Association of upper gastrointestinal toxicity of non-steroidal anti-inflammatory drugs with continued exposure: cohort study.

OBJECTIVES: To determine the profile of risk of upper gastrointestinal toxicity during continuous treatment with, and after cessation of, non-steroidal anti-inflammatory drugs. DESIGN: Cohort study with a prospectively constructed, population based, record linkage database containing details of exposure to all community dispensed non-steroidal anti-inflammatory drugs and also all admissions to hospital for upper gastrointestinal diagnoses. SETTING: The population of Tayside, Scotland. SUBJECTS: 52,293 subjects aged 50 and over who received one or more non-steroidal anti-inflammatory between 1 January 1989 and 31 December 1991 and 73,792 subjects who did not receive one during the same period (controls). MAIN OUTCOME MEASURES: Admission to hospital for upper gastrointestinal bleeding and perforation, and admission for other upper gastrointestinal diagnoses. RESULTS: About 2% of the non-steroidal anti-inflammatory cohort were admitted with an upper gastrointestinal event during the study period compared with 1.4% of controls. The risk of admission for upper gastrointestinal haemorrhage and perforation was constant during continuous non-steroidal anti-inflammatory exposure and carried over after the end of exposure. The results were similar for admissions for all upper gastrointestinal events. CONCLUSION: This study provides evidence that non-steroidal anti-inflammatory toxicity persists with continuous exposure. There seems to be carryover toxicity after the end of prescribing. These findings have implications for the management of patients requiring non-steroidal anti-inflammatory drugs.     

DNA topology: Topoisomerases keep it simple

The ability of type II DNA topoisomerases to perturb the equilibrium distributions of DNA topoisomers is a consequence of their ability to hydrolyse ATP. A sliding mechanism of topoisomerase action has been proposed to account for this phenomenon.     

Localization of corticotropin-releasing factor-containing neurons in the brain of the domestic fowl

Summary The corticotropin-releasing factor (CRF)-containing neurons were investigated in the brain of the domestic fowl by means of the peroxidase-antiperoxidase technique at the light-microscopic level. The detection of CRF-immunoreactivity was facilitated by silver intensification. CRF-containing perikarya were found in the paraventricular, preoptic and mammillary nuclei of the hypothalamus and in some extrahypothalamic areas (nuclei dorsomedialis and dorsolateralis thalami, nucleus accumbens septi, lobus parolfactorius, periaqueductal gray of the mesencephalon, nucleus oculomotorius ventralis). Immunoreactive nerve fibers and terminals were demonstrated in the external zone of the median eminence and the organum vasculosum of the lamina terminalis. These results indicate that an immunologically demonstrable CRF-neurosecretory system also exists in the avian central nervous system.     

Cell interactions during the fusionin vitro ofDrosophila eye-antennal imaginal discs

Summary The fusion of the eye-antennal discs during culturein vitro has been investigated, and the complex morphogenetic movements which occur during the formation of the head capsule of the insect are described. The initial contact between the eye anlagen is by means of cell processes spanning the gap between the two discs. Subsequently the two epithelia become firmly apposed, and then the integrity of the epithelium in the region of fusion breaks down, cells appearing to move to new positions in order to form an epithelium which unites the two discs. The epithelium eventually secretes a pattern of cuticular structures which is continuous between the derivatives of the two discs. Bristles on either side of the line of fusion are perfectly aligned, and structures such as the median ocellus, which are formed jointly by the cells of the two discs, differentiate normally. This is also found when left and right eye-antennal discs of different genotypes are placed side-by-side, indicating that processes of pattern regulation can occur in culture.     

Iron hydroxide: Model for enzymes that oxidize proteins

The particles of an iron hydroxide sol were found to be a suitable model for protein-oxidizing enzymes such as peroxidase and polyphenol oxidase. In addition to small molecules such as pyrogallol, human serum proteins, albumin and -globulin, are shown to be substrates of the oxidizing model. The activity is markedly increased by the addition of small amounts of copper to the iron in the particles of the sol. The size and molecular weight of the enzyme model, as well as the number of active centers were determined.     

Kidney grafting between rats which carry recombinant major histocompatibility haplotypes

Kidney transplantation was performed between three congenic rat strains which carried the major histocompatibility haplotypesRT1 ^a ,RT1 ^u orRT1 ^ar1 , the latter being a recombinant betweenRT1 ^a andRT1 ^u . This combination made it possible to test separately the effects of incompatibility for RT1. A-region products (classical transplantation antigens, histocompatibility antigens) and for RT1.B-region products (Ia-antigens, strong mixed lymphocyte stimulating antigens, histocompatibility antigens) as well as RT1.C-region products (lymphocyte differentiation antigens, histocompatibility antigens). It is shown that A plus B plus C, as well as A or B plus C-region incompatibility led to kidney-graft rejection and that matching for either classical transplantation antigens or Ia and strong mixed lymphocyte stimulating antigens had no clear differential prognostic effect on kidney-graft survival.     

Two-stage fermentation method for production of protein-enriched feed from cassava

Studies have been carried out into the production of microbial protein from cassava using Trichoderma reesei and yeast. In monoculture studies, T. reesei was grown on whole cassava medium to give 0.74g dry cell/g cassava. The dry material contained 42% protein. The culture filtrate contained 5.8 g/l glucose, which supported the growth of yeast. Mixed culture fermentation was also carried out with the two microorganisms. Besides accelerating the rate of degradation and conversion of cassava to cells (0.85g cell/g cassava) the yeast boosted the protein content of the growth product to 51%.