Gastrointestinal blood loss after non‐steroidal anti‐inflammatory drugs. Measurement by selective determination of faecal porphyrins.

Abstract

1. A method for the detection of gastrointestinal blood loss based upon the selective measurement of faecal porphyrins was tested in two studies in healthy volunteers. 2. In the first study subjects (n = 6) received intragastric autologous blood (saline, 2 and 6 ml as a single dose) resulting in a dose dependent increase in faecal porphyrins. 3. In a subsequent placebo controlled cross over study in 12 subjects acetylsalicylic acid (ASA), nabumetone (a new NSAID) or placebo were administered for 5 days with a washout period of 9 days. They were no dietary restrictions. 4. All faeces were collected during the treatment period and both the full faecal homogenate and a random faecal sample were analyzed for deutero‐ and pemptoporphyrin content by h.p.l.c. Additionally a benzidine reaction was performed. 5. There was a highly significant correlation (r = 0.95) between the values obtained from random samples and the full homogenate. ASA increased the faecal porphyrin excretion (P less than 0.001) compared with placebo in contrast to nabumetone. Complaints of dyspepsia were most common after ASA. 6. Measurement of faecal porphyrins is useful for monitoring NSAID induced upper gastrointestinal blood loss and lacks some of the practical constraints of other methods.

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“…The effect of aspirin on faecal porphyrins is in agreement with the previous work of Cohen et al [5] who have shown that 800 mg aspirin given thrice daily for 5 days produced significant increases in pemptoporphyrin and deuteroporphyrin, compared with placebo. These porphyrins result from the breakdown of protoporphyrin, which itself is the product of haemoglobin degradation in the faeces.…”

“…These porphyrins result from the breakdown of protoporphyrin, which itself is the product of haemoglobin degradation in the faeces. This latter observation is in contrast to Cohen et al [5] who showed no change or a trend for a decrease in porphyrins with time in the placebo group. After 5 days of dosing with aspirin in the current study, protoporphyrin was the only porphyrin that was significantly elevated compared with placebo.…”

“…Faecal porphyrins were measured by collecting faecal samples on each trial day and assaying for the relative dry weight concentrations of protoporphyrin, deuteroporphyrin, pemptoporphyrin and coproporphyrin 1 as detailed in the method of Cohen et al [5]. The porphyrin concentrations calculated for each sample were grouped within each trial day.…”

“…To assess the influence of NSAIDs on gastrointestinal mucosal integrity, measurement of gastrointestinal blood loss using faecal porphyrins has been shown to provide a reliable marker [5]. These workers have demonstrated that dosing with aspirin leads to a significant increase in porphyrins appearing in faecal samples after five days of dosing.…”

Role of Protein Kinase Network in Excitation-Contraction Coupling in Smooth Muscle Cell

“…One of the most important intracellular acceptors of the Ca 2+ signal is calmodulin (CaM), which exerts a modulating influence on the function of Ca 2+ /CaM-dependent protein kinases. Among them, the CaMKII shows a broad substrate specificity and has been thought to be a multifunctional protein kinase (Cohen et al, 1992;Colbran et al, 1989a;Colbran et al, 1989b). Four genes encode related but distinct isoforms of CaM kinase II ( , , , and ).…”