy and radiographic studies can assist in diagnosis. We present the case of 56-year-old male with PAEF who presented with obscure gastrointestinal bleeding. Endoscopic studies were unremarkable. Computed tomography (CT) in this stable but symptomatic patient helped in establishing diagnosis of PAEF. Patient underwent laparotomy with aortobifemoral graft placement. A high index of suspicion, early diagnosis and prompt appropriate surgical intervention are crucial for survival of these patients.

Aortic Aneurysm, Abdominal↗

PubMedDate not supplied

GABAergic mechanisms of gastroprotection in the rat: role of sensory neurons, prostaglandins, and nitric oxide.

gamma-Aminobutyric acid (GABA) is a neurotransmitter found in both the central and the peripheral nervous systems including the gastrointestinal tract. The aims of the present studies were to examine mechanisms by which GABA exerts gastroprotective effects against ethanol- and water-restraint stress (WRS)-induced gastric mucosal injury in the rat. GABA, administered intragastrically (400 mg/kg), induced gastroprotection against ethanol and WRS by activating gastric sensory neurons to release calcitonin gene-related peptide (CGRP) and promote nitric oxide (NO) synthesis and release. Furthermore, these protective effects of GABA were associated with an increase in gastric mucosal blood flow (GMBF) that was dependent on sensory neuron and NO systems. GABA-mediated protection involved GABAA receptor activation and prostaglandin generation. In conclusion, intraluminal GABA protects the stomach against ethanol- and WRS-induced injury by mechanisms which involve sensory neuron/CGRP/NO pathways and increases in GMBF and prostaglandin generation.

Animals↗