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PubMed2003

Proteinase-activated receptor-2: physiological and pathophysiological roles.

Protease-activated receptor 2 (PAR2) is the second member of a new subfamily of G-protein coupled receptors: the protease-activated receptors (PARs). At present, four different PARs have been cloned and all of them share the same basic mechanism of activation. A serine protease cleaves the extended, extracellular N-terminus of the receptor at a specific site within the protein chain to expose an N-terminal tethered ligand domain, which binds to and activates the cleaved receptor. In this manner, trypsin and mast cell beta-tryptase activate PAR2. PARs are single use receptors because proteolytic activation is irreversible and the cleaved receptors are degraded in lysosomes. Thus, PARs play important roles in emergency situations, such as trauma and inflammation. Emerging evidence indicates that PAR2 is involved in the cardiovascular, pulmonary and gastrointestinal systems, where it controls inflammation and nociception. Work with selective agonists and knockout animals suggests a contribution of PAR2 to certain inflammatory diseases. Therefore, selective antagonists or agonists of these receptors may be useful therapeutic agents for the treatment of human diseases.

Animals↗

PubMed1999

[Cutaneous polyarteritis nodosa associated with streptococcal infection in a child and a review of the literature].

Polyarteritis nodosa (PAN) is a multisystem inflammatory disease associated with necrosis of small and medium arteries. It can occur in a systemic form with manifestations in skin, joints, heart, nervous system, gastrointestinal tracts, lungs and kidneys. It is relatively rare in adults and even more in children. It may be divided into a cutaneous form (C-PAN) and a more generalized form (G-PAN). Usually C-PAN is thought to run a benign course. But some cases were reported to run chronic courses and be diagnosed G-PAN. It has been reported that some adults with PAN are related to HBV infection. On the other hand most children with PAN had upper respiratory infections some with streptococcal infections. We described a 5-year-old boy who was suffering from high fever, joint pain, subcutaneous nodular and livedo reticularis. We diagnosed him C-PAN by examination and clinical course. Anti-streptolysin O (ASO) and anti-streptokinase (ASK) increased and we suspected that C-PAN followed after streptococcal infection. We reviewed the literatures of C-PAN and streptococcal infection in childhood. Streptococcal infection has been implicated by a positive throat swab or an increase in ASO. There were 25 cases (75.7%) which were thought to be related with prior streptococcal infection in 33 cases. We thought that C-PAN may be associated with streptcoccal infection in childhood.

Child, Preschool↗

PubMed1989

Prevalence of alcohol related admissions to general medical units.

The prevalence of alcohol related admissions to hospitals in Manitoba was examined in an investigation limited to the general medicine units of four representative hospitals within the province. All admissions during one-month periods were closely examined. In order to determine if an admission was related to alcohol, the investigators obtained permission from each patient to ask the attending physician to rate the degree to which they felt the admission was alcohol related, and intensively reviewed all charts. The percentage of alcohol related admissions was found to range from 6.38 percent to 14.93 percent on medical units. The disorders which alcohol related patients presented on admission tended to differ from those in the not-related category. At all hospitals, disorders of the gastrointestinal system were in the majority for the alcohol related group, while the not-related group presented more difficulty in the area of cardiovascular disorders. The cost which is associated with these alcohol related admissions is large, the highest being $61,050.00 for a one-month period in one of the hospitals surveyed. The findings clearly indicate that in Manitoba, health care facilities and health care professionals are very much involved in problems related to alcohol. The findings of this study indicate that the problem is with us and we should make every effort to ensure proper and effective care, and to establish systems for the identification and referral of alcohol related admissions.

Adult↗

PubMed1988

Gut peptide-mediated adaptive response of the exocrine pancreas.

The gastrointestinal system is substantially involved in the regulation of exocrine pancreatic secretion, and it is therefore not surprising that intestinal diseases have been shown to affect exocrine pancreatic function. In rat experiments gastrectomy, truncal vagotomy, and subtotal colectomy stimulated pancreatic growth and altered pancreatic enzyme composition. Focusing on two main hormones supposed to be involved in the regulation of pancreatic adaptation, we studied basal and stimulated gastrin and cholecystokinin (CCK) pattern after the operative procedures. After total gastrectomy basal CCK values were unchanged, whereas postprandial CCK plasma values and the integrated postprandial CCK release were significantly increased. After subtotal colectomy CCK levels, both basal and postprandial, were significantly increased. In both of these conditions gastrin levels were either decreased (total gastrectomy) or unchanged (subtotal colectomy). CCK may therefore be the major humoral candidate to promote the observed pancreatic adaptive response. After truncal vagotomy CCK values remained unchanged, whereas basal and postprandial gastrin was significantly increased. Gastrin may be a candidate involved in the stimulation of pancreatic trophism after vagisection.

Adaptation, Physiological↗

PubMed1989

Side effects of anti-ulcer prostaglandins: an overview of the worldwide clinical experience.

Anti-ulcer prostaglandins (PG)--misoprostol, enprostil and rioprostil--have been given to more than 5000 patients in short-term studies on gastric and duodenal ulcer. Analysis of these studies shows the drugs to be safe. Their side effects appear to be dose-dependent and mainly restricted to the gastrointestinal system, the major syndromes being diarrhoea and abdominal pain. The clinical relevance of PG-related unwanted effects, though in average exceeding that of H2-blockers, seems to be sufficiently low. In terms of safety efficacy, however, they appear inferior to H2-antagonists, so their routine use in preference to the latter compounds is still premature.

Alprostadil↗

PubMed1995

Nitric oxide-based possibilities for pharmacotherapy.

The goal of nitric oxide (NO) based pharmacotherapy is to reach proper homeostasis of NO metabolism in the target tissue where endogenous production of NO is either too weak or excessively increased. In addition to the classic NO-based therapy of cardiovascular conditions with nitrates, a variety of new therapeutic possibilities have emerged including sexual disorders, gastrointestinal system, immunology, tumour growth regulation and respiratory disorders. NO levels of target tissues can be affected directly by NO donors, or indirectly by increasing the level of L-arginine, a substrate of nitric oxide synthase (NOS). While increased production of NO by induceable NO (iNOS) by, for example, cytokines does not at present seem therapeutically meaningful, increased NO production by constitutive NOS (cNOS) may be involved in the beneficial effects of ACE inhibitors or oestrogens. NO production may be pharmacologically decreased by inhibition of expression of iNOS by glucocorticoids while both cNOS and iNOS derived NO production is inhibited by administration of false substrates, for example L-NAME. Additionally, the respiratory system and related vessels can be reached directly and more selectively by inhalation of pure NO gas. Possible problems in administering NO and perhaps some NO-donors include the toxic nature of the compound itself whereby vital enzyme systems may be inhibited and tissue damaging radicals formed. Future prospects of NO-based pharmacotherapy may feature selective ligands to different NOS isoforms and tissue selective donors that release NO in a controlled fashion.

Adult↗

PubMed1995

Erythropoiesis and erythropoietin in multiple myeloma.

In this review, the pathophysiology and treatment of the anemia of multiple myeloma will be examined. While the anemia of cancer has multiple causes, an important component is labeled the "anemia of chronic disease" which is characterized by the combination of a shortened erythrocyte survival with failure of the bone marrow to increase red cell production in compensation. Depressed erythropoiesis is itself related to a combination of factors, including impaired availability of storage iron, inadequate erythropoietin response to anemia, and overproduction of cytokines which are capable of inhibiting erythropoiesis. These cytokines are involved in the retention of iron in the reticuloendothelial system, gastrointestinal tract and hepatocytes, may interfere with erythropoietin production by the kidney, and may exert direct inhibitory effects on erythroid precursors. While overproduction of several such cytokines, including IL-6, IL-1 and TNF-alpha, has been definitely demonstrated in multiple myeloma patients, it is still unclear whether they are directly involved in the pathogenesis of the anemia which develops. Although several mechanisms, such as hemodilution, bleeding, and decreased red cell survival operate, the anemia is mostly caused by defective erythropoietic activity. This in turn is partly explained by inadequate erythropoietin (Epo) production even in some patients without renal impairment. Based on measurements of serum erythropoietin and transferrin receptor, the distinction between marrow unresponsiveness to normal Epo stimulation and deficient Epo production is important for the treatment of the anemia of multiple myeloma with recombinant human Epo. Higher doses would probably be necessary if adequate Epo production is present, whereas only replacement therapy with lower doses may be sufficient when Epo production has been shown to be inappropriate.

Anemia↗

PubMed1995

Severity grading of childhood poisoning: the Multicentre Study of Poisoning in Children (MSPC) score.

Scores for severity grading of childhood poisoning may be useful in comparing different causes of poisoning, in order to identify the main risks and their changes over time. The Multicentre Study of Poisoning in Children score is based on four levels of severity (1-mild, 2-moderate, 3-severe, 4-very severe) involving nine target groups: seven relating to organ systems (gastrointestinal, nervous, respiratory, circulatory, renal, hepatic, skin), one to metabolic abnormalities and one to injuries from corrosive substances. Each patient is classified by the highest level attributed to any one of the nine groups. The score has been prospectively tested in 644 symptomatic children, aged 0-13 years, admitted to six pediatric hospitals of Northern Italy from January 1, 1991 to December 31, 1993. Poisoning was categorized as mild (1) in 357 children (53.8%), moderate (2) in 285 (42.9%), severe (3) in 18 (2.7%) and very severe (4) in 4 (0.6%). No deaths occurred. Severity grading according to The Multicentre Study of Poisoning in Children score confirms the prevalence of mild and moderate poisonings in children; the score seems to be an objective method suitable for epidemiological studies in different countries. Its clinical usefulness deserves more investigation.

Adolescent↗

PubMed2005

Comparison of Helicobacter spp. genetic sequences in wild and captive seals, and gulls.

Helicobacter species are widely distributed in the gastrointestinal system of humans and many animal taxa. Investigations of natural infections are essential to elucidating their role within the host. The feces of fur seals Arctocephalus pusillus doriferus and sea lions Neophoca cinerea from 3 separate captive populations, as well as a wild colony from Kangaroo Island, Australia, were examined for the occurrence of Helicobacter spp. The feces from several wild silver gulls Larus novahollandiae were also investigated. As detected by PCR, 18 of 21 samples from captive and 12 of 16 samples from wild seals were positive for Helicobacter spp. Three species were identified in these animals. Whilst one possibly novel type was identified from wild fur seals, the majority of wild and captive individuals had the same species. This species also occurred in more than 1 seal type and in silver gulls, and shared a 98.1 to 100% identity to other Helicobacter spp. from harp seals and sea otters. A similar sequence type to species identified from cetaceans was also detected in several captive seals. This study reports for the first time the presence of Helicobacter spp. in wild and captive seals and demonstrates the diversity and broad-host range of these organisms in the marine host.

Animals↗

PubMed1988

Absorption of 14C-2-hydroxy-4-(methylthio)butanoic acid (Alimet) from the hindgut of the broiler chick.

The purpose of these studies was to examine the role of the hindgut of the broiler chick in the absorption of 2-hydroxy-4-(methylthio)butanoic acid (HMB). When 14C-HMB was delivered directly into the hindgut, the rate of absorption from this gastrointestinal site was about 40% of the administered dose per hour. Plasma radiolabel appearance indicated that the 14C-HMB lost from the hindgut was being absorbed into the bloodstream of the bird. Decarboxylation experiments using cecal microorganisms showed that the loss of 14C-HMB could not be accounted for by bacterial metabolism. When birds were dosed with radiolabelled HMB and tissue samples were tested, results showed that the 14C-HMB that was absorbed from the hindgut was incorporated into protein in a dose-related manner. In addition, an equimolar, equal specific activity intraperitoneal dose of HMB did not alter the rate of HMB adsorption from the hindgut. This indicates that HMB absorption from the gut is not limited by HMB already in the body tissues. This result confirmed that the rate of HMB diffusion into the blood and its conversion to methionine in body tissues were sufficient to maintain the concentration gradient required for the continued absorption of HMB. Finally, whole body autoradiography comparing 35S-HMB and 35S-DL-methionine showed no substantial differences in terms of label density or distribution. These studies demonstrate that 14C-HMB disappears from the lumen of the large intestine and ceca when it is administered directly into the hindgut. This research confirms that HMB is absorbed throughout the entire gastrointestinal system.

Animals↗

PubMed2005

Soluble adhesion molecules ICAM-1, VCAM-1, P-selectin in children with Helicobacter pylori infection.

AIM: To assess the sICAM-1, sVCAM-1, and sP-selectin levels in children with Helicobacter pylori (H pylori) infection and to evaluate their significance for the morphological changes found in gastric mucosa. METHODS: The study included 106 children: 59 children (55.7%) with chronic gastritis and positive IgG against H pylori, 29 children (27.3%) after previous H pylori infection without the bacterium colonization but with positive IgG against H pylori, and 18 children (17%) with functional disorders of the gastrointestinal system but with normal IgG against H pylori. Endoscopic and histopathological evaluation of gastric mucosa was performed based on the Sydney System classification. The evaluation of sP-selectin, sICAM-1, sVCAM-1 levels in the sera of children was carried out using ELISA test. RESULTS: The assessment of gastritis activity degrees indicated statistically significant values in the antrum and corpus (P<0.001) of children examined. Serum sVCAM-1 levels were higher in group with gastritis due to H pylori infection than in group without infection and differed statistically (P<0.05). Serum sVCAM-1 levels proved to be the highest among other adhesive molecules in infected children and decreased after eradication of H pylori. Serum sICAM-1 levels were similar in all examined groups. Serum sP-selectin levels were similar in children with and without H pylori infection. CONCLUSION: Assessment of adhesive molecules (sP-selectin, sICAM-1, sVCAM-1) in the sera of children with active H pylori infection can show the participation of sVCAM-1 in the pathogenesis of gastric mucosal inflammation. sP-selectin and sICAM-1 concentrations in the sera of children with H pylori infection after eradication cannot reveal any significant differences as compared to healthy children.

Adolescent↗

PubMed2006

Apoptosis in skeletal muscle and its relevance to atrophy.

Apoptosis is necessary for maintaining the integrity of proliferative tissues, such as epithelial cells of the gastrointestinal system. The role of apoptosis in post mitotic tissues, such as skeletal muscle, is less well defined. Apoptosis during muscle atrophy occurs in both myonuclei and other muscle cell types. Apoptosis of myonuclei likely contributes to the loss of muscle mass, but the mechanisms underlying this process are largely unknown. Caspase-dependent as well as -independent pathways have been implicated and the mode by which atrophy is induced likely determines the apoptotic mechanisms that are utilized. It remains to be determined whether a decrease in apoptosis will alleviate atrophy and distinct research strategies may be required for different causes of skeletal muscle loss.

Animals↗

PubMedDate not supplied

Congestive heart failure due to a pancreatic pseudocyst.

BACKGROUND: Mediastinal extension of pancreatic pseudocysts has caused rare cases of cardiac compression, but to our knowledge, congestive heart disease due to cardiac compression by a pancreatic pseudocyst has never been reported. SUMMARY: A 48-year-old man presented with dyspnea, swelling of both lower limbs, left-sided chest pain, and colicky, nonradiating epigastric pain. Computed tomography of the abdomen and lower thorax revealed a huge cystic mass directly behind the heart, extending through the esophageal hiatus into the abdomen. The patient subsequently noted dysphagia and epigastric pain and began vomiting after meals. Radiography of the upper gastrointestinal system with barium contrast confirmed that the lower end of the esophagus and the right and lower portions of the stomach were extrinsically compressed. Complete recovery followed surgical removal and internal drainage of a large pancreatic pseudocyst. CONCLUSIONS: Mediastinal extension of a pancreatic pseudocyst can cause cardiac compression, leading to congestive heart failure.

Heart Failure↗

PubMed2006

[Lithium intoxication].

Lithium intoxication has a low prevalence, the 75% of patients with treatment with lithium could have toxic levels of lithium during the treatment. Asymptomatic patients have been observed with doses under 2.5 mmol/L. Systems with high prevalence of symptoms are the nervous system, gastrointestinal tube and cardiovascular. Symptoms could appear from two hours to four hours after ingestion. Early hours after lithium ingestion, levels of lithium are not related with severity. However, monitoring seric levels is necessary to lead therapeutic approach and to give a prognosis. Induce urine with isotonic solution, is used during therapeutic approach. Other therapeutic option is dialysis. In summary, intoxication with lithium could be a severe situation. It is necessary to describe therapeutic protocols in this entity.

Drug-Related Side Effects and Adverse Reactions↗

PubMed1981

Hazards of heat exposure. A review.

The usefulness of the various heat stress standards recommended by occupational health authorities in the United States is discussed from the point of view of their effectiveness in preventing acute heat illnesses. In this connection, the findings from an investigation of four recent fatal industries heat casualties are described. A review is presented of the recent literature on acute occupational heat illnesses. Also reviewed is the information on chronic heat illnesses. Most of this latter data comes from studies performed in Europe and South America. However, a recent mortality study among steel workers in the United States contributed significantly to the knowledge of this problem area. This study found the primary targets of chronic heat illnesses to the cardiovascular and the gastrointestinal systems, although there was some evidence that the reproductive functions may be affected. A discussion on how to prevent heat illnesses is presented.

Acute Disease↗

PubMedDate not supplied

Management and complications following trigonal-colonic anastomosis in a dog: five-year evaluation.

Urinary diversion procedures in the dog have been described for both benign and malignant processes involving the bladder, urethra, or both. These procedures are performed rather infrequently, primarily because of the potential complications associated with urinary diversion into an intact gastrointestinal system. A case managed for five years following trigonal-colonic anastomosis for lymphocytic-plasmacytic urethritis is presented, along with a review of urinary diversion techniques. Postoperative management recommendations following urinary diversion are discussed.

Anastomosis, Surgical↗

PubMed1985

Tocainide: a new oral antiarrhythmic agent.

Tocainide, a newly released class 1B antiarrhythmic agent, has membrane stabilizing and electrophysiologic characteristics similar to those of lidocaine, but it can be prescribed for oral administration. Investigational studies in both animals and humans have shown tocainide's effectiveness for the treatment of ventricular arrhythmias in chronic and acute settings. The drug has nearly 100% bioavailability after oral administration and an effective half-life of 9 to 37 hours (mean, 15 hours). Antiarrhythmic efficacy is similar to that of other class I medications currently in use. Serious side effects most frequently involve the central nervous or gastrointestinal system and occur in 10% to 20% of patients. Tocainide has minimal negative inotropic effects and a tendency to shorten effective refractory periods.

Administration, Oral↗

PubMed1997

Safety of oral terbinafine for toenail onychomycosis.

This open-label multicenter study evaluated the safety and efficacy of 12, 18, and 24 weeks of daily treatment with a 250-mg tablet of terbinafine for onychomycosis of the toenails. The safety data for 1,508 patients with a mean age of 50 years are reported here. Percentages below are based on this denominator. All patients received at least 12 weeks of therapy, with a possible addition of 6 or 12 weeks depending on disease extent. Patients were evaluated at baseline and at weeks 6, 12, 24, 30, 36, 48, and 72. Adverse events were reported in 674 (44.7%) patients; the events were considered unrelated to terbinafine in 557 (36.9%) patients and causally related or of uncertain relationship to terbinafine in 117 (7.8%) patients. Most events involved the skin, the gastrointestinal system, or the respiratory system. Statistically similar results were found for the elderly (over 60 years) and diabetic subpopulations. The study results confirm the safety of terbinafine in the population at large and show no differences for either the elderly or diabetic patients, who are at increased risk for onychomycosis and who frequently take concomitant medications with potential for drug interactions.

Antifungal Agents↗