Exploring the genetic and environmental etiology of high general cognitive ability in fourteen- to thirty-six-month-old twins

Two definitions of normality ("isolated" or "correlated") are considered. The boundaries of "isolated" normality were determined by a statistical procedure, whereas the "correlated" approach was related to a clinical or predictive definition. In the latter case, the biological variations were considered abnormal if they implied a hazard with some significant future ailment as a risk factor. In this pragmatic approach, the upper limit of normal/abnormal variations is the point beyond which medical strategy is related to the most expected benefit when applied to a definite population or to an individual patient. The capacity of a diagnostic test to discriminate between patients with a defined risk and those without risk depends strictly on the value of the parameter chosen. In medical care for the prevention of vascular complications in diabetic patients or with foetal risks in pregnant women, the limits of the so-called normal range of glycaemia and other parameters should be determined according to the objective of the preventive and/or therapeutic measures to be prescribed.     

Prophylactic efficacy of tilmicosin for bovine respiratory tract disease

The prophylactic administration of injectable tilmicosin for pneumonia in weaned beef calves was investigated in 1,806 animals. Comparisons were made among calves receiving an "on-arrival" injection of tilmicosin, calves receiving a single injection of long-acting oxytetracycline, and calves receiving no prophylaxis. Morbidity and mortality attributable to pneumonia, morbidity and mortality attributable to all causes, and case fatality were significantly lower in the group of calves that received tilmicosin, compared with calves that received long-acting oxytetracycline and calves that received no prophylactic antibiotic. Mean time to initial pneumonia treatment was significantly extended in calves that received prophylaxis, compared with those that received no antibiotic on arrival at the feedlot. Calves that received tilmicosin gained significantly more weight than calves that received oxytetracycline. Calves that were not treated for pneumonia during the trial period gained significantly more weight than did those calves that were treated for pneumonia regardless of experimental group. The majority of mortalities were attributable to fibrinous pneumonia (31/34). Important bacterial isolates (Pasteurella spp, Haemophilus somnus, Actinomyces pyogenes) obtained at necropsy did not have resistance to tilmicosin in association with administration of tilmicosin as prophylaxis for pneumonia. However, bacterial resistance to trimethoprim/sulfonamide and to oxytetracycline were commonly found in these postmortem isolates.     

Comparison of technetium-99m-ECD to Xenon-133 SPECT in normal controls and in patients with mild to moderate regional cerebral blood flow abnormalities

Technetium-99m-1,1-ethyl cysteinate dimer (ECD) has been proposed as a "chemical microsphere" for SPECT measurement of regional cerebral blood flow (rCBF). However, its distribution has not yet been compared in humans to an established rCBF measure. Therefore, we compared the uptake and distribution of ECD with rCBF measured by 133Xe SPECT in subjects with mild to moderate flow abnormalities and in normal volunteers. Blood and urine chemistries and vital signs were unchanged from pre-ECD values up to seven days postinjection. Profile plots demonstrated pattern agreement between rCBF ratios (133Xe) and ECD count density ratios. A significant correlation of rCBF ratios to ECD count density ratios was observed (r = 0.77), with a slope of 0.64 and intercept of 0.36. To explore whether or not the relationship between rCBF and ECD was dependent on absolute flow, ECD region of interest data were expressed in units of ml/min/100 g by equating global CBF (133Xe) and ECD global count density. A closer correlation (r = 0.88) was found for these data than for the count ratio data. The slope was closer to one (m = 0.83) and the intercept was closer to zero (b = 8.2). Also, a significant correlation was observed between ECD-derived rCBF and 133Xe rCBF in the lesion area (r = 0.92) for patients with well-demarcated rCBF lesions. The slope (0.80) suggested a slight underestimation of lesion flow by ECD. Finally, ECD clearance from cortical gray matter ROIs derived from high-resolution scans from 1 to 4 hr postinjection was slow (2.4%/hr). In summary, ECD is a safe and effective marker of regional cerebral perfusion. The distribution of ECD is linearly related to rCBF measured by 133Xe SPECT, although our data suggest a mild underestimation of flow at the high end of the normal range.     

Lycopene from two food sources does not affect antioxidant or cholesterol status of middle-aged adults

Background

Epidemiological studies have reported associations between reduced cardiovascular disease and diets rich in tomato and/or lycopene. Intervention studies have shown that lycopene-containing foods may reduce cholesterol levels and lipid peroxidation, factors implicated in the initiation of cardiovascular disease. The objective of this study was to determine whether consumption of lycopene rich foods conferred cardiovascular protection to middle-aged adults as indicated by plasma lipid concentrations and measures of ex vivo antioxidants.

Methods

Ten healthy men and women consumed a low lycopene diet with no added lycopene (control treatment) or supplemented with watermelon or tomato juice each containing 20 mg lycopene. Subjects consumed each treatment for three weeks in a crossover design. Plasma, collected weekly was analyzed for total cholesterol, high density lipoprotein cholesterol (HDL-C) and triglyceride concentrations and for the antioxidant biomarkers of malondialdehyde formation products (MDA), plasma glutathione peroxidase (GPX) and ferric reducing ability of plasma (FRAP). Data were analyzed using Proc Mixed Procedure and associations between antioxidant and lipid measures were identified by Pearson's product moment correlation analysis.

Results

Compared to the control diet, the lycopene-containing foods did not affect plasma lipid concentrations or antioxidant biomarkers. Women had higher total cholesterol, HDL-C and triglyceride concentrations than did the men. Total cholesterol was positively correlated to MDA and FRAP while HDL-C was positively correlated to MDA and GPX. GPX was negatively correlated to triglyceride concentration.

Conclusions

The inclusion of watermelon or tomato juice containing 20 mg lycopene did not affect plasma lipid concentrations or antioxidant status of healthy subjects. However, plasma cholesterol levels impacted the results of MDA and FRAP antioxidant tests.     

Synthesis and biological properties of novel pyridinioalkanoyl thiolesters (PATE) as anti-HIV-1 agents that target the viral nucleocapsid protein zinc fingers

Nucleocapsid p7 protein (NCp7) zinc finger domains of the human immunodeficiency virus type 1 (HIV-1) are being developed as antiviral targets due to their key roles in viral replication and their mutationally nonpermissive nature. On the basis of our experience with symmetrical disulfide benzamides (DIBAs; Rice et al. Science 1995, 270, 1194-1197), we synthesized and evaluated variants of these dimers, including sets of 4,4'- and 3,3'-disubstituted diphenyl sulfones and their monomeric benzisothiazolone derivatives (BITA). BITAs generally exhibited diminished antiviral potency when compared to their disulfide precursors. Novel, monomeric structures were created by linking haloalkanoyl groups to the benzamide ring through -NH-C(=O)- (amide) or -S-C(=O)- (thiolester) bridges. Amide-linked compounds generally lacked antiviral activity, while haloalkanoyl thiolesters and non-halogen-bearing analogues frequently exhibited acceptable antiviral potency, thus establishing thiolester benzamides per se as a new anti-HIV chemotype. Pyridinioalkanoyl thiolesters (PATEs) exhibited superior anti-HIV-1 activity with minimal cellular toxicity and appreciable water solubility. PATEs were shown to preferentially target the NCp7 Zn finger when tested against other molecular targets, thus identifying thiolester benzamides, and PATEs in particular, as novel NCp7 Zn finger inhibitors for in vivo studies.     

Visual system maldevelopment disrupts extraocular muscle-specific myosin expression

We measured hepatic albumin synthesis in five volunteers (4 men and 1 woman) at 3 and 6 h after recovery from intense exercise. A primed-constant infusion of a stable isotopic tracer of phenylalanine was used to determine hepatic fractional synthetic rate (FSR) and absolute synthetic rate (ASR) of albumin from the enrichment of phenylalanine in albumin. The infusion of the stable isotope tracer began 2 h after upright exercise or upright rest. Albumin FSR and ASR were 6.39 +/- 0.48%/day and 120 +/- 9 mg.kg body wt-1.day-1, respectively, 3-6 h after recovery from exercise; the FSR and ASR on the time control study day were 5.94 +/- 0.47%/day and 104 +/- 9 mg.kg body wt-1.day-1, respectively. The 6 and 16% increases (P < 0.05) in FSR and ASR after exercise were associated with an elevated plasma albumin content at 5 and 6 h of recovery (P < 0.05), an increased total protein content throughout recovery (P < 0.05), and a negative free water clearance (P < 0.05) at 2, 3, and 6.5 h of recovery compared with baseline values; these variables were unchanged from their baselines on the time control study day. Increased albumin content and reduced free water clearance contribute to a retention of fluid within the circulation after intense exercise. The measured increase in albumin synthesis could not account for the entire increase in albumin content at 6 h of recovery from exercise. However, we estimate that if the increased activity was maintained for the next 18 h, it could account for the expected increase in albumin content at 24 h of recovery.     

Classical/nonclassical hybrid cannabinoids: southern aliphatic chain-functionalized C-6beta methyl, ethyl, and propyl analogues

The stereoelectronic requirements for interaction of the southern aliphatic hydroxyl of cannabimimetic pharmacophores with the CB1 and CB2 receptors are explored. The stereoselective syntheses of three series of classical/nonclassical hybrid cannabinoids are described. These compounds were designed to investigate the importance of the southern aliphatic hydroxyl (SAH) pharmacophore for cannabimimetic activity. Variation in the chain length of the SAH moiety in these 6beta-(hydroxyalkyl)dihydrobenzopyran analogues, from 6beta-hydroxymethyl to 6beta-(omega-hydroxyethyl) and 6beta-(omega-hydroxypropyl), and the effects of replacing the hydroxyl functionality by hydride and iodide are reported. Our results indicate that the SAH pharmacophore has less pronounced effects than the C-3 aliphatic chain on cannabinoid activity. Furthermore, it appears that this southern molecular component is capable of interacting with two different subsites on the receptor and that the nature of this interaction is determined by the terminal substituent on the C-6beta alkyl group. One of the subsites can accommodate the relatively polar SAH pharmacophore, while the second subsite interacts with more hydrophobic C-6beta substituents and can accommodate large spherical pharmacophores separated by three methylene carbons from the tricyclic cannabinoid template.