Modulation of human CACO-2 intestinal epithelial cell phenotype by protein kinase C inhibitors

Protein kinase C (PKC) isoforms are altered in colon tumors and upon exposure of intestinal mucosa to nutrients. We evaluated the effects of the PKC inhibitors staurosporine and calphostin C on human Caco-2 intestinal epithelial proliferation, motility, and differentiation. Motility was quantitated by monolayer expansion and the brush border enzymes dipeptidyl dipeptidase (DPDD) and alkaline phosphatase (AP) by synthetic substrate digestion. Staurosporine (0.03-1.0 ng/ml) and calphostin C (10(-12) M-10(-4) M) dose-dependently inhibited monolayer expansion and AP but stimulated DPDD. Proliferation was also inhibited but the effects of each inhibitor on motility, AP, and DPDD were preserved after mitomycin C proliferative blockade, suggesting that these effects were proliferation-independent. PKC inhibitors independently inhibit motility, AP and proliferation in human intestinal Caco-2 epithelial cells, but selectively stimulate the small intestinal differentiation marker DPDD. PKC may regulate small intestinal epithelial differentiation.     

Palatability of prerigor cooked boar meat

Cooking reduces odor intensity in boar meat but also may induce lipid oxidation unless the meat pH is above approximately 6.0. This research was designed to determine the feasibility of cooking boar meat in the prerigor state to overcome boar odor and lipid oxidation problems. Prerigor and postrigor triceps brachii muscle samples from 40 boars (20 Duroc and 20 Yorkshire) were cooked to 60 degrees C, frozen and stored at -20 degrees C, reheated in a 60 degrees C water bath for 1 h, and then subjected to pH, thiobarbituric acid (TBA), and sensory analyses. Boar odor intensity and skatole concentration in backfat samples were determined by olfactory test and HPLC, respectively. Cooked (initial cooking) prerigor meat was found to have higher (P < .05) pH and lower (P < .05) TBA values than comparable postrigor meat (6.44 vs 6.09 and 2.15 vs 3.23, respectively). Regression analysis indicated an inverse relationship between pH and TBA values (r = -.52; P < .01). No appreciable changes in TBA values were noted after frozen storage for 14 to 98 d, but reheating increased TBA values (P < .05) in both prerigor and postrigor samples (3.45 vs 4.32, respectively). Sensory evaluation scores indicated that prerigor cooked meat was less tender with more pronounced rancid flavor than postrigor cooked meat (P < .05), but panelists may have allowed the toughness of the prerigor samples to adversely affect their flavor scores. No difference in boar odor was detected between rigor states or breeds. Mean skatole concentration in backfat was .12 micrograms/g and no difference was detected between breeds.(ABSTRACT TRUNCATED AT 250 WORDS)     

Enhanced antibody response in Venezuelan infants immunized with Haemophilus influenzae type b-tetanus toxoid conjugate vaccine

The safety and immunogenicity of primary immunization at 2, 4 and 6 months of age with Haemophilus influenzae type b capsular polysaccharide conjugated to tetanus toxoid (PRP-T; Act-HIB) were evaluated in infants in Valencia, Venezuela. In order better to assess reactions to PRP-T, subjects received their initial PRP-T vaccine a mean of 6.5 days after their initial diphtheria-tetanus-pertussis (DTP) vaccine. The PRP-T vaccine was well tolerated. Serum was obtained at ages 2 and 7 months (before the first and 1 month after the third PRP-T dose). Antibody responses were compared with those from Nashville infants who had received PRP-T and DTP simultaneously in a previous trial. The preimmunization titers in the Venezuelan and Nashville infants did not differ. The geometric mean postimmunization titer in the Venezuelan infants was 37.9 micrograms/ml, as compared with 3.63 micrograms/ml in the Nashville infants (P < 0.00001). Possible explanations for the exceptional antibody response of these Venezuelan infants to PRP-T include carrier priming caused by prior DTP immunization, synergy associated with the specific DTP vaccine used, preimmunization immunologic experience that differed from their United States counterparts and genetic differences that altered response to the vaccines. Further studies are proposed to evaluate these possibilities.     

Neutron and X-ray reflectivity studies of human serum albumin adsorption onto functionalized surfaces of self-assembled monolayers

Endurance exercise training increases fat oxidation during large muscle mass exercise. Although the source of this fat has been thought to be plasma free fatty acids (FFA) released from adipose tissue, the training-induced decrease in lipolytic hormonal responses to exercise is not consistent with this concept. The purpose of this communication is to review findings, from our laboratory indicating that, in young healthy subjects, endurance exercise training reduces plasma FFA turnover and oxidation during moderate intensity prolonged 2-leg cycling while simultaneously enhancing depletion of triglycerides from the active musculature. Evidence is presented that metabolism of intramuscular triglycerides can explain the increase in total fat oxidation observed in the trained state during large muscle mass exercise. However, these results may not be applicable to exercise involving small muscle groups, a distinction that is likely to be important in explaining the apparent conflict between our findings and those from other laboratories where experimental conditions were different. In summary, for large muscle mass exercise up to 2 h in duration, plasma FFA are a less important fuel source in the trained state, and intramuscular triglycerides supply the major portion of the increase in oxidized fatty acids.     

Optic chiasm astrocytomas of childhood. 1. Long-term follow-up

There are many in vivo animal models for studying airway mucus secretion and hypersecretion, each with advantages and disadvantages. Use of a particular test system will depend upon the aspect of secretion to be modelled. Airway hypersecretory diseases exhibit chronic mucus hypersecretion, of which the clinical impact is predominantly in the distal airways. The majority of documented test preparations study acute secretion, invariably using tracheal preparations, but have been invaluable in elucidating the normal physiology of airway mucus secretion. Chronic models of the hypersecretory state in the distal airways have been developed, but are predominantly histologic in nature (for example quantification of increased goblet cell number). There are few investigations of mucus hypersecretion. Examination of the 'antisecretory' potential of pharmaceutical compounds has been investigated predominantly in chronic histologic models with the drug being given 'prophylactically' rather than 'therapeutically'. Refinement of chronic hypersecretory models should lead to elucidation of the connection between airway irritation, inflammation, MUC gene expression, mucous cell hyperplasia/metaplasia, airway hypersecretion and bronchial hypersecretory disease.     

Thyroid status and exercise tolerance. Cardiovascular and metabolic considerations

Both hypo- and hyperthyroidism are characterised by exercise intolerance. In hypothyroidism, inadequate cardiovascular support appears to be the principal factor involved. Insufficient skeletal muscle blood flow compromises exercise capacity via reduced oxygen delivery, and endurance through decreased delivery of blood-borne substrates. The latter effect results in increased dependence on intramuscular glycogen. Additionally, decreased mobilisation of free fatty acids from adipose tissue and, consequently, lower plasma free fatty acid levels compound the problem of reduced lipid delivery to active skeletal muscle in the hypothyroid state. In contrast, cardiovascular support is enhanced in hyperthyroidism, implicating other factors in exercise tolerance. Greater reliance on muscle glycogen appears to be the primary reason for decreased endurance. Biochemical changes with hyperthyroidism that would favour enhanced flux through glycolysis may account for this dependence on glycogen. Deviations from normal thyroid function, and the ensuing exercise tolerance, require appropriate medical therapy to attain euthyroid status.