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Jaśkowski BM, Opałka A, Gehrke M, Herudzińska M, Czeladko J, Baumgartner W, Jaśkowski JM. A Critical Overview on Prostaglandin Inhibitors and Their Influence on Pregnancy Results after Insemination and Embryo Transfer in Cows. Animals (Basel) 2021; 11:ani11123368. [PMID: 34944145 PMCID: PMC8697890 DOI: 10.3390/ani11123368] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 11/12/2021] [Accepted: 11/22/2021] [Indexed: 12/22/2022] Open
Abstract
Simple Summary Assisted reproductive techniques, such as artificial insemination or embryo transfer have been used in cattle reproduction for decades, but despite many methodological improvements, pregnancy rates have not increased proportionately. One strategy to improve the pregnancy rate after artificial insemination and embryo transfer is to increase the chance of early embryo survival with the use of medications such as nonsteroidal anti-inflammatory drugs. This paper compares the effect of the application of the most frequently used nonsteroidal anti-inflammatory drugs in cattle (flunixin meglumine, carprofen, meloxicam, ibuprofen, aspirin, and sildenafil), as well as of steroid drugs that are used less frequently in cattle reproduction. An evaluation of published reports revealed a range of outcomes that were not always consistent with each other. However, a positive effect of nonsteroidal anti-inflammatory drug treatment on the pregnancy rate in cattle was indicated, especially with the use of flunixin meglumine. Abstract Assisted reproductive techniques in cattle, such as artificial insemination (AI) and embryo transfer (ET), are widely used. Despite many years of methodological improvements, the pregnancy rate (PR) in cows has not increased in direct proportion with their development. Among the possibilities to increase the PR is the use of certain steroids and nonsteroidal anti-inflammatory drugs (NSAIDs). The antiluteolytic effect of NSAIDs is achieved by blocking cyclooxygenase, which is involved in the conversion of arachidonic acid to prostaglandins. This article compares the PRs obtained after treatment with the commonly used NSAIDs in cattle, including flunixin meglumine, carprofen, meloxicam, ibuprofen, aspirin, and sildenafil. Studies on the effectiveness of certain steroid drugs on the PR have also been described. The results were not always consistent, and so comparisons between studies were made. In conclusion, flunixin meglumine seems to be an option, and can be recommended for improving ET results, especially in situations of high exposure or susceptibility to stress. Its administration under all circumstances, however, might be pointless and will not lead to the desired effect.
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Affiliation(s)
- Bartłomiej M. Jaśkowski
- Department of Reproduction and Clinic of Farm Animals, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50-366 Wroclaw, Poland;
- Correspondence: ; Tel.: +48-71-320-5301
| | - Adam Opałka
- Department of Reproduction and Clinic of Farm Animals, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50-366 Wroclaw, Poland;
| | - Marek Gehrke
- Department of Diagnostics and Clinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University, 87-100 Toruń, Poland; (M.G.); (J.M.J.)
| | - Magdalena Herudzińska
- Department of Basic and Preclinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University, 87-100 Toruń, Poland;
| | | | - Walter Baumgartner
- University Clinic for Ruminants, University of Veterinary Medicine, Veterinaerplatz 1, A-1210 Vienna, Austria;
| | - Jędrzej M. Jaśkowski
- Department of Diagnostics and Clinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University, 87-100 Toruń, Poland; (M.G.); (J.M.J.)
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Koh SJ, Kim JW, Kim BG, Lee KL, Kim JS. Restraint stress induces and exacerbates intestinal inflammation in interleukin-10 deficient mice. World J Gastroenterol 2015; 21:8580-8587. [PMID: 26229400 PMCID: PMC4515839 DOI: 10.3748/wjg.v21.i28.8580] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2015] [Revised: 03/30/2015] [Accepted: 04/09/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effects of restraint stress on chronic colitis in interleukin (IL)-10 deficient (IL-10-/-) mice.
METHODS: The first experiment compared the effect of restraint stress on the development of intestinal inflammation in wild-type and IL-10-/- mice. Both wild-type and IL-10-/- mice were physically restrained in a well-ventilated, 50 cm3 conical polypropylene tube for 2 h per day for three consecutive days. The second experiment was performed to assess the effect of restraint stress on exacerbation of colitis induced by piroxicam in IL-10-/- mice. The IL-10-/- mice were exposed to restraint stress for 2 h per day for 3 consecutive days, and then treated with piroxicam for 4 d at a dose of 200 ppm administered in the rodent chow.
RESULTS: In the first experiment, none of the wild-type mice with or without restraint stress showed clinical and histopathological abnormality in the gut. However, IL-10-/- mice exposed to restraint stress exhibited histologically significant intestinal inflammation as compared to those without restraint stress. In the second experiment, restraint stress significantly reduced body weight and increased the severity of intestinal inflammation assessed by histopathologic grading in IL-10-/- mice. Colonic IL12p40 mRNA expression was strongly increased in mice exposed to restraint stress.
CONCLUSION: This novel animal model could be useful in future study of psychological stress in the pathogenesis of inflammatory bowel disease.
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MESH Headings
- Animals
- Chronic Disease
- Colitis/etiology
- Colitis/genetics
- Colitis/metabolism
- Colitis/pathology
- Colitis/prevention & control
- Colitis/psychology
- Colon/metabolism
- Colon/pathology
- Disease Models, Animal
- Gene Expression Regulation
- Interleukin-10/deficiency
- Interleukin-10/genetics
- Male
- Mice, Inbred C57BL
- Mice, Knockout
- Piroxicam
- RNA, Messenger/metabolism
- Receptors, Interleukin-12/genetics
- Receptors, Interleukin-12/metabolism
- Restraint, Physical
- Stress, Psychological/complications
- Stress, Psychological/metabolism
- Stress, Psychological/psychology
- Time Factors
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3
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Abstract
The structural and functional integrity of the gastric and duodenal mucosa represents equilibrium between aggressive factors and protective mechanisms. Mucus-buffers-phospholipid layer as pre-epithelial barrier, enhanced by prostaglandins and epidermal growth factor, remains a vanguard of mucosal protection. It maintains a neutral pH at the surface epithelial luminal interface, facing luminal pH dropping to 1.0, i.e., hydrogen ion concentration gradient equal 1,000,000. The surface epithelial cells, elaborating mucins, buffers, phospholipids, prostaglandins, trefoil peptides, peptide growth factor and their receptors, heat shock proteins, cathelicidins, and β-defensins form the second line of defense. Endothelium exerts mucosal protection through production of potent vasodilators like nitric oxide and prostacyclins and through release of angiogenic growth factors, securing adequate blood flow and representing the third and an ultimate line of mucosal protection. This microcirculation is instrumental for supply of oxygen, nitric oxide, hydrogen sulfide and removal of ad hoc generated toxic substances as well as for continuous mucosal cell renewal from progenitor cells, secured by growth factors accompanied by survivin preventing early apoptosis.
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Affiliation(s)
- Harathi Yandrapu
- Department of Internal Medicine, Molecular Medicine Research Laboratory, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, 4800 Alberta Avenue, El Paso, TX, 79905, USA,
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4
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Lindquist B, Lingström P, Fändriks L, Birkhed D. Influence of five neutralizing products on intra-oral pH after rinsing with simulated gastric acid. Eur J Oral Sci 2011; 119:301-4. [PMID: 21726291 DOI: 10.1111/j.1600-0722.2011.00841.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The aetiology of dental erosion may be of both extrinsic and intrinsic origin. The aim of the present study was to test the ability of various neutralizing products to raise the low intra-oral pH after an erosive exposure, in this case to gastric acid, which was simulated using hydrochloric acid (HCl). Eleven adults participated. They rinsed with 10 ml of 10 mM HCl (pH 2) or 10 ml of 100 mM HCl (pH 1) for 1 min, after which the pH was measured intra-orally for up to 30 min at four sites (two approximal, one buccal, and the dorsum of the tongue). After rinsing with the two acid solutions (pH 1 and pH 2), the following products were used: (i) antacid tablet; (ii) gum arabic lozenge; (iii) mineral water; (iv) milk; and (v) tap water (positive control). The negative control was no product use. The five test products were used for 2 min after the erosive challenge. All the products produced an initially higher pH compared with the negative control. The antacid tablet resulted in the greatest and most rapid increase in pH, followed by the lozenge. In dental practice, the use of any of the neutralizing products tested, especially the antacid tablet, could be recommended in order to increase the intra-oral pH after an erosive challenge.
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Affiliation(s)
- Birgitta Lindquist
- Department of Cariology, Institute of Odontology, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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5
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Abstract
Peptic ulcer bleeding is one of the most common emergency situations in medicine. Combined pharmacological and endoscopic therapy together with emerging interventional radiological procedures are successfully treating peptic ulcer disease, reserving surgical procedures for only a small portion of patients unresponsive to 'conventional' therapy. Technological advancement has seen a great improvement in the field of endoscopic treatment in the form of various methods of hemostasis. However, pharmacological therapy with proton pump inhibitors still plays the central role in the peptic ulcer bleeding treatment algorithm.
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Affiliation(s)
- D Štimac
- Division of Gastroenterology, Department of Internal Medicine, University Hospital Center Rijeka, School of Medicine, University of Rijeka, Rijeka, Croatia.
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6
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Lindsay KB, Skrydstrup T. Formal Total Synthesis of the Potent Renin Inhibitor Aliskiren: Application of a SmI2-Promoted Acyl-like Radical Coupling. J Org Chem 2006; 71:4766-77. [PMID: 16776501 DOI: 10.1021/jo060296c] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
A formal total synthesis of the potent renin inhibitor aliskiren is disclosed exploiting an alternative coupling strategy recently developed by this laboratory for the preparation of the hydroxyethylene isostere-based class of protease inhibitors. The thioester derivative of the amino acid representing the C5-C9 fragment of the aliskiren carbon skeleton underwent a carbon chain extension via a SmI2-promoted radical addition to n-butyl acrylate. Introduction of the C3-isopropyl group with the correct relative configuration was accomplished via stereoselective reduction of the obtained ketone with concomitant lactonization, followed by an aldol reaction with acetone. Further functional group and protecting group manipulation culminated in a formal total synthesis of aliskiren in 10 steps from the corresponding fully protected non-natural amino acid.
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Affiliation(s)
- Karl B Lindsay
- Center for Insoluble Protein Structures, Department of Chemistry, University of Aarhus, Langelandsgade 140, 8000 Aarhus C, Denmark
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7
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Oginni AO, Agbakwuru EA, Ndububa DA. The prevalence of dental erosion in Nigerian patients with gastro-oesophageal reflux disease. BMC Oral Health 2005; 5:1. [PMID: 15740613 PMCID: PMC554987 DOI: 10.1186/1472-6831-5-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2004] [Accepted: 03/01/2005] [Indexed: 11/25/2022] Open
Abstract
Background In various people of the Western world, gastro-oesophageal reflux (GOR) has been reported to be a common problem. Various studies have also assessed the relationship between GOR and dental erosion. The authors are not aware of such studies in Nigerians. It is therefore the aims of the present study to estimate the prevalence of GOR; to estimate the prevalence of dental erosion in patients with GORD; to document the oral findings in patients diagnosed with GORD and to compare these findings with previous studies elsewhere. Methods A total of 225 subjects comprising of 100 volunteers and 125 patients diagnosed with GORD were involved in this study. History of gastric juice regurgitation and heartburn were recorded. Oral examination to quantify loss of tooth structure was done using the tooth wear index (TWI) designed by Smith and Knight (1984). Results Twenty patients with GORD presented with dental erosion in the maxillary anterior teeth with TWI scores ranging from 1–3. The prevalence of erosion was found to be statistically significant between GORD patients (16%) and control (5%) (p < 0.05), but not significant between endoscopic diagnostic groups (p > 0.05). Conclusion The present study supports the consideration of dental erosion as the extra-oesophageal manifestation of GORD. However the association between GORD and burning mouth sensation needs more investigation.
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Affiliation(s)
- Adeleke O Oginni
- Department of Restorative Dentistry, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Elugwaraonu A Agbakwuru
- Department of Surgery, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Dennis A Ndububa
- Department of Medicine, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria
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Kivelä AJ, Kivelä J, Saarnio J, Parkkila S. Carbonic anhydrases in normal gastrointestinal tract and gastrointestinal tumours. World J Gastroenterol 2005; 11:155-63. [PMID: 15633208 PMCID: PMC4205394 DOI: 10.3748/wjg.v11.i2.155] [Citation(s) in RCA: 115] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Carbonic anhydrases (CAs) catalyse the hydration of CO2 to bicarbonate at physiological pH. This chemical interconversion is crucial since HCO3- is the substrate for several biosynthetic reactions. This review is focused on the distribution and role of CA isoenzymes in both normal and pathological gastrointestinal (GI) tract tissues. It has been known for many years that CAs are widely present in the GI tract and play important roles in several physiological functions such as production of saliva, gastric acid, bile, and pancreatic juice as well as in absorption of salt and water in intestine. New information suggests that these enzymes participate in several processes that were not envisioned earlier. Especially, the recent reports on plasma membrane-bound isoenzymes IX and XII have raised considerable interest since they were reported to participate in cancer invasion and spread. They are induced by tumour hypoxia and may also play a role in von Hippel-Lindau (VHL)-mediated carcinogenesis.
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Affiliation(s)
- Antti-J Kivelä
- Department of Anatomy and Cell Biology, University of Oulu, Finland.
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9
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Van Hoogmoed LM, Harmon FA, Snyder J. Microvascular anatomy of the third compartment of the stomach of llamas. Am J Vet Res 2003; 64:346-50. [PMID: 12661876 DOI: 10.2460/ajvr.2003.64.346] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To characterize the vascular anatomy of the third compartment of the stomach of llamas. ANIMALS 7 adult llamas. PROCEDURE Immediately after each llama was euthanatized, vascular replicas of tissue from the third compartment were prepared by use of methylmethacrylate monomer and catalyst. Following chemical removal of tissue, the casts were further prepared for examination via scanning electron microscopy. By use of barium solution, microangiography was also performed on fixed tissue samples; the infused tissue was sectioned and imaged radiographically. Tissue samples were also collected for histologic evaluation after fixation and H&E staining. RESULTS The third compartment was supplied by 4 pairs of primary arteries and veins located around the circumference of the structure. From these vessels, smaller arteries and veins branched to supply the serosal surface and penetrated deeper through the tunica muscularis to supply the submucosal and mucosal layers. An extensive capillary network was arranged in a hexagonal array surrounding the gastric glands, such that the mucosal aspect of the replicas had a honeycomb-like appearance. Histologically, variably sized villous projections lined by a single layer of epithelial cells with an extensive glandular network were observed. CONCLUSIONS AND CLINICAL RELEVANCE The third compartment of the stomach of llamas is a highly vascular structure with an extensive anastomotic capillary network at the luminal surface. Branching vessels provide extensive collateral circulation, and it appears that surgical incisions should heal well. Incisions in the third compartment should be oriented parallel to the longitudinal plane.
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Affiliation(s)
- Linda M Van Hoogmoed
- Comparative Gastroenterology Laboratory, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
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10
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Chandranath SI, Bastaki SMA, Singh J. A comparative study on the activity of lansoprazole, omeprazole and PD-136450 on acidified ethanol- and indomethacin-induced gastric lesions in the rat. Clin Exp Pharmacol Physiol 2002; 29:173-80. [PMID: 11906479 DOI: 10.1046/j.1440-1681.2002.03626.x] [Citation(s) in RCA: 74] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
1. The proton pump inhibitors lansoprazole (LP) and omeprazole (OP) and the cholecystokinin (CCK)-receptor antagonist PD-136450 (PD) provide a broad spectrum of activities in their ability to inhibit gastric acid secretion and protect the stomach against ulcerogens. In the present study, we investigated the protective effects of these compounds against gastric ulcers induced by acidified ethanol (AE) and indomethacin. 2. Both AE (60% ethanol in 150 mmol/L HCl, 1 mL/rat) and indomethacin (30 mg/kg) produced gastric haemorrhagic lesions in the rat 1 and 6 h after oral administration, respectively. 3. The gastric mucosal protective effects of LP (1-20 mg/kg), OP (0.5-10 mg/kg) and PD (1-20 mg/kg), administered either orally or subcutaneously (s.c.) 30 min before the administration of AE or indomethacin, were dose dependent against both models of ulcer induction. 4. To determine whether the cytoprotective effect of LP, OP and PD (each 10 mg/kg) was mediated by endogenous prostaglandins (PG), indomethacin (10 mg/kg, s.c.) was administered 15 min before AE to inhibit prostanoids biosynthesis. Indomethacin reduced the cytoprotective effects of OP, but not LP, administered either orally or s.c. Indomethacin reduced the cytoprotective effect of PD administered orally, although the effect was much less significant than when PD was administered s.c. The results exclude the role of PG in mediating the protective effects of LP, whereas the possibility exists for PG to have a role in mediating the protective effects of OP and PD. 5. To investigate the possible involvement of endogenous nitric oxide (NO) in the cytoprotective action of LP, OP and PD, we treated rats with a selective inhibitor of NO synthesis, namely NG-nitro-L-arginine methyl ester (L-NAME; 25 mg/kg, s.c.). Administration of L-NAME 15 min prior to LP, OP or PD (each 10 mg/kg) orally or s.c. and challenge with AE or indomethacin did not significantly increase the degree of the ulcer index and L-NAME was not able to antagonize the protective effects of LP, OP and PD, thus excluding the role of NO in mediating the protective effects of these drugs. However, the effects of PD in reducing the indomethacin-induced ulcer index were less significant in the presence than the absence of L-NAME (P < 0.05 vs P < 0.001, respectively), suggesting a role for NO. 6. In conclusion, the results of the present study suggest that LP and OP are equally effective against AE- as well as indomethacin-induced gastric ulcers and were more potent than PD in protecting the stomach against ulcer formation. Lansoprazole, OP and PD bring about their cytoprotective action through the reduction of acid secretion and some other unknown mechanisms. However, OP and PD may exert their cytoprotective action through PG and NO pathways.
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Affiliation(s)
- S I Chandranath
- Department of Pharmacology, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
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11
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Christensen JM, Limsakun T, Smith BB, Hollingshead N, Huber M. Pharmacokinetics and pharmacodynamics of antiulcer agents in llama. J Vet Pharmacol Ther 2001; 24:23-33. [PMID: 11348484 DOI: 10.1046/j.1365-2885.2001.00302.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Plasma concentration time curves following intravenous (i.v.) administration of 1.5 mg/kg of ranitidine, 0.2 mg/kg, 0.4 mg/kg and 0.8 mg/kg of omeprazole, respectively, were analysed in six llamas. Plasma profiles after i.v. administration of both drugs showed plasma concentrations declining in a biexponential manner with a rapid distribution phase. Pharmacokinetics parameters after ranitidine administration to six llamas showed a mean elimination half-life of 1.53 +/- 0.26 h. The mean volume of distribution (Vdss) in llamas was 1.77 +/- 0.31 L/kg, and mean body clearance in llamas was 0.778 +/- 0.109 L/kg/h. Ranitidine produced only a small transitory (<1 h) decline in acid production when administered i.v. at a dose of 1.5 mg/kg. Omeprazole showed dose-dependent nonlinear pharmacokinetics. The mean half-life of 0.2 mg/kg i.v. omeprazole was shorter than that of 0.4 and 0.8 mg/kg i.v. omeprazole, i.e. 0.61, 0.72 and 1.07 h, respectively. The area under the curve (AUC) and mean residence time (MRT) increased with increasing dose, while clearance decreased as dose increased. The decline in acid production following 0.2 mg/kg i.v. omeprazole was highly variable and did not produce a clinically useful suppression of third compartment acid production. In contrast, both 0.4 mg/kg and 0.8 mg/kg omeprazole i.v. administration significantly reduced third compartment acid production. The reduction in acid production following 0.8 mg/kg omeprazole was not significantly greater than the reduction observed following 0.4 mg/kg dosage. Misoprostol (10 microg/kg) was administered i.v. in an absolute alcohol solution. Two animals collapsed following drug administration. While the side-effects could have been produced by either misoprostol or the alcohol vehicle, the clinical changes were more consistent with an adverse drug reaction. Unfortunately, the limitation of UV detection did not provide the sensitivity needed to quantify the amount of misoprostol in llama plasma, and the pharmacokinetics could not be evaluated.
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Affiliation(s)
- J M Christensen
- College of Pharmacy, Oregon State University, Corvallis, Oregon 97331-3507, USA
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12
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Pakodi F, Abdel-Salam OM, Debreceni A, Mózsik G. Helicobacter pylori. One bacterium and a broad spectrum of human disease! An overview. JOURNAL OF PHYSIOLOGY, PARIS 2000; 94:139-52. [PMID: 10791696 DOI: 10.1016/s0928-4257(00)00160-1] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Since the historical rediscovery of gastric spiral Helicobacter pylori in the gastric mucosa of patients with chronic gastritis by Warren and Marshall in 1983, peptic ulcer disease has been largely viewed as being of infectious aetiology. Indeed, there is a strong association between the presence of H. pylori and chronic active gastritis in histology. The bacterium can be isolated in not less than 70% of gastric and in over 90% of duodenal ulcer patients. Eradication of the organism has been associated with histologic improvement of gastritis, lower relapse rate and less risk of bleeding from duodenal ulcer. The bacterium possesses several virulence factors enabling it to survive the strong acid milieu inside the stomach and possibly damaging host tissues. The sequence of events by which the bacterium might cause gastric or duodenal ulcer is still not fully elucidated and Koch's postulates have never been fulfilled. In the majority of individuals, H. pylori infection is largely or entirely asymptomatic and there is no convincing data to suggest an increase in the prevalence of peptic ulcer disease among these subjects. An increasingly growing body of literature suggests an association between colonization by H. pylori in the stomach and a risk for developing gastric mucosa-associated lymphoid tissue (MALT), MALT lymphoma, gastric adenocarcinoma and even pancreatic adenocarcinoma. The bacterium has been implicated also in a number of extra-gastrointestinal disorders such as ischaemic heart disease, ischaemic cerebrovascular disease, atherosclerosis, and skin diseases such as rosacea, but a causal role for the bacterium is missing. Eradication of H. pylori thus seems to be a beneficial impact on human health. Various drug regimens are in use to eradicate H. pylori involving the administration of three or four drugs including bismuth compounds, metronidazole, clarithromycin, tetracyclines, amoxycillin, ranitidine, omeprazole for 1-2 weeks. The financial burden, side effects and emergence of drug resistant strains due to an increase in the use in antibiotics for H. pylori eradication therapy need further reconsideration.
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Affiliation(s)
- F Pakodi
- First Department of Medicine, Medical University of Pécs, Hungary
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13
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Abdel-Salam OM, Debreceni A, Mózsik G, Szolcsányi J. Capsaicin-sensitive afferent sensory nerves in modulating gastric mucosal defense against noxious agents. JOURNAL OF PHYSIOLOGY, PARIS 1999; 93:443-54. [PMID: 10674923 DOI: 10.1016/s0928-4257(99)00115-1] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
In the rat stomach, evidence has been provided that capsaicin-sensitive sensory nerves (CSSN) are involved in a local defense mechanism against gastric ulcer. In the present study capsaicin or resiniferatoxin (RTX), a more potent capsaicin analogue, was used to elucidate the role of these sensory nerves in gastric mucosal protection, mucosal permeability, gastric acid secretion and gastrointestinal blood flow in the rat. In the rat stomach and jejunum, intravenous RTX or topical capsaicin or RTX effected a pronounced and long-lasting enhancement of the microcirculation at these sites, measured by laser Doppler flowmetry technique. Introduction of capsaicin into the rat stomach in very low concentrations of ng-microg x mL(-1) range protected the gastric mucosa against damage produced by topical acidified aspirin, indomethacin, ethanol or 0.6 N HCl. Resiniferatoxin exhibited acute gastroprotective effect similar to that of capsaicin and exerted marked protective action on the exogenous HCl, or the secretagogue-induced enhancement of the indomethacin injury. The ulcer preventive effect of both agents was not prevented by atropine or cimetidine treatment. Capsaicin given into the stomach in higher desensitizing concentrations of 6.5 mM markedly enhanced the susceptibility of the gastric mucosa and invariably aggravated gastric mucosal damage evoked by later noxious challenge. Such high desensitizing concentrations of capsaicin, however, did not reduce the cytoprotective effect of prostacyclin (PGI2) or beta-carotene. Capsaicin or RTX had an additive protective effect to that of atropine or cimetidine. In rats pretreated with cysteamine to deplete tissue somatostatin, capsaicin protected against the indomethacin-induced mucosal injury. Gastric acid secretion of the pylorus-ligated rats was inhibited with capsaicin or RTX given in low non-desensitizing concentrations, with the inhibition being most marked in the first hour following pylorus-ligation. Low intragastric concentrations of RTX reduced gastric hydrogen ion back-diffusion evoked by topical acidified salicylates. It is concluded that the gastropotective effect of capsaicin-type agents involves primarily an enhancement of the microcirculation effected through local release of mediator peptides from the sensory nerve terminals. A reduction in gastric acidity may contribute to some degree in the gastric protective action of capsaicin-type agents. The vasodilator and gastroprotective effects of capsaicin-type agents do not depend on vagal efferents or sympathetic neurons, involve prostanoids, histaminergic or cholinergic pathways.
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Affiliation(s)
- O M Abdel-Salam
- First Department of Medicine, Medical University of Pécs, Hungary
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14
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Parkkila S, Parkkila AK. Carbonic anhydrase in the alimentary tract. Roles of the different isozymes and salivary factors in the maintenance of optimal conditions in the gastrointestinal canal. Scand J Gastroenterol 1996; 31:305-17. [PMID: 8726296 DOI: 10.3109/00365529609006403] [Citation(s) in RCA: 73] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- S Parkkila
- Laboratory of Oulu University Hospital, Finland
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15
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Kanemasa K, Okamura H, Kodama T, Ibata Y. Induction of VGF mRNA in neurons of the rat nucleus tractus solitarius and the dorsal motor nucleus of vagus in duodenal ulceration by cysteamine. BRAIN RESEARCH. MOLECULAR BRAIN RESEARCH 1995; 32:55-62. [PMID: 7494463 DOI: 10.1016/0169-328x(95)00059-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
To investigate the possible role of the brainstem in cysteamine-induced peptic ulceration, we examined the expression of VGF mRNA, which is induced in PC12 cells following application of nerve growth factor [23], in the nucleus tractus solitarius (NTS)/dorsal motor nucleus of vagus (DMV) complex of the medulla oblongata by in situ hybridization histochemistry. In control saline-treated rats, weak VGF mRNA signals were only rarely detected in neurons of the NTS and none were observed in those in the DMV. After 12 h of cysteamine administration (450 mg/kg, s.c.), the time at which duodenal ulcer was detected in all cases, heavily labeled VGF mRNA-expressing neurons appeared in the NTS and DMV. By quantitative analysis on macroautoradiogram, the VGF mRNA signals of the NTS/DMV complex in cysteamine-treated rats were twice as much as those in saline-treated rats. In situ hybridization histochemistry combined with the use of the retrograde neuronal tracer cholera toxin-B subunit revealed that the induced VGF mRNA-expressing neurons of the DMV projected directly to the stomach. The present results suggest that ulceration accompanies the induction of VGF mRNA in neurons of vagal afferent and efferent areas of the brainstem.
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Affiliation(s)
- K Kanemasa
- Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan
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16
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Abstract
Complications possibly related to battle injuries are not necessarily discovered immediately postwounding, but may surface many months or years later. Sometimes, the relationship is evident, but often it is difficult to prove the connection. Between 1975 to 1989, we treated 260 veteran wounded from Israel's wars (1948 to 1982). Of these, 122 patients suffered from abdominal complaints, and this study relates only to this group. Eighty percent of them had undergone surgery caused by abdominal trauma at the time of the original injury, and the remaining 20% were injured in areas other than the abdomen. Their complaints manifested several weeks to 35 years postinjury. Diagnosis was delayed for 1 to 8 years in 70% of the patients. Acute or chronic pain, dyspepsia, intolerance to certain foods, early satiety, nausea, vomiting, distension, disturbances in bowel movements, and discharge from unhealed wounds were the most frequently encountered complaints. After evaluation and diagnostic work-up, it was possible to establish diagnosis and afford appropriate treatment in 97 (77%) of the patients. Peptic ulcers were found in 31 patients; 10 required surgery for ulcer-related complications. Acute and repeated attacks of intestinal obstruction occurred in 19 patients; 14 required surgery. The cause of obstruction was adhesions in nine, and strictures, incarcerated hernias, and abscess formation in the rest. Ventral hernias at surgical, ostomy, and drain sites were found and repaired in 49 patients. Abdominal wall sinuses originating from foreign bodies or osteomyelitis were found in 13 patients, and low output enterocutaneous fistulas were found in three patients. Chronic abdominal abscesses were found in 15 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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Affiliation(s)
- J M Klausner
- Department of Surgery, Tel Aviv Sourasky Medical Center, Israel
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17
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Tarnawski A, Santos AM, Hanke S, Stachura J, Douglass TG, Sarfeh IJ. Quality of gastric ulcer healing. Is it influenced by antiulcer drugs? Scand J Gastroenterol 1995; 208:9-13. [PMID: 7777811 DOI: 10.3109/00365529509107755] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Chronic administration of sucralfate (SCR), a non-systemic ulcer-healing drug, exerts a trophic action on the gastric mucosa and prevents or reduces ulcer recurrence. The aim of this study was to determine whether SCR and/or the acid inhibiting drug omeprazole (OME) may affect the quality of ulcer healing, i.e., restoration of mucosal architecture. METHODS Gastric ulcers were produced in male rats by serosal application of acetic acid. Rats were gavaged twice daily for 14 days with 2 ml of: (a) Placebo (PLA), (b) SCR 500 mg/kg, or (c) OME, 50 mg/kg starting 48 h after ulcer induction. We determined ulcer size under a dissecting microscope, and performed quantitative histologic assessment of quality of healing score (QS) on a scale from 0 (normal) to 5 (most abnormal). RESULTS Ulcer size was 1.4 +/- 0.15 mm in the PLA group, 0.61 +/- 0.1 mm in the SCR group and 0.86 +/- 0.13 mm in the OME group (both OME and SCR p < 0.01 versus PLA). In the PLA group, histology showed (in rats with ulcers) a well-developed ulcer margin with cystically dilated glands. The QS of the ulcer scar in the PLA group was 3.3 +/- 0.22. IN the SCR-treated group, within the scar gastric glands were less dilated, more vertically oriented and the healing zone and granulation tissue were well developed and organized. The QS was 1.6 +/- 0.2, p < 0.001 versus PLA and OME. In the OME group, the ulcer margin and the scar were thinner-reduction of mucosal thickness by 43 +/- 2% (p < 0.005) and 18 +/- 1%, respectively, versus SCR and PLA groups. The number of dilated glands and connective tissue components in the scar was increased by 60%. The QS was 3.6 +/- 0.3. CONCLUSIONS (1) Both SCR and OME significantly reduced the size of the experimental gastric ulcer. (2) Restoration of mucosal architecture, assessed quantitatively, was much better in the SCR than in the OME and PLA-treated groups. (3) a trophic action of SCR on the gastric mucosa may be the basis of better quality of ulcer healing with SCR.
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Affiliation(s)
- A Tarnawski
- Dept. of Veterans Affairs Medical Center, Long Beach, CA 90822, USA
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18
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Tarnawski A, Tanoue K, Santos AM, Sarfeh IJ. Cellular and molecular mechanisms of gastric ulcer healing. Is the quality of mucosal scar affected by treatment? Scand J Gastroenterol 1995; 210:9-14. [PMID: 8578218 DOI: 10.3109/00365529509090261] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Ulcer healing, i.e. the reconstruction of the mucosal architecture, is an active process of filling the mucosal defect with proliferating and migrating epithelial cells and connective tissue. METHODS This article represents a summary of histologic and ultrastructural assessment of the cellular events occurring during healing of experimental gastric ulcer. RESULTS Mucosa adjacent to the ulcer crater forms a 'healing' zone. The gastric glands in this zone dilate and the epithelial cells lining these glands de-differentiate, express epidermal growth factor receptor, and proliferate. The latter is the result of local activation of genes encoding for EGF and its receptors. At the ulcer margin, proliferating and dividing epithelial cells migrate onto the granulation tissue to cover (re-epithelialize) the ulcer and bud into granulation tissue to reconstruct glandular structures within the ulcer scar. Re-epithelialization and reconstruction of epithelial structures is under control of epidermal growth factor (EGF) and related peptides which are produced locally by regenerating cells. Under control of fibroblast growth factors, granulation connective tissue grows extensively supplying (a) microvessels for restoration of the microvascular network and (b) connective tissue cells for restoration of the lamina propria within the mucosal scar. The final outcome of the healing process reflects a dynamic interaction between the epithelial component for the 'healing' zone at the ulcer margin and the connective tissue component (including microvessels) originating from the granulation tissue. Depending on these interactions, mucosal scar can be of good quality (restoration close to normal) or poor quality. While a number of pharmacologic agents affect gastric ulcer healing, it is unknown whether these drugs affect the quality of mucosal architecture reconstruction. In previous studies, we demonstrated that sucralfate exerts a trophic effect on gastric mucosa and, compared with omeprazole, improves the quality of restored mucosal structures within the scar of healed gastric ulcers. In the most recent studies, we demonstrated that treatment with sucralfate activates genes for EGF, bFGF, and their receptors, significantly increasing (vs placebo and omeprazole) expression of EGF and its receptor in ulcerated gastric mucosa. CONCLUSION Thus, the superior quality of ulcer healing by sucralfate (versus omeprazole) is most likely based on its capacity to induce and stimulate expression of EGF, bFGF, and their receptors.
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19
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Namiki T, Egawa M, Tominaga S, Inoue S, Takamura Y. Effects of GABA and L-glutamate on the gastric acid secretion and gastric defensive mechanisms in rat lateral hypothalamus. JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM 1993; 44:217-23. [PMID: 7901262 DOI: 10.1016/0165-1838(93)90034-r] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
The effects of administration of an inhibitory GABAergic or excitatory glutaminergic neurotransmitter into the lateral hypothalamic area (LHA) on gastric acids, an aggressive mechanism, and transepithelial potential difference (PD) and mucosal blood flow (MBF), defensive mechanisms, were examined in anesthetized rats, since lesions of LHA in these animals cause gastric mucosal damage and electrical stimulation stimulates gastric acids and antral contractions. Microinfusion of the inhibitory neurotransmitter, muscimol (GABA agonist) resulted in an increase in gastric acid secretion and in PD and MBF. The GABA antagonists picrotoxin and bicuculline methiodide, in contrast, decreased these three factors. The excitatory neurotransmitter L-glutamate induced only an increase of MBF. Thus, the GABAergic system in LHA stimulates the gastric functions, both defensive and aggressive mechanisms, while the glutaminergic system increases only a portion of the defensive system. The results suggest that there is a significant interaction between LHA and stomach functions.
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Affiliation(s)
- T Namiki
- Third Department of Internal Medicine, Yokohama City University, Medical School, Japan
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20
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Hernandez DE, Arandia D, Dehesa M. Rôle of psychosomatic factors in peptic ulcer disease. JOURNAL OF PHYSIOLOGY, PARIS 1993; 87:223-7. [PMID: 8136788 DOI: 10.1016/0928-4257(93)90009-i] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Evidence indicates that a link between peptic ulcer disease (PUD) and selected psychosomatic factors may exist. A series of 70 consecutive male and female adult patients were categorized by peptic symptoms and divided into four groups: a) controls; b) gastric ulcer (GU); c) duodenal ulcer (DU); and d) chronic non-ulcer dyspepsia (CNUD). All patients were interviewed and asked to answer a questionnaire that included demographics, medical history and the incidence of negative life events. A decreased level of activity was a predominant finding in GU, DU and CNUD patients. Family history of PUD may be correlated with CNUD. Of interest was the finding that DU and CNUD patients presented a higher incidence of negative life events when compared to the other study groups. Negative life events that produce considerable stress may predispose to peptic symptoms in certain patients.
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Affiliation(s)
- D E Hernandez
- Department of Medicine, Los Angeles County-University of Southern California School of Medicine 90033
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21
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Furr MO, Murray MJ, Ferguson DC. The effects of stress on gastric ulceration, T3, T4, reverse T3 and cortisol in neonatal foals. Equine Vet J 1992; 24:37-40. [PMID: 1555538 DOI: 10.1111/j.2042-3306.1992.tb02776.x] [Citation(s) in RCA: 46] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Sixteen neonatal foals stressed by disease underwent endoscopic examination of their stomachs and blood was assayed for triiodothyronine (T3), reverse T3 (rT3), thyroxine (T4) and cortisol, to determine the effects of severe physiological stress and the occurrence of gastric ulcers. compared with eight age-matched controls, six foals had abnormal cortisol, seven had abnormal T3 and 12 had abnormal T4. Eleven of 13 foals had rT3 outside the 95 per cent confidence interval for clinically normal foals of comparable ages. Gastric lesions were seen more frequently in stressed foals, and gastric glandular mucosal lesions were noted in 40 per cent of the stressed foals. Previous studies report low (3 per cent) occurrence of gastric mucosal lesions. The frequency of squamous mucosal lesions was not different from that reported previously, indicating that stress has little effect on the development of lesions at this site.
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Affiliation(s)
- M O Furr
- Marion du Pont Scott Equine Medical Center, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic and State University, Leesburg 22075
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22
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Mahgoub OM, Abdel-Hafeiz HB, Al-Quorain A, Al-Idrissi H, Al-Ghassab G, Absood G. Life events stress in Saudi peptic ulcer patients of the eastern province. Ann Saudi Med 1991; 11:669-74. [PMID: 17590822 DOI: 10.5144/0256-4947.1991.669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
The frequency of stress, as measured by the occurrence of 34 life events in the year preceding evaluation, was compared between 51 Saudis with peptic ulcers, diagnosed endoscopically, and 52 Saudis without peptic ulcer. All subjects were examined at King Fahd Hospital, Al-Khobar, Eastern Saudi Arabia, and were seen between March 1985 and July 1987. The mean number of events, their frequency distribution, and their categorization into areas of activity such as bereavement and other problems relating to health, marital, financial, and undesirable circumstances were similar for both groups. With regard to individual events, the only significant differences between ulcer patients and controls were that more patients had had serious arguments with in-laws or relatives and more controls had had minor personal illness or moderate financial problems. Excessive stress, as measured by life events, does not appear to be evident in Saudi peptic ulcer patients of the Eastern Province. Anxiety and/or depression was significantly more frequent in the group of patients with ulcers.
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Affiliation(s)
- O M Mahgoub
- Departments of Psychiatry, Internal Medicine, and Family and Community Medicine, College of Medicine, King Faisal University, Dammam, Saudi Arabia
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23
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Andersen LP, Holck S, Elsborg L, Justesen T. The Helicobacter (Campylobacter) pylori-colonized duodenal mucosa and gastric metaplasia. APMIS 1991; 99:244-8. [PMID: 2018637 DOI: 10.1111/j.1699-0463.1991.tb05145.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Biopsies were obtained from non-ulcerated sites of the duodenum from 100 dyspeptic patients. Helicobacter (Campylobacter) pylori was cultivated from 19 of these biopsies. Active chronic duodenitis (ACD) was found in 17 biopsies and more than 5% gastric metaplasia in 20 biopsies. H. pylori as well as ACD occurred with a significantly increased frequency when more than 5% gastric metaplasia was found in the duodenal biopsies. H. pylori on metaplastic tissue without ACD was, however, seen in two cases. H. pylori was cultivated from 9% and ACD was found in 5% of the biopsies with less than 5% gastric metaplasia. Gastric metaplasia in the duodenum was found significantly more frequently in patients with endoscopic duodenitis or duodenal ulceration than in patients with normal endoscopy. No association between gastric metaplasia in the duodenum and gastric pH or serum antibodies against H. pylori was seen. This study indicates that there is an established, but not exclusive, connection between gastric metaplasia and the colonization of the duodenum by H. pylori, the most important role being played by the antral gastric mucosa rather than the duodenum.
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Affiliation(s)
- L P Andersen
- Statens Seruminstitut, Dept. of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark
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24
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Affiliation(s)
- D E Hernandez
- Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033
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25
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Abstract
Clinical and laboratory evidence indicates that the brain exerts major control on the gastrointestinal tract. Specific brain loci and circuits that send efferent viscerotropic projections to the gut have been described. A variety of aminergic and peptidergic neurotransmitters have been shown to occur along these cerebrogastrointestinal pathways and to influence motor and secretory functions of the gut. Some of the newly identified peptides have been shown to influence the development of gastroduodenal ulcers. Findings with thyrotropin-releasing hormone (TRH) indicate that this endogenous tripeptide induces a full spectrum of gut effects, prominent among which is production of gastric ulcers. By contrast, other peptides including beta-endorphin, neurotensin, and bombesin induce gut effects opposite to those of TRH, namely, inhibition of gastric acid and motility and prevention of experimental ulcers. These laboratory findings suggest that ulcer disease may represent a brain-driven event, which may be the result of a neurochemical imbalance within the brain. Further neurobiological research will generate additional data on brain-gut interactions and will probably disclose new information to explain certain functional and organic disorders of the gut.
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Affiliation(s)
- D E Hernandez
- Department of Medicine, University of Southern California, School of Medicine, Los Angeles 90033
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26
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Gaska JA, Tietze KJ. Current concepts in the treatment of peptic ulcer disease: a case-oriented approach, Part 1. AMERICAN PHARMACY 1989; NS29:48-53. [PMID: 2683706 DOI: 10.1016/s0160-3450(15)31638-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
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27
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Abstract
Rats were divided into either an active group housed in activity wheels or a control group housed in stationary laboratory cages. Both active and control groups were further divided into groups receiving 1, 2, 3, or 4 meals daily for a total feeding time of 1 hr. Control rats were food-yoked to active animals. Results indicated that active rats fed 1 meal daily developed significantly more ulceration, lost more weight, and consumed less food and water than other groups. The number of daily meals had no effect on the amount of activity. No control animals developed ulcers, although they received the same amount of food. These results suggest that frequent feedings mitigate gastric peptic ulcer formation in rats placed in the activity-stress ulcer paradigm.
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Affiliation(s)
- K G Lambert
- Department of Psychology, Randolph-Macon College, Ashland, VA 23005
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28
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Abstract
An hypothesis involving a three step mechanism to account for the initiation of gastric lesions is described. The mechanism necessitates: (a) A drop in the internal energy (ATP) of the mucosal cells of the stomach upon being subjected to stress; either pathological or psychological. (b) Membranes of mucosal "suicidal sacs" containing potent lysosomal acid-hydrolases are rendered fragile and burst, thus releasing hydrolytic acid-hydrolases into the cytoplasm of the mucosal cells as the latter develop an energy deficit under stress. (c) Gastric mucosal cell necrosis, via the degradation of cytoplasmic and mucinous gastric glycoproteins by these lysosomal acid- hydrolases and subjection of the submucosal tissue to the corrosive effects of the luminal fluid containing hydrochloric acid and pepsin, i.e., initiation of gastric haemorrhage. The above mechanism is a general one that describes events associated with the development of gastric lesions regardless of the factor(s) or the agent(s) initiating gastric mucosal haemorrhage.
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Affiliation(s)
- F M Fouad
- Max-Planck Institut fur Biochemie, Martinsried bei Munchen, West Germany
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29
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Abstract
Dyspepsia associated with arthritis and non-steroidal anti-inflammatory drugs (NSAIDs) is a common clinical problem. Up to 80% of deaths attributable to peptic ulceration may be associated with NSAID usage. The problem is foremost in the elderly population, in which there has been an increase both in the incidence of peptic ulcers and in the use of NSAIDs. Although the development of duodenal ulceration is not clearly associated with NSAIDs, it is accepted that these drugs increase the risk of gastric ulceration and the occurrence of peptic ulcer complications. Asymptomatic peptic ulceration is common, and patients taking NSAIDs are often asymptomatic prior to presentation with life-threatening complications. The key principle in management of this problem is prevention through careful selection of patients for NSAID use, adequate treatment of peptic ulceration and maintenance of remission. A variety of effective drugs are available for the treatment of peptic ulcers, including H2-receptor antagonists, pirenzepine, sucralfate and colloidal bismuth subcitrate. However, it is recognised that peptic ulceration is a chronic disease with a relapsing-remitting course, often with asymptomatic ulcer episodes. The knowledge that current ulcer-healing strategies do not significantly alter this natural history has lead to increasing efforts to prevent relapse with effective 'maintenance' therapy.
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Affiliation(s)
- D Nunes
- Department of Clinical Medicine, Trinity College, Dublin, Ireland
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30
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Schubert TT, Frizzell JA, Meier PB, Cano RI, Schwartz KE. A US multicenter study of enprostil 35 micrograms twice daily for treatment of prepyloric, pyloric channel, and duodenal bulb ulcers. Enprostil Study Group. Dig Dis Sci 1989; 34:1355-60. [PMID: 2504566 DOI: 10.1007/bf01538068] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
One hundred twenty-seven patients with endoscopically diagnosed active duodenal, pyloric, or prepyloric ulcers participated in this multicenter, double-blind, randomized, controlled trial comparing placebo with enprostil 35 micrograms twice daily for up to four weeks. Cumulative endoscopic healing for the enprostil and placebo treatment groups, respectively, was 25% (15 of 59) and 12% (7 of 60) at two weeks (P = 0.060) and 59% (34 of 58) and 33% (19 of 57) at four weeks (P = 0.005). Excluding prepyloric ulcers, cumulative healing for the enprostil and placebo groups, respectively, was 22% (9 of 41) and 7% (3 of 44) at two weeks (P = 0.104) and 56% (23 of 41) and 24% (10 of 42) at four weeks (P = 0.002). A greater percentage of prepyloric ulcers healed on enprostil than placebo, but the difference was not significant. Mean antacid use in both groups was identical, averaging only two or less tablets per day in each group throughout the study. Daytime pain was relieved more quickly in the enprostil group, while median time to relief of nighttime pain was essentially identical in both groups. The most common side effect in the enprostil treatment group, diarrhea, was mostly mild to moderate in intensity and was generally self-limiting, requiring no specific therapy; no patient withdrew because of this complaint. Other symptoms and laboratory profiles were similar in the two groups. These results indicate that enprostil 35 micrograms taken twice daily for four weeks is effective and safe for the treatment of prepyloric, pyloric channel, and duodenal ulcers.
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Affiliation(s)
- T T Schubert
- Division of Gastroenterology, Henry Ford Hospital, Detroit, Michigan 48202
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31
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Hernandez DE, Walker CH, Valenzuela JE, Mason GA. Increased dopamine receptor binding in duodenal mucosa of duodenal ulcer patients. Dig Dis Sci 1989; 34:543-7. [PMID: 2702884 DOI: 10.1007/bf01536330] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
High-affinity and saturable membrane-bound dopamine binding sites have been characterized in rat and human gastrointestinal tissues. Although their role in experimental ulcerogenesis has been suggested, dopamine receptor activity in peptic ulcer disease has not been investigated. Radioligand binding studies were performed with mucosal tissue homogenates obtained from the antrum and duodenum of six male healthy volunteers and six male duodenal ulcer patients. The binding assay was performed in triplicate with a crude membrane fraction using [3H]dopamine as a ligand at a final concentration of 1 nM at 22 degrees C in the dark. Nonspecific binding (which usually comprised about 30% of total binding) was determined in the presence of a 100-fold excess of unlabeled dopamine. A significant (P less than 0.05) increase of [3H]dopamine binding was found in duodenal mucosa of duodenal ulcer patients. [3H]Dopamine binding in stomach (antrum) of normal and duodenal ulcer patients did not differ significantly. These findings provide preliminary evidence for a role of dopamine receptors in duodenal ulcer and suggest that biochemical abnormalities of gut dopamine function may be operative in the pathogenesis of peptic ulcer disease.
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Affiliation(s)
- D E Hernandez
- Department of Medicine University of Southern California, Los Angeles 90033
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32
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Szabo S, Spill WF, Rainsford KD. Non-steroidal anti-inflammatory drug-induced gastropathy. Mechanisms and management. MEDICAL TOXICOLOGY AND ADVERSE DRUG EXPERIENCE 1989; 4:77-94. [PMID: 2654544 DOI: 10.1007/bf03259905] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Affiliation(s)
- S Szabo
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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Meurman JH, Kuittinen T, Kangas M, Tuisku T. Buffering effect of antacids in the mouth--a new treatment of dental erosion? SCANDINAVIAN JOURNAL OF DENTAL RESEARCH 1988; 96:412-7. [PMID: 3201113 DOI: 10.1111/j.1600-0722.1988.tb01576.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Antacids are drugs of choice in the treatment of reflux esophagitis and peptic ulcer disease, where acid regurgitation may cause dental erosion. Since there are no specific preventive measures or effective treatment for erosions, the present study was made to assess whether the keeping of antacids in the mouth before swallowing would be beneficial with regard to their effect on mouth pH, after acidic challenge. Five healthy subjects formed the test panel. After measuring the acid binding capacity of all the antacid preparations in the Finnish market, the two most effective were selected for testing, one in emulsion form (Novaluzid), the other a tablet (Link). Acid regurgitation was mimicked by consuming a low-pH (3.2) drink immediately before the antacid. Control series were made with the acidic drink only. Both the antacids were found to counteract totally the pH fall caused by the drink, when measured as changes in the tongue surface pH. The Novaluzid preparation was more effective than the Link preparation but the difference was not significant. It may be anticipated that patients suffering from acid regurgitations would benefit if they are counseled to keep their antacids in the mouth for a while before swallowing.
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Affiliation(s)
- J H Meurman
- Department of Preventive Dentistry, Universities of Oulu, Finland
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Järvinen V, Meurman JH, Hyvärinen H, Rytömaa I, Murtomaa H. Dental erosion and upper gastrointestinal disorders. ORAL SURGERY, ORAL MEDICINE, AND ORAL PATHOLOGY 1988; 65:298-303. [PMID: 3162579 DOI: 10.1016/0030-4220(88)90113-2] [Citation(s) in RCA: 91] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
The orodental status, particularly dental erosions, of 109 patients with upper gastrointestinal symptoms was examined. In 44 patients, the underlying pathosis was associated with increased acid output in the stomach (reflux esophagitis or duodenal ulcer), while in 48 patients who underwent cholecystectomy, the duodenogastric reflux was alkaline. In 17 patients with gastric ulcer, the gastric secretion was usually normal. The diagnoses were made with gastroscopy. Seven patients with dental erosion were found, and they all came from the group of 35 dental patients with reflux esophagitis or duodenal ulcer. No erosions were seen in the other diagnostic groups (F = 0.02). Thus, gastrointestinal disorders with increased output of gastric acid may be linked with dental erosions. The finding emphasizes the need for accurate diagnosis and appropriate treatment of patients with upper gastrointestinal symptoms in order to avoid irreversible lesions in the teeth.
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Affiliation(s)
- V Järvinen
- Department of Cariology, University of Helsinki, Finland
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