The effects of dietary selenomethionine on polyamines and azoxymethane-induced aberrant crypts

We evaluated the effects of dietary selenomethionine supplementation on colonic polyamine levels and the ability of L-selenomethionine supplementation to modulate the carcinogenic activity of azoxymethane (AOM) in the rat colon. Four-week-old male F344 rats were treated with 15 mg/kg body weight of AOM once a week for 2 weeks. Dietary selenomethionine at a concentration of either 1 or 2 ppm was administered in AIN-76A rodent diet to AOM-treated animals for 16 weeks. Aberrant crypt foci (ACF), precursor lesions of colon cancer, were investigated after the 16 week treatment course. Selenomethionine given in the diet at 2 ppm markedly reduced the number of aberrant crypt foci. The multiplicity of ACFs (i.e. the number of aberrant crypts/focus) and the percentage of microadenomas were also affected by selenomethionine in a dose dependent manner. However, evaluation of the colonic tissue polyamine levels between control and treated groups showed no significant difference. These results demonstrate that selenomethionine can modulate the development of AOM-induced premalignant lesions through a polyamine-independent mechanism.     

A phenomenological difference between membrane skeletal protein complexes isolated from normal and hereditary spherocytosis erythrocytes

S ummary . Membrane skeletons may be obtained from human erythrocytes by extraction with non-ionic detergent. When treated under defined conditions with a cAMP-independent kinase preparation from normal membranes, a suspension of these membrane skeletons sets to a gelatinous mass. Membrane skeletons from the cells of hereditary spherocytosis patients fail to show this response. Those from subjects with some other haemolytic anaemias do not share the abnormality. The gelation process could be shown also to occur with normal membrane skeletons, extracted at high ionic strength, and containing essentially only the structural protein constituents, spectrin, actin, 4·1 and 4·9. It also occurred rapidly when a column-purified kinase preparation was used, so that no significant amounts of contaminating proteins were introduced. Added spectrin, 4·1 or actin in moderate amounts did not induce gelation in the presence of ATP. Cytochalasin E did not perturb the gelation process. Gelation required ATP as well as kinase, and did not occur when the non-hydrolysable analogue, AMP-PNP, was used instead. Gelation was accompanied by phosphorylation of the spectrin alone, and is thus evidently a consequence of the modification of its properties by this means. Inhibition of phosphorylation by added adenosine retarded gelation. It may be inferred that phosphorylation of spectrin generates new, probably weak, non-covalent interactions between cytoskeletal constituents that cause association of the isolated cytoskeletons. A semi-quantitative method of observing the gelation process, based on the time of incubation before the membrane skeleton suspension ceases to flow under gravity a t a low shear. is described.     

Psychosocial profiling: a holistic management tool for non-compliance

We introduce a new concept of psychosocial profiling as a tool that provides the transplant team with a psychosocial framework for identification, intervention and management of non-compliance. This will also increase our understanding of emotional problems experienced by patients before transplant, as a result of living with the uncertainty and medical side effects of chronic illness. Psychosocial profiling is adaptable throughout the transplant process and gives every patient an opportunity of psychosocial support to help him or her into a position of emotional stability and compliance with their medications and postoperative care. Implementation of this strategy will move health care professionals from being gatekeepers to managers and facilitators of holistic care in recipients of transplants.     

Glucose in bronchial aspirates increases the risk of respiratory MRSA in intubated patients

BACKGROUND: The risk of nosocomial infection is increased in critically ill patients by stress hyperglycaemia. Glucose is not normally detectable in airway secretions but appears as blood glucose levels exceed 6.7-9.7 mmol/l. We hypothesise that the presence of glucose in airway secretions in these patients predisposes to respiratory infection. METHODS: An association between glucose in bronchial aspirates and nosocomial respiratory infection was examined in 98 critically ill patients. Patients were included if they were expected to require ventilation for more than 48 hours. Bronchial aspirates were analysed for glucose and sent twice weekly for microbiological analysis and whenever an infection was suspected. RESULTS: Glucose was detected in bronchial aspirates of 58 of the 98 patients. These patients were more likely to have pathogenic bacteria than patients without glucose detected in bronchial aspirates (relative risk 2.4 (95% CI 1.5 to 3.8)). Patients with glucose were much more likely to have methicillin resistant Staphylococcus aureus (MRSA) than those without glucose in bronchial aspirates (relative risk 2.1 (95% CI 1.2 to 3.8)). Patients who became colonised or infected with MRSA had more infiltrates on their chest radiograph (p<0.001), an increased C reactive protein level (p<0.05), and a longer stay in the intensive care unit (p<0.01). Length of stay did not determine which patients acquired MRSA. CONCLUSION: The results imply a relationship between the presence of glucose in the airway and a risk of colonisation or infection with pathogenic bacteria including MRSA.     

Estrogen and progesterone regulate alpha, beta, and gammaENaC subunit mRNA levels in female rat kidney

BACKGROUND: Estrogen and progesterone regulate alpha, beta, and gamma amiloride-sensitive epithelial sodium channel (ENaC) subunit mRNA levels in female rat kidney. Renal Na(+) handling differs between males and females. Further, within females Na(+) metabolism changes during the menstrual cycle and pregnancy. Electrolyte homeostasis and extracellular fluid volume are maintained primarily by regulated transport of Na(+) via the amiloride-sensitive Na(+) channel. This study examines the role of the female gender steroids in the regulation of expression of ENaC. METHODS: We measured ENaC subunit mRNA levels in rat kidney using Northern blotting. Kidneys were taken from male and females at different ages and from adult ovariectomized rats treated with 17-beta-estradiol benzoate (estrogen) and/or progesterone for 8 or 24 hours. RESULTS: The abundance of alpha, beta, and gammaENaC mRNA was significantly higher in female compared to male rat kidneys from 10 weeks of age (P= 0.001, P= 0.004, and P= 0.02, N= 10, respectively). These differences were abolished in ovariectomized rats. Treatment of ovariectomized rats with estrogen increased alphaENaC mRNA abundance in the kidney at both 8 and 24 hours (P < 0.05, N= 6; and P < 0.05, N= 7, respectively). Progesterone inhibited the effect of estrogen on alphaENaC mRNA at 8 hours but when given alone increased gammaENaC mRNA (P < 0.05, N= 3). Neither hormone, alone or in combination, had any significant effect on betaENaC mRNA levels at 8 or 24 hours. CONCLUSION: Female gonadal steroids differentially modulate expression of ENaC subunit mRNA in the rat kidney.