Agonists and antagonists for lipopolysaccharide-induced cytokines

Agonistic and antagonistic properties of LPS and partial structures in the induction of cytokines are reviewed. Studies on structure-activity relationships of LPS and lipid A with human mononuclear cells reveal that S- and notably R-form LPS are very potent cytokine inducers. Synthetic E. coli lipid A is somewhat less active, whereas synthetic S. minnesota-type lipid A is significantly less active. Pentaacylated forms of lipid A are less potent than hexaacylated forms, and tetraacylated synthetic precursor Ia and bisacylated disaccharides and monosaccharides are completely inactive, indicating that a structure-dependent hierarchy of LPS and lipid A partial structures determines the monokine-inducing capacity in human mononuclear cells. Precursor Ia is a potent LPS antagonist. The mechanism of its inhibitory activity is shown to be due to competitive binding to cellular binding sites (receptors). Proinflammatory and antiinflammatory cytokines, receptor antagonists, and soluble cytokine receptors influence the cytokine-inducing activity of LPS, suggesting a complex regulatory network.     

Adverse effects of wide calcium:phosphorus ratios on supplemental phytase efficacy for weanling pigs fed two dietary phosphorus levels

Ninety-six weanling pigs (initial BW = 9.3 kg, initial age = 37 d) were used in a 4-wk experiment to evaluate the response to three Ca: total (t) P ratios (1.2:1, 1.6:1, or 2.0:1) fed in combination with two P levels (.07 or .16% available that correspond to .36 or .45% tP) and two phytase levels (PY; 700 or 1,050 units/kg of diet). A 3 x 2 x 2 factorial arrangement of treatments was employed using a corn-soybean meal diet. Performance, serum mineral concentrations and alkaline phosphatase (ALP) activity, Ca and P digestibility and excretion, and bone mechanical measurements were examined. Average daily gain (P < .001), average daily feed intake (P < .01), and gain:feed (P < .05) were decreased linearly as the Ca:tP ratio became wider. The digestibility of P and Ca were decreased (P < .001) linearly as the Ca:tP ratio became wider. The digestibility of P (P < .001) and fecal P excretion (P < .01) were increased at the higher level of P. Increasing PY from 700 to 1,050 units (U)/kg of diet increased (P < .05) P digestibility and decreased (P < .01) P excretion but did not improve bone measurements. Shear force, stress and energy, and percentage of ash of both metacarpal and 10th rib linearly decreased (P < .001 to .05) as the Ca:tP ratio became wider, and bone measurements were generally greater for pigs fed the higher P level. Serum Ca concentration increased (P < .01) and the P concentration decreased (P < .001) as the Ca:tP ratio increased, but Mg, Zn, and ALP activity were not influenced by the Ca:tP ratio. Serum Ca and P concentrations were affected by PY supplementation over the 4-wk trial, but serum Mg and Zn concentrations were not affected by dietary treatments. Adverse effects of a wide Ca:tP ratio were greater at the low P diet for all responses. In addition, the activity of supplemental PY in diets seemed to be decreased as the Ca:tP ratio became wider and this negative effect of Ca:tP ratio seemed greater at the low P level, and seemed to parallel the effects of Ca:tP ratio on performance, P digestibility, bone, and serum measurements. Narrowing the dietary Ca:total P ratio from 2.0:1 to 1.2:1 led to an approximate 16% increase in phytase efficacy for improving performance, digestibility, bone measurements, and serum Ca levels.     

Completed suicide among adolescents with no diagnosable psychiatric disorder

The characteristics of male adolescent suicide victims with (n = 84) and without (n = 8) a diagnosable psychiatric disorder were compared. Using psychological autopsy methods--interviews with victims' family members and health care professionals, and review of records (e.g., medical, school, police)-data were collected on all adolescent suicides in Finland during a 12-month period. Compared with adolescents with a psychiatric disorder, those with no disorder tended to come from less disturbed families, had shown less antisocial behavior, and had less frequently utilized health care and social services. Adolescents with no disorder more often communicated suicidal thoughts for the first time just before the suicide, and difficulties with the law (discipline problems) were more common precipitants than among those with a disorder. It was concluded that the process leading to suicide seems to be relatively short among male adolescents with no diagnosable psychiatric disorder. Communication of suicidal intent and problems with discipline are among the few clinical warning signs.     

Comparative evaluation of reactogenicity and immunogenicity of two dosages of oral tetravalent rhesus rotavirus vaccine. US Rhesus Rotavirus Vaccine Study Group

OBJECTIVE: To compare the safety and immunogenicity of two dosages of tetravalent rhesus rotavirus vaccine (RRV-TV) and the effect of age at dosing. METHODS: A total of 195 infants were stratified by age into 2 groups, 6 to 12 weeks and 16 to 24 weeks, and randomly assigned to receive a single dose of placebo or RRV-TV containing either 4 x 10(5) or 4 x 10(6) plaque-forming units (pfu). Symptoms were recorded for 5 days after vaccination. Anti-rotavirus IgA and neutralizing antibody to human rotavirus serotypes G1 to G4 and RRV were measured in serum obtained pre- and postvaccination. RESULTS: Rates of fever > 38 degrees C (9%), diarrhea (6%) and vomiting (8%) were similar in all groups. IgA (69% vs. 49%, P = 0.02) and RRV (85% vs. 66%, P = 0.004) seroconversion rates were significantly higher in the 4 x 10(6) pfu vaccine group as were antibody titers to RRV (440.2 vs. 263.7, P = 0.04). Older infants demonstrated significantly higher seroconversion rates and antibody titers for IgA (71% vs. 52%, P = 0.03; and 110.6 vs. 54.8, P = 0.004) and RRV (92% vs. 66%, P = 0.05 and 498.3 vs. 205.6, P = 0.01) at either dose level than did the younger infants. There were no significant differences in seroconversion rates or antibody titers to human rotavirus types G1 to G4 between the two vaccination groups. CONCLUSIONS: RRV-TV at a dose of 4 x 10(6) pfu can be safely administered to infants 6 to 24 weeks of age. A single dose of 4 x 10(6) pfu of RRV-TV was significantly more immunogenic than a single dose of 4 x 10(5) pfu but did not improve responses to the human serotypes. Older vaccine recipients demonstrated significantly higher IgA and neutralizing antibody seroconversion rates and antibody titers than younger infants independent of dosage.     

Developmental characteristics of histamine methyltransferase and phenylethanolamine-N-methyl-transferase of rat brain

The specific activity of histamine methyltransferase of rat brain increases rapidly from the 16th until the 25th day of gestation (7 days after birth). The specific activity of phenylethanolamine-N-methyl-transferase shows a rapid increase during the 1st and the 2nd week after birth, the adult values being obtained by the end of the 2nd week.     

Greater rate of decline in maximal aerobic capacity with age in physically active vs. sedentary healthy women

Using a meta-analytic approach, we recently reported that the rate of decline in maximal oxygen uptake (VO2 max) with age in healthy women is greatest in the most physically active and smallest in the least active when expressed in milliliters per kilogram per minute per decade. We tested this hypothesis prospectively under well-controlled laboratory conditions by studying 156 healthy, nonobese women (age 20-75 yr): 84 endurance-trained runners (ET) and 72 sedentary subjects (S). ET were matched across the age range for age-adjusted 10-km running performance. Body mass was positively related with age in S but not in ET. Fat-free mass was not different with age in ET or S. Maximal respiratory exchange ratio and rating of perceived exertion were similar across age in ET and S, suggesting equivalent voluntary maximal efforts. There was a significant but modest decline in running mileage, frequency, and speed with advancing age in ET. VO2 max (ml . kg-1 . min-1) was inversely related to age (P < 0.001) in ET (r = -0.82) and S (r = -0.71) and was higher at any age in ET. Consistent with our meta-analysic findings, the absolute rate of decline in VO2 max was greater in ET (-5.7 ml . kg-1 . min-1 . decade-1) compared with S (-3.2 ml . kg-1 . min-1 . decade-1; P < 0. 01), but the relative (%) rate of decline was similar (-9.7 vs -9. 1%/decade; not significant). The greater absolute rate of decline in VO2 max in ET compared with S was not associated with a greater rate of decline in maximal heart rate (-5.6 vs. -6.2 beats . min-1 . decade-1), nor was it related to training factors. The present cross-sectional findings provide additional evidence that the absolute, but not the relative, rate of decline in maximal aerobic capacity with age may be greater in highly physically active women compared with their sedentary healthy peers. This difference does not appear to be related to age-associated changes in maximal heart rate, body composition, or training factors.