Importance of local versus systemic effects of non-steroidal anti-inflammatory drugs in increasing small intestinal permeability in man

Article Abstract:

Nonsteroidal anti-inflammatory drugs (NSAIDs) are often prescribed in cases of chronic inflammation, such as rheumatoid arthritis. Gastrointestinal side effects, including bleeding, inflammation, protein loss, and anatomical abnormalities, frequently accompany NSAID administration. NSAIDs cause these effects by direct action on the gastrointestinal mucosa during absorption, during exposure to the intestines while circulating in the bloodstream, and when they are reintroduced into the intestines with secreted bile, but the relative importance of these three types of exposure is not known. The drug nabumetone is an NSAID precursor that is converted into its active NSAID metabolite (6-methoxy-2-napthylacetic acid) in the systemic circulation, and is not appreciably incorporated into bile by the liver. Hence, its only opportunity to act on the gastrointestinal mucosa would be during circulation in the systemic blood. To evaluate the importance of NSAID concentrations in the systemic circulation, the effects of nabumetone were compared with the effects of indomethacin (a commonly prescribed NSAID with significant side effects) in 12 healthy volunteers. After one week of treatment with either nabumetone or indomethacin, there were no changes in the absorption of a variety of carbohydrates. The permeation of radioactively labeled EDTA was significantly increased in patients receiving indomethacin, but not nabumetone. (EDTA absorption is an index of nonspecific intestinal permeability; enhanced permeability is one of the steps in the development of gastrointestinal pathology.) Inasmuch as bumetanone, which had no effect on permeability, is only active in the systemic circulation, exposure of the gastrointestinal mucosa to NSAIDs would not appear to occur at this level, and the critical exposure more likely occurs during drug absorption or biliary excretion. (Consumer Summary produced by Reliance Medical Information, Inc.)

Complications and side effects, Nonsteroidal anti-inflammatory drugs, Nonsteroidal anti-inflammatory agents, Intestinal absorption, Intestine, Small, Small intestine

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A current view of the type II syndrome: age of onset, intellectual impairment, and the meaning of structural changes in the brain

Article Abstract:

The positive, or type I, syndrome in schizophrenia is marked by florid symptoms, including delusions, hallucinations and incoherent speech. The negative, or type II, syndrome is usually defined by social withdrawal, flat emotions and poverty of speech. Three studies evaluated structural brain changes in chronic schizophrenia, ways in which antipsychotic (neuroleptic) medications affect different psychotic symptoms, and schizophrenia-related neuronal (nerve cell) changes. Study findings were evaluated in terms of clarifying or further distinguishing the two-syndrome concept of schizophrenia. Computer tomography (CT) scans demonstrated that patients with negative or deficit symptoms have more reductions of chemicals known as neuropeptides in the limbic portions of their brains than patients with primarily positive symptoms. Patients with negative symptoms were also found to have reduced monoamine oxidase type B activity. Increases in the size of the brain ventricles were found to be related to behavioral deterioration and to dyskinesia (voluntary movement disorders), but were not related to either negative symptoms or intellectual impairment. The negative syndrome was also found to be relatively nonresponsive to neuroleptic (antipsychotic) medication and highly related to illness chronicity, behavioral deterioration and dyskinesia. However, negative symptoms that occurred in conjunction with positive symptoms often did respond to neuroleptics. It is concluded that negative symptoms should be divided into primary and secondary types. For example, social withdrawal can either be a primary symptom or a secondary response to a delusion or hallucination. Early illness onset was found to be highly related to the development of negative symptoms and illness chronicity and deterioration were found to be related to progressive brain abnormalities. (Consumer Summary produced by Reliance Medical Information, Inc.)

Psychological aspects, Identification and classification, Cognition, Emotions, Dopaminergic mechanisms, Emotions and cognition

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Small intestine permeability in schizophrenia

Article Abstract:

The theory that intestinal permeability (IP) is abnormal in schizophrenic patients was studied by comparing 24 schizophrenic patients with 43 healthy comparison subjects (controls). Twelve of the patients were in relapse and 12 were in remission. Nineteen patients had celiac disorder (an abdominal sensitivity to gluten, a cereal-grain protein). Almost all the patients were taking neuroleptic (antipsychotic) drugs and some were also taking antidepressant medications. Since alcohol and non-steroidal anti-inflammatory drugs (NSAIDs; e.g., aspirin) have been shown to increase IP, none of the patients or controls had ingested alcohol during the week before testing or had taken NSAIDs for three weeks prior to testing. IP was assessed by having patients and controls fast overnight then drink a solution of radioactively labelled edetic acid (EDTA) diluted with water. Two hours later, normal eating and drinking were resumed and urine was collected and evaluated for EDTA excretion over a 24-hour period. No EDTA excretion differences were found between schizophrenic patients in remission and those in relapse. The average IP of patients did not differ from the average IP of the control group, although patients with untreated celiac disease demonstrated increased IP. There were significant EDTA excretion differences between patients with celiac disease and both nonceliac patients and controls. Neuroleptic and antidepressant medications did not affect IP, and no relationship was found between schizophrenia and IP. Future epidemiological studies should assess whether or not celiac disease occurs more frequently in schizophrenia than in the general population. (Consumer Summary produced by Reliance Medical Information, Inc.)

Evaluation, Neurologic manifestations of general diseases, Neurologic manifestations

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