Dietary calcium decreases blood pressure without decreasing renal vascular resistance or altering the response to NO blockade

Many vasoactive elements are involved in the elevation of blood pressure in spontaneously hypertensive rats (SHR). Elevated dietary calcium has been observed to reduce blood pressure in SHR. This study investigates interactions among dietary calcium, renal vascular resistance (RVR), elevation of blood pressure and effects of norepinephrine and nitric oxide synthesis. We completed a series of experiments on two groups each (fed low, 0.1% and high, 2.0% dietary calcium, respectively) of 9-week-old Wistar Kyoto (WKY), 9-week-old and 6-week-old SHR. Although 9-week-old SHR had elevated baseline blood pressure compared to 9-week-old WKY and also compared to 6 week-old SHR, there was no corresponding elevation in baseline RVR. All SHR fed high calcium diets had lower blood pressure compared to low calcium diets, and there was no corresponding reduction in RVR. WKY controls' blood pressure and RVR were unaffected by dietary calcium levels. In all hypertensive rats the blood pressure and renal vascular resistance were elevated by N(G)-nitro-L-arginine methylester (L-NAME), but the dietary differences were sustained. Blood pressure of WKY was unaffected by the low dose of L-NAME. The increase in RVR to L-NAME was greater in SHR than in controls. The renal vascular response to norepinephrine was related to diet in older SHR, but smaller and unrelated to diet in younger SHR. Following L-NAME, WKY had greater responses to norepinephrine than 9-week-old SHR. We conclude that noradrenergic vasoconstriction is enhanced in the adult SHR, especially in the absence of high calcium diet. Alterations in NO synthesis may effect the norepinephrine response.     

Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial

CONTEXT: Orlistat, a gastrointestinal lipase inhibitor that reduces dietary fat absorption by approximately 30%, may promote weight loss and reduce cardiovascular risk factors. OBJECTIVE: To test the hypothesis that orlistat combined with dietary intervention is more effective than placebo plus diet for weight loss and maintenance over 2 years. DESIGN: Randomized, double-blind, placebo-controlled study conducted from October 1992 to October 1995. SETTING AND PARTICIPANTS: Obese adults (body mass index [weight in kilograms divided by the square of height in meters], 30-43 kg/m2) evaluated at 18 US research centers. INTERVENTION: Subjects received placebo plus a controlled-energy diet during a 4-week lead-in. On study day 1, the diet was continued and subjects were randomized to receive placebo 3 times a day or orlistat, 120 mg 3 times a day, for 52 weeks. After 52 weeks, subjects began a weight-maintenance diet, and the placebo group (n = 133) continued to receive placebo and orlistat-treated subjects were rerandomized to receive placebo 3 times a day (n = 138), orlistat, 60 mg (n = 152) or 120 mg (n = 153) 3 times a day, for an additional 52 weeks. MAIN OUTCOME MEASURES: Body weight change and changes in blood pressure and serum lipid, glucose, and insulin levels. RESULTS: A total of 1187 subjects entered the protocol, and 892 were randomly assigned on day 1 to double-blind treatment. For intent-to-treat analysis, 223 placebo-treated subjects and 657 orlistat-treated subjects were evaluated. During the first year orlistat-treated subjects lost more weight (mean +/- SEM, 8.76+/-0.37 kg) than placebo-treated subjects (5.81+/-0.67 kg) (P<.001). Subjects treated with orlistat, 120 mg 3 times a day, during year 1 and year 2 regained less weight during year 2 (3.2+/-0.45 kg; 35.2% regain) than those who received orlistat, 60 mg (4.26+/-0.57 kg; 51.3% regain), or placebo (5.63+/-0.42 kg; 63.4% regain) in year 2 (P<.001). Treatment with orlistat, 120 mg 3 times a day, was associated with improvements in fasting low-density lipoprotein cholesterol and insulin levels. CONCLUSIONS: Two-year treatment with orlistat plus diet significantly promotes weight loss, lessens weight regain, and improves some obesity-related disease risk factors.     

In vitro lipid peroxidation of LDL from postmenopausal cynomolgus macaques treated with female hormones

We constructed a sensitive and quantitative assay system to examine human T-cell leukemia virus type I (HTLV-I) envelope (env) glycoprotein-mediated cell fusion in which T7 RNA polymerase in donor cells coexpressing env glycoproteins activates a reporter gene in recipient cells upon cell fusion. An efficient expression of HTLV-I env glycoproteins (gp46 and gp21) was observed in 293T cells transfected with an expression plasmid by both immunoblot and immunofluorescence analyses. The cells expressing env glycoproteins also exhibited self-fusion. By cocultivating the donor cells with recipient cells transfected with a reporter plasmid possessing the luciferase gene under the T7 promoter, the expression of luciferase was observed upon cell fusion. The activation of the luciferase gene was inhibited by either anti-env neutralizing antibody or synthetic peptide corresponding to env gp21, thus indicating the cell fusion to be specifically mediated by the HTLV-I env glycoproteins expressed in the donor cells. A broad range of cell lines exhibited susceptibility to HTLV-I env-mediated cell fusion by this assay. This newly established assay system may thus provide an efficient way both to study the fusion mechanisms mediated by HTLV-I env glycoproteins and to identify the HTLV-I receptor(s).     

Neutrophil recruitment by human IL-17 via C-X-C chemokine release in the airways

IL-17 is a recently discovered cytokine that can be released from activated human CD4+ T lymphocytes. This study assessed the proinflammatory effects of human (h) IL-17 in the airways. In vitro, hIL-17 increased the release of IL-8 in human bronchial epithelial and venous endothelial cells, in a time- and concentration-dependent fashion. This effect of hIL-17 was inhibited by cotreatment with an anti-hIL-17 Ab and was potentiated by hTNF-alpha. In addition, hIL-17 increased the expression of hIL-8 mRNA in bronchial epithelial cells. Conditioned medium from hIL-17-treated bronchial epithelial cells increased human neutrophil migration in vitro. This effect was blocked by an anti-hIL-8 Ab. In vivo, intratracheal instillation of hIL-17 selectively recruited neutrophils into rat airways. This recruitment of neutrophils into the airways was inhibited by an anti-hIL-17 Ab and accompanied by increased levels of rat macrophage inflammatory protein-2 (rMIP-2) in bronchoalveolar lavage (BAL) fluid. The BAL neutrophilia was also blocked by an anti-rMIP-2 Ab. The effect of hIL-17 on the release of hIL-8 and rMIP-2 was also inhibited by glucocorticoids, in vitro and in vivo, respectively. These data demonstrate that hIL-17 can specifically and selectively recruit neutrophils into the airways via the release of C-X-C chemokines from bronchial epithelial cells and suggest a novel mechanism linking the activation of T-lymphocytes to recruitment of neutrophils into the airways.     

Functional MRI reveals spatially specific attentional modulation in human primary visual cortex

Selective visual attention can strongly influence perceptual processing, even for apparently low-level visual stimuli. Although it is largely accepted that attention modulates neural activity in extrastriate visual cortex, the extent to which attention operates in the first cortical stage, striate visual cortex (area V1), remains controversial. Here, functional MRI was used at high field strength (3 T) to study humans during attentionally demanding visual discriminations. Similar, robust attentional modulations were observed in both striate and extrastriate cortical areas. Functional mapping of cortical retinotopy demonstrates that attentional modulations were spatially specific, enhancing responses to attended stimuli and suppressing responses when attention was directed elsewhere. The spatial pattern of modulation reveals a complex attentional window that is consistent with object-based attention but is inconsistent with a simple attentional spotlight. These data suggest that neural processing in V1 is not governed simply by sensory stimulation, but, like extrastriate regions, V1 can be strongly and specifically influenced by attention.     

Metastatic head and neck cancer: role and usefulness of FDG PET in locating occult primary tumors

OBJECTIVE: Secondary intracranial hypertension has been linked to leukocytosis. We examined our data bank containing physiologic recordings and outcome data of severely head injured patients to investigate the relationship between delayed increases in intracranial pressure (ICP), defined as occurring after a 12-hr period of normal ICP values, and leukocytosis. DESIGN: A retrospective study of observational data. SETTING: Regional neurosurgical unit and intensive care unit. PATIENTS: Sixty-four patients suffered increased ICP >20 mm Hg. Thirty-five patients fulfilled selection criteria for delayed increases in ICP (group 1). Twenty-nine patients with increased ICP with no preceding or intervening periods of normal ICP were selected as a comparison group (group 2). MEASUREMENTS AND MAIN RESULTS: Comparison of 12-month outcome revealed that 11% of group 1 patients died, with 49% remaining severely disabled, in contrast to group 2, where 35% of patients died and 14% were left severely disabled (p = .021). The pattern of outcome was independent of monitoring time, or injury severity. Regression modeling was performed for prediction of delayed increase in ICP. Of 46 patients with an initial increase then decrease in leukocyte count in the first 48 hrs, 65% experienced delayed increases in ICP, as compared with 18% of the 11 patients without this pattern p = .01 1). CONCLUSIONS: Patients with delayed increases have a significantly different pattern of outcome. Change in leukocyte count from admission to day 2 is a significant predictor of such a delayed increase.     

Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes

Clinical evidence suggests that cellular immunity is involved in controlling human immunodeficiency virus-1 (HIV-1) replication. An animal model of acquired immune deficiency syndrome (AIDS), the simian immunodeficiency virus (SIV)-infected rhesus monkey, was used to show that virus replication is not controlled in monkeys depleted of CD8+ lymphocytes during primary SIV infection. Eliminating CD8+ lymphocytes from monkeys during chronic SIV infection resulted in a rapid and marked increase in viremia that was again suppressed coincident with the reappearance of SIV-specific CD8+ T cells. These results confirm the importance of cell-mediated immunity in controlling HIV-1 infection and support the exploration of vaccination approaches for preventing infection that will elicit these immune responses.     

Experimental demonstration that offspring sex ratio varies with maternal condition

Sex ratio theory predicts that, if prevailing ecological or social circumstances differentially influence the fitness benefits of offspring of each sex, parents should adjust their production accordingly to maximize fitness. For species in which sex is chromosomally determined, such as birds and mammals, a differential effect of maternal condition on the fitness of male and female young is one important route whereby selection is expected to favor a bias in the offspring sex ratio at birth or egg laying. However, despite its central place in sex allocation theory, this hypothesis has rarely been tested in wild populations. We manipulated maternal condition upward and downward in a sexually dimorphic wild bird and examined the effect on offspring survival and on offspring sex ratio. The survival to fledging of male, but not female, young was substantially reduced if they came from less well provisioned eggs produced by females in relatively poor condition. As female condition, and thereby her capacity to produce high quality eggs, declined, she progressively skewed the sex ratio of her eggs toward females; i.e., she produced more of the sex with the higher survival prospects. The decline in the survival of male offspring, and the sex ratio bias, was removed when maternal condition was enhanced. These results provide experimental evidence of an adaptive, facultative adjustment of sex ratio in response to changes in maternal condition in wild birds.     

Measurement of α particle energy loss in biological tissue below 2 MeV

The energy loss of α particles crossing biological tissue at energies between 0.8 and 2.2 MeV has been measured. This energy range is very important for boron neutron capture therapy, based on the ¹⁰B(n,α)⁷Li reaction, which emits α particles with energies of 1.78 and 1.47 MeV. One of the methods used for the measurement of the boron concentration in tissue is based on the deconvolution of the α spectra obtained from neutron irradiation of thin (70 μm) tissue samples. For this technique, a knowledge of the behaviour of the energy loss of the particles in the irradiated tissue is of critical importance. In particular, the curve of the residual energy as a function of the distance travelled in the tissue must be known. In this paper, the results of an experiment carried out with an ²⁴¹Am source and a series of cryostatic sections of rat-lung tissue are presented. The experimental measurements are compared with the results of Monte Carlo calculations performed with the MCNPX code.     

Inhibition of Aspergillus spp. and Penicillium spp. by fatty acids and their monoglycerides

The antifungal activity of three fatty acids (lauric, myristic, and palmitic acids) and their monoglycerides (monolaurin, monomyristic acid, and palmitin, respectively) against Aspergillus and Penicillium species in a model system was investigated. Data were modeled through a reparameterized Gompertz equation. The maximum colony diameter attained within the experimental time (30 days), the maximal radial growth rate, the lag time (i.e., the number of days before the beginning of radial fungal growth), and the minimum detection time (MDT; the number of days needed to attain 1 cm colony diameter) were evaluated. Fatty acids and their monoglycerides inhibited mold growth by increasing MDT and lag times. The effectiveness of the active compounds seemed to be strain and genus dependent. Palmitic acid was the most effective chemical against aspergilli, whereas penicilli were strongly inhibited by myristic acid. Aspergilli also were more susceptible to fatty acids than were penicilli, as indicated by the longer MDT.