Acute impact of aerobic exercise on local cutaneous thermal hyperaemia.

Little is known about the acute changes in cutaneous microvascular function that occur in response to exercise, the accumulation of which may provide the basis for beneficial chronic cutaneous vascular adaptations. Therefore, we examined the effects of acute exercise on cutaneous thermal hyperaemia. Twelve healthy, recreationally active participants (11 male, 1 female) performed 30-minute cycling at 50 % (low-intensity exercise, LOW) or 75 % (high-intensity exercise, HIGH) maximum heart rate. Laser Doppler flowmetry (LDF) and rapid local skin heating were used to quantify cutaneous thermal hyperaemia before (PRE), immediately following (IMM) and 1-h (1HR) after exercise. Baseline, axon reflex peak, axon reflex nadir, plateau, maximum skin blood flow responses to rapid local heating (42 °C for 30-min followed by 44 °C for 15-min) at each stage were assessed and indexed as cutaneous vascular conductance [CVC = flux / mean arterial blood pressure (MAP), PU·mm Hg-1], and expressed as a percentage of maximum (%CVCmax). Exercise increased heart rate (HR), MAP and skin blood flow (all P < 0.001), and to a greater extent during HIGH (all P < 0.001). The axon reflex peak and nadir were increased immediately and 1-h after exercise (all comparisons P < 0.01 vs. PRE), which did not differ between intensities (peak: P = 0.34, axon reflex nadir: P = 0.91). The endothelium-dependent plateau response was slightly elevated after exercise (P = 0.06), with no effect of intensity (P = 0.58) nor any interaction effect (P = 0.55). CONCLUSION: Exercise increases cutaneous microvascular axonal responses to local heating for up to 1-h, suggesting an augmented sensory afferent function post-exercise. Acute exercise may only modestly affect endothelial function in cutaneous microcirculation.

Concentration-dependent mobility, retardation, and speciation of iodine in surface sediment from the Savannah River Site.

Iodine occurs in multiple oxidation states in aquatic systems in the form of organic and inorganic species. This feature leads to complex biogeochemical cycling of stable iodine and its long-lived isotope, (129)I. In this study, we investigated the sorption, transport, and interconversion of iodine species by comparing their mobility in groundwaters at ambient concentrations of iodine species (10(-8) to 10(-7) M) to those at artificially elevated concentrations (78.7 µM), which often are used in laboratory analyses. Results demonstrate that the mobility of iodine species greatly depends on, in addition to the type of species, the iodine concentration used, presumably limited by the number of surface organic carbon binding sites to form covalent bonds. At ambient concentrations, iodide and iodate were significantly retarded (K(d) values as high as 49 mL g(-1)), whereas at concentrations of 78.7 µM, iodide traveled along with the water without retardation. Appreciable amounts of iodide during transport were retained in soils due to iodination of organic carbon, specifically retained by aromatic carbon. At high input concentration of iodate (78.7 µM), iodate was found to be reduced to iodide and subsequently followed the transport behavior of iodide. These experiments underscore the importance of studying iodine geochemistry at ambient concentrations and demonstrate the dynamic nature of their speciation during transport conditions.

Obesity, pregnancy, inflammation, and vascular function.

Maternal obesity is associated with increased morbidity and mortality for both mother and offspring. The mechanisms underlying the increased risk associated with maternal obesity are not well understood. In non-pregnant populations, many of the complications of obesity are thought to be mediated in part by inflammation and its sequelae. Recent studies suggest that a heightened inflammatory response may also be involved in mediating adverse clinical outcomes during pregnancy. This review summarizes our current knowledge about adipose tissue biology, and its role as an endocrine and inflammatory organ. The evidence for inflammation as a key mediator of adverse pregnancy outcome is also presented, focusing on the role of inflammation in adipose tissue, systemic inflammation, the placenta, and vascular endothelium.

A novel approach for the simultaneous determination of iodide, iodate and organo-iodide for 127I and 129I in environmental samples using gas chromatography-mass spectrometry.

In aquatic environments, iodine mainly exists as iodide, iodate, and organic iodine. The high mobility of iodine in aquatic systems has led to (129)I contamination problems at sites where nuclear fuel has been reprocessed, such as the F-area of Savannah River Site. In order to assess the distribution of (129)I and stable (127)I in environmental systems, a sensitive and rapid method was developed which enables determination of isotopic ratios of speciated iodine. Iodide concentrations were quantified using gas chromatography-mass spectrometry (GC-MS) after derivatization to 4-iodo-N,N-dimethylaniline. Iodate concentrations were quantified by measuring the difference of iodide concentrations in the solution before and after reduction by Na(2)S(2)O(5). Total iodine, including inorganic and organic iodine, was determined after conversion to iodate by combustion at 900 °C. Organo-iodine was calculated as the difference between the total iodine and total inorganic iodine (iodide and iodate). The detection limits of iodide-127 and iodate-127 were 0.34 nM and 1.11 nM, respectively, whereas the detection limits for both iodide-129 and iodate-129 was 0.08 nM (i.e., 2pCi (129)I/L). This method was successfully applied to water samples from the contaminated Savannah River Site, South Carolina, and more pristine Galveston Bay, Texas.

Hemodynamic performance of mitroflow aortic pericardial bioprosthesis - optimizing management for the small aortic annulus.

BACKGROUND: Documentation of the hemodynamics of the Mitroflow aortic pericardial bioprosthesis has been incomplete. The aim of the study was to provide reference effective orifice areas for the implant calculation of effective orifice area indexes to avoid prosthesis-patient mismatch. METHODS: Echocardiograms were evaluated in 55 patients (39 females, 16 males), mean age 77.0 +/- 6.9 years (range 51-90 years). The mean time of the studies was 11.0 months. The prosthesis sizes and numbers evaluated were 19 mm (n = 13), 21 mm (n = 19), 23 mm (n = 13) and 25 mm (n = 10). RESULTS: Peak aortic velocities averaged from 2.2 to 2.7 m/sec, mean gradients from 10.6 to 15.1 mmHg, peak gradients from 20.7 to 29.7 mmHg, and effective orifice area (EOA) from 1.4 to 1.8 cm (2). When accounting for the subaortic velocity, mean gradients averaged from 7.5 to 10.0 mmHg, and peak gradients averaged 15.1 to 23.5 mmHg. The effective orifice area indexes ranged from 0.8 to 1.0 cm (2)/m (2). The mean postoperative left ventricular mass index was 101.6 gm/m (2). CONCLUSIONS: The IN VIVO effective orifice areas by valve size of the Mitroflow aortic pericardial bioprosthesis provide the opportunity of avoiding obstructive characteristics for all valve sizes, including optimizing the management of the small aortic annulus.

Drinking to intracerebroventricularly infused angiotensin II, III, and IV in the SHR.

Spontaneously hypertensive rats (SHR) revealed exaggerated water consumption to the intracerebroventricular (ICV) infusion of angiotensin II (AII), and angiotensin III (AIII), as compared with Wistar-Kyoto (WKY) and Sprague-Dawley (SD) normotensive rat strains, in agreement with an earlier report (30) that employed ICV bolus injections of AII and AIII. However, the ICV infusion of AII(3-8) (AIV) did not yield reliable drinking. A second hypothesis that the infusion of AII and AIII would yield equivalent drinking within members of each strain, as previously observed with bolus ICV injections in SD rats, was not confirmed. In contrast, ICV infusion of AII yielded greater water intake than AIII in members of each strain tested. These results suggest that the slow infusion of these ligands allowed endogenous aminopeptidases to adequately keep pace with the degradation of these peptides in contrast with bolus injections that could temporarily saturate the available aminopeptidases thus extending the half-life of the ligand.

Autoradiographic identification of brain angiotensin IV binding sites and differential c-Fos expression following intracerebroventricular injection of angiotensin II and IV in rats.

A unique angiotensin binding site specific for the hexapeptide, angiotensin II(3-8) (AngIV), has been previously reported by our laboratory in the guinea pig brain and is presently described in the rat brain. This angiotensin receptor subtype has been termed AT4 and is prominently distributed in cerebral cortex, piriform cortex, hippocampus, habenulae, colliculi, septum, periaqueductal gray, several thalamic nuclei, the arcuate nucleus of the hypothalamus and cerebellum. In the second part of the present investigation, separate groups of rats received i.c.v. injections of angiotensin II (AngII), AngIV or artificial cerebrospinal fluid (aCSF) and were euthanized 2 h later for the purpose of evaluating for brain c-Fos expression. After i.c.v.-injected AngIV, Fos-like immunoreactivity was present in the hippocampus and piriform cortex. This immunoreactivity was unaffected by i.c.v. pretreatment with the AT1 angiotensin receptor antagonist DuP 753 (losartan) or the AT2 receptor ligand PD123177 but was blocked by the AT4 angiotensin receptor antagonist, divalanal-AngIV. I.c.v. injection of AngII resulted in Fos-like immunoreactivity in the dorsal third and lateral ventricles, subfornical organ, lateral hypothalamus and amygdala. Pretreatment with losartan or PD123177 significantly interfered with this AngII-induced immunoreactivity while divalanal-AngIV did not. These results indicate that in both guinea pig and rat brains the AT4 receptor has a distribution different than that previously reported for AT1 and AT2 receptor subtypes. The c-Fos expression results suggest that different brain neuronal pathways are activated by i.c.v. injection of AngII and AngIV.

Intracerebroventricularly infused [D-Arg1]angiotensin III, is superior to [D-Asp1]angiotensin II, as a pressor agent in rats.

Two D-amino acid substitution angiotensin analogues were compared against native angiotensin II (AII) and angiotensin III (AIII) for their resistance to brain tissue-induced degradation and for pressor potency when intracerebroventricularly (i.c.v.) infused in Sprague-Dawley rats. The in vitro results indicate that [D-Asp1]AII was very resistant to degradation, AII and [D-Arg1]AIII were degraded at similar rates, while AIII was the most rapidly degraded. In vivo results revealed that AII, AIII and [D-Arg1]AIII produced greater pressor responses than [D-Asp1]AII. Intracerebroventricular pretreatment with the aminopeptidase A inhibitor, amastatin, significantly reduced the subsequent pressor response to i.c.v. infused [D-Asp1]AII presumably by inhibiting its conversion to AIII. In contrast, pretreatment with the aminopeptidase B inhibitor, bestatin, potentiated the subsequent pressor response to i.c.v. infused [D-Arg1]AIII, presumably by inhibiting the conversion of [D-Arg1]AIII to the less active hexapeptide AII(3-8). Next, i.c.v. pretreatment with the specific angiotensin receptor antagonist, [Sar1, Thr8]AII (Sarthran) was found to greatly diminish the subsequent pressor responses to i.c.v. infused [D-Asp1]AII and [D-Arg1]AIII, suggesting that these analogues are having their effect at the same brain angiotensin receptor site. These results support the hypothesis that AIII, or AIII-like ligands, may serve as the active form of brain angiotensin.

Head phantoms for neutron capture therapy.

A water-filled head phantom that is designed for use in boron neutron capture therapy is described. The shape of this ellipsoidal phantom, based on the Synder head model, and its composition are designed to simulate the neutron slowing down properties of the human skull and brain. Small ion chambers or activation foils can be placed in many locations within the phantom volume. This permits accurate three-dimensional mapping of all relevant dose components and use of these dose contours for beam development as well as for benchmarking of computer-based patient treatment codes.

Hypothalamic angiotensin release in response to AII or glutamic acid stimulation of the SFO in rats.

Recent evidence from our laboratory suggests that angiotensin II (AII) is synthesized, stored within cells in the paraventricular nucleus (PVN) of the hypothalamus, and upon appropriate stimulation, released and rapidly converted to angiotensin III (AIII). The present investigation extends these observations by first employing a retrograde tracer to confirm a direct connection from the subfornical organ (SFO) to the PVN, and then showing that microinfusion of AII or glutamic acid into the SFO provokes release of endogenous angiotensin within the PVN. Potentially it is this release that contributes to the elevations in blood pressure and drinking that have been reported to occur with electrical and chemical stimulation of the SFO. These results represent the first evidence of releasable angiotensin provoked by the chemical activation of a neural pathway that has been histochemically demonstrated to link the SFO with the PVN and brain stem structures concerned with cardiovascular functioning.

Use of aminopeptidase M as a hypotensive agent in spontaneously hypertensive rats.

The present investigation determined that a commercially available aminopeptidase M (AmM, Sigma Chemical) can be utilized to lower blood pressure in normotensive and hypertensive rats. In vitro analyses indicated that the predominant peptidase present in this preparation was AmM; however, it also contained some aminopeptidase A (AmA) and less DAP IV. Although no DAP IV-mediated metabolism of angiotensin II (AII) or angiotensin III (AIII) was measured, both AmM and AmA metabolized AII and AIII. Upon further examination, it appeared that AII could be converted to AIII by either AmM or AmA; however, Arg was cleaved from the N-Terminal of AIII predominantly by AmM. The aminopeptidase inhibitors actinonin (AC), amastatin (AM), and bestatin (BE) effectively blocked the AmM-induced hydrolysis of the Asp-Arg bond of AII, and the Arg-Val bond of AIII. The activity of AmA was inhibited by AM but was relatively resistant to inhibition by AC and BE. Next, exogenous aminopeptidase replacement was employed in the anesthetized spontaneously hypertensive rat (SHR) in an attempt to temporarily correct a hypothesized brain deficiency of receptor-associated peptidases and lower blood pressure. Third-ventricle infusion of AmM produced significant drops in blood pressure and heart rate in both SHRs and Wistar-Kyoto normotensive controls. Pretreatment with AC or BE was particularly effective at interfering with the subsequent AmM-induced hypotensive effect, while AM was less effective. The central mechanisms underlying these effects are in need of further investigation; however, they are at least partially dependent upon the brain angiotensin system.

Special needs children in the public schools: perceptions of school nurses and school teachers.

Schools are faced with the challenges presented by special needs children (SNC) because the law requires that they must provide educational opportunities to all children--those who have no handicapping conditions as well as those who do, no matter how severe those conditions. The need exists for adequately prepared health care professionals in the school setting. Using a convenience sample of school teachers and school nurses, this investigation focused on the perceptions of school teachers and nurses regarding the challenges and demands of having these children in the public school. Two surveys were conducted to study those perceptions. Quantitative and qualitative data analyses showed that the needs of both groups of providers--school nurses and school teachers--can be summed up in three categories: information dissemination, communication, and resource integration. Infrastructure development involves the establishment of an effective information management system, effective use of such a system in establishing communications between all participants, and adequate administrative support to facilitate the development of the school providers' sense of competence in the care of SNC. A well-planned and adequately supported program goes a long way toward changing people's attitudes toward the inclusion of SNC in the classroom.

Placental structure and inflammation in pregnancies associated with obesity.

BACKGROUND: Pre-gravid obesity is associated with increased morbidity and mortality for both mother and offspring. Recent studies have demonstrated a heightened inflammatory response both systemically and locally within the adipose and placental tissue in women with pre-gravid obesity, which may play a role in mediating the adverse pregnancy outcomes. The aim of this study was to characterise the maternal and placental inflammatory status and investigate associated changes in placental structure in obese women. METHODS: The pro-inflammatory status of a cohort of 47 non-obese (BMI 20-25 kg/m(2)) and 33 obese (≥30 kg/m(2)) women was characterised by measuring maternal circulating levels and placental gene expression of pro-inflammatory cytokines, and quantifying immune cell populations within the placenta. The effect of pre-gravid obesity on placental structure was investigated by examining placental maturity, vessel density, the formation of syncytial knots and sprouts, and the degree of fibrin deposition, chorangiosis and muscularisation of vessel walls. RESULTS: Maternal obesity was associated with significantly greater IL-1ß (p < 0.05), IL-8 (p < 0.05), MCP-1 (p < 0.001) and CXCR2 (p < 0.05) mRNA expression within the placenta and higher circulating maternal levels of IL-6 (3.30 ± 0.38 vs. 1.77 ± 0.15 pg/ml) (p < 0.001) compared with non-obese women. There were no differences in the number of CD14(+), CD68(+) cells or neutrophils within the placental villi of non-obese and obese women. However there were significantly higher numbers of neutrophils within the interstitial space (p < 0.05). Greater muscularity of placental vessel walls was associated with maternal obesity (p = 0.03), however no other associated structural changes were observed. CONCLUSIONS: Our findings show that although pre-gravid obesity was associated with greater expression of placental pro-inflammatory cytokines and higher circulating IL-6 in pregnancy, there were no major differences in immune cell populations within the placental villi and only a greater degree of muscularity in the vessel walls.

Colloidal cutin-like substances cross-linked to siderophore decomposition products mobilizing plutonium from contaminated soils.

Relatively recently, inorganic colloids have been invoked to reconcile the apparent contradictions between expectations based on classical dissolved-phase Pu transport and field observations of "enhanced" Pu mobility (Kersting et al. Nature 1999, 397, 56-59). A new paradigm for Pu transport is mobilization and transport via biologically produced ligands. This study for the first time reports a new finding of Pu being transported, at sub-pM concentrations, by a cutin-like natural substance containing siderophore-like moieties and virtually all mobile Pu. Most likely, Pu is complexed by chelating groups derived from siderophores that are covalently bound to a backbone of cutin-derived soil degradation products, thus revealing the history of initial exposure to Pu. Features such as amphiphilicity and small size make this macromolecule an ideal collector for actinides and other metals and a vector for their dispersal. Cross-linking to the hydrophobic domains (e.g., by polysaccharides) gives this macromolecule high mobility and a means of enhancing Pu transport. This finding provides a new mechanism for Pu transport through environmental systems that would not have been predicted by Pu transport models.

Best practices in the development of clinical practice guidelines.

Clinical practice guidelines (CPGs) have been used to reduce unnecessary and undesirable variations in clinical practice. Many facilities succeed in developing and using these tools, while others conclude that they are not worth the effort. This article describes the results of a systemwide analysis of the processes a healthcare system used to plan, develop, implement, and measure CPGs after several years of experience. Extensive interviews were conducted at facilities in which the CPG program was active to determine what factors had contributed to its success or failure. The result is a series of recommendations that will facilitate CPG implementation in virtually any clinical setting.

Ibuprofen, a putative anti-cataract drug, protects the lens against cyanate and galactose.

Cataract, the major cause of blindness world-wide, may be caused partly by modification of lens proteins by carbamylation and non-enzymic glycosylation (glycation) in some patients. Aspirin has been found to protect against these modifications and to prevent cyanate-induced opacification occurring in whole rate lenses. Ibuprofen is an aspirin-like anti-inflammatory drug which appeared as a protective factor against cataract in an Oxford case-control study. The binding of cyanate, galactose and glucose 6-phosphate to lens proteins, and the effect of ibuprofen on this reaction was investigated, as was cyanate-induced opacification in whole rat lenses. Labelled metabolite was incubated with bovine lens homogenate in the presence and absence of ibuprofen, and the incorporation of label into the lens homogenate was followed. Simultaneous and preincubation experiments were performed. Intact rat lenses were incubated in culture medium with and without cyanate and ibuprofen. The phase separation temperature was noted as the temperature at which opacity first appeared on cooling. Cyanate, galactose and glucose 6-phosphate bind progressively to lens proteins. Simultaneous incubation with ibuprofen reduces cyanate and galactose binding but not glucose 6-phosphate. Ibuprofen protects against opacities due to cyanate-induced phase separation. Ibuprofen has protected against cataract in the models of cataractogenesis in this study. It appears to have a different mechanism of action from that of aspirin. These studies provide some support for the idea, based on epidemiological findings, that ibuprofen might be a useful anti-cataract drug.

GABA and bicuculline-induced blood pressure changes in spontaneously hypertensive rats.

The brain GABAergic system was previously shown to influence blood pressure (BP) maintenance in rats which may in part be accomplished by disruption of the central renin-angiotensin system (RAS). We examined the potential role of GABA in sustaining the high BP exhibited by the spontaneously hypertensive rat (SHR) model of human essential hypertension. Intracerebroventricular (i.c.v.) infusion of GABA produced decreases in BP in members of three rat strains, including Wistar-Kyoto (WKY) and Sprague-Dawley normotensive controls and SHR. The SHR were significantly more sensitive to GABA than the normotensive strains. Next, the GABA receptor antagonist bicuculline (BMI) was infused i.c.v. and produced increases in BP in members of each strain. Finally, i.c.v. pretreatment with the specific angiotensin receptor antagonist [Sar1, Thr8]AII (sarthran), blocked subsequent GABA-induced decreases in BP in members of all three strains, and there was a trend toward sarthran attenuation of BMI-induced increases in BP. These results encourage the hypothesis that the hypotensive effects produced by central application of GABA are mediated by the brain angiotensin system.

Identification of high-affinity binding sites for the hepta-beta-glucoside elicitor in membranes of the model legumes Medicago truncatula and Lotus japonicus.

Previous studies have led to the identification and characterization of specific, high-affinity binding sites for a hepta-beta-glucoside elicitor in soybean. A survey of plant species for elicitor-binding activity reveals that among the plants tested, the hepta-beta-glucoside elicitor is only recognized by plants belonging to the legume family. We have characterized in detail the glucan elicitor-binding site in the model legume Medicago truncatula Gaertn., and partially characterized the site in Lotus japonicus. These sites have characteristics that are very similar to the one in soybean, with dissociation constants of 4.7 and 8.9 nM respectively. The elicitor-binding sites from both plants are stable during solubilization with non-ionic alkylglycoside detergents. However, differences are observed in the abundance of the binding sites and their selectivity towards structurally related analogues of the hepta-beta-glucoside elicitor. Our results suggest that similar, but perhaps not identical, binding sites for the hepta-beta-glucoside elicitor exist in diverse legumes, but not in plants outside of the legume family.

Nitric oxide mediates LDL uptake in the artery wall in response to high concentrations of 17 beta-estradiol.

Female sex hormones are known to affect lipoprotein flux in the artery wall and atherosclerosis. However, the mechanisms of these artery wall effects are unclear. To examine the effect of 17 beta-estradiol (estradiol) on LDL uptake in the artery wall, we developed an isolated perfused rat carotid artery model from ovariectomized rats. LDL flux in the artery wall was measured by quantitative fluorescence microscopy before and after treatment with estradiol (0.001 to 10,000 nmol/L). Dose-response experiments showed no significant difference in the rate of LDL uptake when arteries were perfused with estradiol at physiological concentrations (0.001 to 1 nmol/L) compared with control perfusions. However, higher concentrations of estradiol (10 to 10,000 nmol/L) significantly increased the rate of LDL uptake in isolated arteries. Artery lumen volume significantly increased with perfusion of estradiol (1 to 100 nmol/L) but decreased after perfusions of higher concentrations of estradiol (1000 to 10,000 nmol/L). Additional studies were performed to examine mechanisms of estradiol-mediated increases in LDL uptake. The effect of estradiol (10 nmol/L) on the rate of LDL uptake was blocked by nitric oxide synthase inhibitors. However, the estrogen receptor antagonist tamoxifen did not block the effects of estradiol on the rate of LDL uptake. Our study indicates that modulation of LDL uptake in the artery wall by estradiol is concentration dependent. High concentrations of estradiol increase LDL uptake by production of endothelium-derived nitric oxide. These observations suggest that increased nitric oxide production compromises endothelial layer barrier function to increase LDL uptake in the artery wall.

Effect of environmental tobacco smoke on LDL accumulation in the artery wall.

BACKGROUND: Previous research has shown that exposure to environmental tobacco smoke (ETS) increases the risk of atherosclerosis. To test the hypothesis that exposure to ETS increases LDL accumulation in the artery wall, we developed a model to measure the rate of LDL accumulation in individually perfused rat carotid arteries after the artery had been perfused with plasma taken from rats exposed to ETS (ETS-plasma). METHODS AND RESULTS: Rats were exposed to ETS in a chamber in which steady-state sidestream smoke was continuously circulating. After exposure, blood from the animals was collected. Carotid arteries from unexposed rats were perfused first with normal plasma containing fluorescently labeled LDL. Then the same arteries (10 arteries from five rats) were perfused with ETS-plasma plus fluorescently labeled LDL. Photometric measurements were made during perfusion of the arteries with fluorescently labeled LDL, and rate of LDL accumulation (mV/min) and lumen volume (mV) (volume of fluorescently labeled LDL solution) were determined. Perfusion with ETS-plasma increased the rate of LDL accumulation (mean +/- SEM, 6.9 +/- 1.8 mV/min) compared with control (1.6 +/- 0.40 mV/min, P < or = .02). LDL accumulation was primarily dependent on LDL interaction with ETS-plasma rather than the interaction of ETS-plasma with the artery wall. Also, ETS-plasma significantly increased lumen volume (43.3 +/- 5.1 mV) compared with control (35.1 +/- 4.4 mV, P < or = .005). CONCLUSIONS: Exposure to ETS acutely increased LDL accumulation in perfused arteries. Repeated exposure to ETS may represent important early events in atherogenesis.