Influence of a new antiulcer agent, ammonium 7-oxobicyclo (2, 2, 1) hept-5-ene-3-carbamoyl-2-carboxylate (KF-392) on gastric lesions and gastric mucosal barrier in rats.
Antiulcer effects of KF-392 were studied in several experimental gastric ulcer models in rats. It was found that KF-392 given orally at 1.0 to 5.0 mg/kg had a marked suppression on the developments of Shay ulcer as well as the aspirin-, stress-, and reserpine-induced gastric lesions. The influence of KF-392 on gastric mucosal barrier was also studied. A back diffusion of H+ into the gastric mucosa and a fall of transmucosal potential difference were induced with KF-392 given orally at the above mentioned doses. KF-392 given s.c. at 5.0 mg/kg showed no inhibition of Shay ulcer and no induction of back diffusion of H+ into the gastric mucosa. (+info)
The contribution of the swallowed fraction of an inhaled dose of salmeterol to it systemic effects.
Salmeterol is approximately eight times as potent as salbutamol for systemic effects. This may be because the drug is eight times more potent on receptors or there may be differences in systemic bioavailability. The systemic effects of salbutamol are limited by its fairly high first-pass metabolism, but the oral bioavailability of salmeterol is unknown. The contribution of the swallowed fraction of an inhaled dose of salmeterol to its systemic effects were analysed in a randomized, double-blind, crossover study. Twelve healthy subjects were given inhaled salmeterol 400 microg, inhaled salmeterol 400 microg plus oral activated charcoal or inhaled placebo plus oral activated charcoal on three separate days. Cardiac frequency (fC), Q-T interval corrected for heart rate (QTc), plasma potassium and glucose concentrations were measured for 4 h following the inhaled drug. Salmeterol with and without oral charcoal produced significant changes for all measures compared to placebo. The magnitude of effect following salmeterol alone was significantly greater than that following salmeterol plus charcoal for fC and glucose (mean (95% confidence interval) differences 8 (2-13) beats x min(-1), 0.59 (0.04, 1.13) mmol x L(-1), respectively) and nonsignificantly greater for QTc interval and potassium concentration. The differences between salmeterol given with and without charcoal suggest that 28-36% of the systemic response to salmeterol administered from a metered-dose inhaler are due to drug absorbed from the gastrointestinal tract. Thus, most of the systemic effects are due to the inhaled fraction of the drug. (+info)
Inhibition of protein denaturation by fatty acids, bile salts and other natural substances: a new hypothesis for the mechanism of action of fish oil in rheumatic diseases.
Natural hydrophobic substances like bile salts (cholate, deoxycholate, chenodeoxycholate, lithocholate and their conjugates with glycine and taurine), fatty acids (caprylic, capric, lauric, myristic, palmitic, stearic, oleic, linoleic, arachidonic, eicosapentaenoic and docosahexaenoic acid) were much more active (EC50 approximately 10(-4)-10(-5) M) than selected amino acids (EC50 > 10(-2) M) and inorganic salts (EC50 approximately 10(-1) M) in inhibiting heat-induced denaturation of human serum albumin in vitro. Fish oil, rich in n-3-polyunsaturated acids such as eicosapentaenoic acid and docosahexaenoic acid, administered p.o. (1 ml/kg) in the rat, protected ex vivo (after 2 hr) serum against heat-induced denaturation more than bendazac, a known antidenaturant drug. Thus, we speculated that the antidenaturant activity of fish oil may be partly (in addition to the known effect on endogenous eicosanoid composition) responsible for its beneficial effects in rheumatoid arthritis and other rheumatic conditions. In this connection, it is of note that the in vitro antidenaturant activity of fish oil fatty acids was higher than that of known antidenaturant drugs such as bendazac and bindarit and nonsteroidal anti-inflammatory drugs like phenylbutazone and indomethacin which could exert beneficial effects in chronic inflammatory conditions by stabilizing endogenous proteins. (+info)
Gastric decontamination--a view for the millennium.
The management of acute poisoning remains an important part of accident and emergency (A&E) care. Three gastric decontamination procedures have been widely used: gastric lavage, ipecac, and activated charcoal. Their role has recently been reviewed and position statements developed by working groups of the American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists. These have important implications for A&E, as they indicate that activated charcoal is now the agent of choice for most poisons, but than in most situations it is probably only effective if given within an hour of overdose. Ipecac is effectively obsolete and gastric lavage has a narrow range of indications, principally for potentially serious amounts of agents not adsorbed by charcoal. Protocols for care of overdose patients should be modified accordingly. (+info)
Noninvasive measurement of anatomic structure and intraluminal oxygenation in the gastrointestinal tract of living mice with spatial and spectral EPR imaging.
EPR imaging has emerged as an important tool for noninvasive three-dimensional (3D) spatial mapping of free radicals in biological tissues. Spectral-spatial EPR imaging enables mapping of the spectral information at each spatial position, and, from the observed line width, the localized tissue oxygenation can be mapped. We report the development of EPR imaging instrumentation enabling 3D spatial and spectral-spatial EPR imaging of small animals. This instrumentation, along with the use of a biocompatible charcoal oximetry-probe suspension, enabled 3D spatial imaging of the gastrointestinal (GI) tract, along with mapping of oxygenation in living mice. By using these techniques, the oxygen tension was mapped at different levels of the GI tract from the stomach to the rectum. The results clearly show the presence of a marked oxygen gradient from the proximal to the distal GI tract, which decreases after respiratory arrest. This technique for in vivo mapping of oxygenation is a promising method, enabling the noninvasive imaging of oxygen within the normal GI tract. This method should be useful in determining the alterations in oxygenation associated with disease. (+info)
Effect of brucine on mouse nonspecific immune responses.
AIM: To evaluate the effect of brucine (Bru) i.p. at analgesic doses on the nonspecific immune responses in normal and cyclophosphamide (Cyc)-treated mice. METHODS: The clearance of charcoal particles, the immune organ weights, the white blood cell counts in peripheral blood, the phagocytosis to neutral red (NR) of PMO and its IL-1 production in vitro were tested. RESULTS: In normal mice, Bru slightly enhanced the clearance of charcoal particles, the phagocytosis of PMO, IL-1 production, the immune organ weights and the WBC counts (P > 0.05), whereas in Cyc-induced subnormal immunity model mice, Bru greatly enhanced these nonspecific immune responses (P < 0.05 or P < 0.01). The effects of Bru were most marked i.p. at 10 mg.kg-1 in vivo or 0.1-10 mg.L-1 in vitro. CONCLUSION: Bru i.p. at an analgesic dosage has dose- and function-dependent immunoregulatory effects. (+info)
Evaluation of the buccal component of systemic absorption with inhaled fluticasone propionate.
BACKGROUND: Inhaled corticosteroids have dose related systemic effects determined by oral (swallowed or oropharyngeal absorption) and lung bioavailability. A study was undertaken to evaluate the significance of oropharyngeal absorption for fluticasone propionate. METHODS: Sixteen healthy volunteers of mean age 29.3 years were studied using an open randomised, placebo controlled, four way crossover design. Treatments were: (a) fluticasone metered dose inhaler (pMDI) 250 microg, 8 puffs; (b) fluticasone pMDI 250 microg, 8 puffs + mouth rinsing/gargling (water); (c) fluticasone pMDI 250 microg, 8 puffs + mouth rinsing/gargling (charcoal); and (d) placebo pMDI, 8 puffs + mouth rinsing/gargling (water). Overnight (ONUC) and early morning (EMUC) urinary cortisol/creatinine ratios and 8 am serum cortisol (SC) levels were measured. RESULTS: Significant (p<0. 05) suppression of ONUC, EMUC, and SC occurred with each active treatment compared with placebo. The mean values (95% CI for difference from placebo) were: (a) ONUC (nmol/mmol): fluticasone (2. 8, 95% CI 3.6 to 7.9), fluticasone + water (3.1, 95% CI 3.3 to 7.7), fluticasone + charcoal (2.3, 95% CI 4.1 to 8.5); placebo (8.6); (b) EMUC (nmol/mmol): fluticasone (5.6, 95% CI 8.4 to 24.5), fluticasone + water (7.6, 95% CI 6.6 to 22.4); fluticasone + charcoal (5.6, 95% CI 8.7 to 24.5); placebo (22.1). There were no significant differences between active treatments. The numbers of subjects with an overnight urinary cortisol of <20 nmol/10 hours were 0 (placebo), 11 (fluticasone), 12 (fluticasone + water), and 13 (fluticasone + charcoal). CONCLUSIONS: Oropharyngeal absorption of fluticasone does not significantly contribute to its overall systemic bioactivity as assessed by sensitive measures of adrenal suppression. In view of almost complete hepatic first pass inactivation with fluticasone, there is no rationale to employ mouth rinsing to reduce its systemic effects although it may be of value for reducing oral candidiasis. (+info)
Relative bioavailability of sodium cromoglycate to the lung following inhalation, using urinary excretion.
AIMS: To determine if a urinary excretion method, previously described for salbutamol, could also indicate the relative bioavailability of sodium cromoglycate to the lung following inhalation from a metered dose inhaler. Method Inhaled (INH), inhaled+oral charcoal (INHC), oral (ORAL) and oral+oral charcoal (ORALC) 20 mg doses of sodium cromoglycate were given via a randomised cross-over design to 11 healthy volunteers trained on how to use a metered dose inhaler. Urine samples were collected at 0.0, 0.5, 1.0 and up to 24 h post dosing and the sodium cromoglycate urinary concentration was measured using a high performance liquid chromatographic method. RESULTS: No sodium cromoglycate was detected in the urine up to 24 h following ORALC dosing. A mean (s.d.) of 3.6 (4.3) microg, 10.4 (10.9) microg and 83.7 (71.1) microg of the ORAL dose was excreted, in the urine, during the 0.5, 1.0 and 24 h post dose collection periods, respectively. Following INH dosing, the renal excretion was significantly higher (P<0.01) with 32.9 (14.5) microg, 61.2 (28.3) microg and 305.6 (82.3) microg excreted, respectively. The SCG excreted at 0.5, 1.0 and 24 h collection periods following INHC dosing were 26.3 (8.4) microg, 49.3 (18.1) microg and 184.9 (98.4) microg, respectively. There was no significant difference between the excretion rate of sodium cromoglycate following INHC when compared with INH dosing in the first 0.5 and 1.0 h. CONCLUSIONS: The urinary excretion of sodium cromoglycate in the first 0.5 h post inhalation can be used to compare the relative lung deposition of two inhaled products or of the same product using different inhalation techniques. This represents the relative bioavailability of sodium cromoglycate to the lung following inhalation. Similar 24 h urinary excretion of sodium cromoglycate can be use to compare the total dose delivered to the body from two different inhalation products/inhalation methods. This represents the relative bioavailability of sodium cromoglycate to the body following inhalation. Because of the lack of difference between the INH and INHC in the first 0.5 h, the use of activated charcoal is not necessary when this method is used to compare the relative lung bioavailability of different products or techniques. (+info)