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At least 955 records · Page 53Linked to original sources
PubMed2004

Black tea increases coronary flow velocity reserve in healthy male subjects.

Epidemiologic studies suggest that tea consumption decreases the risk for cardiovascular events. However, there has been no clinical report examining the effects of tea consumption on coronary circulation. The purpose of this study was to evaluate the effects of black tea on coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). This was a double-blind crossover study of 10 healthy male volunteers conducted to compare the effects of black tea and caffeine on coronary circulation. The coronary flow velocity of the left anterior descending coronary artery was measured at baseline and at hyperemia during adenosine triphosphate infusion by TTDE to determine CFVR. The CFVR ratio was defined as the ratio of CFVR after beverage consumption to CFVR before beverage consumption. All data were divided into 2 groups according to beverage type: group T (black tea) and group C (caffeine). Two-way analysis of variance showed a significant group effect and interaction in CFVR before and after beverage consumption (p = 0.001). CFVR significantly increased after tea consumption in group T (4.5 +/- 0.9 vs 5.2 +/- 0.9, p <0.0001). The CFVR ratio of group T was larger than that of group C (1.18 +/- 0.07 vs 1.04 +/- 0.08, p = 0.002). Acute black tea consumption improves coronary vessel function, as determined by CFVR.

Adult↗
PubMed2005

BIBN4096BS antagonizes human alpha-calcitonin gene related peptide-induced headache and extracerebral artery dilatation.

BACKGROUND AND OBJECTIVE: Calcitonin gene-related peptide (CGRP) plays a pivotal role in migraine pathogenesis. BIBN4096BS is the first CGRP receptor antagonist available for human studies, and its efficacy in the acute treatment of migraine has been demonstrated. We investigated the ability of BIBN4096BS to inhibit human alphaCGRP (h-alphaCGRP)-induced headache and cerebral hemodynamic changes in healthy volunteers. METHODS: Ten healthy volunteers completed this double-blind, placebo-controlled crossover study with 2.5 mg BIBN4096BS and placebo as pretreatments before a 20-minute intravenous infusion of h-alphaCGRP (1.5 microg/min). Transcranial Doppler ultrasonography was used to measure blood flow velocity in the middle cerebral artery (MCA); regional and global cerebral blood flow (CBF) was measured by xenon 133 inhalation single-photon emission computed tomography. The temporal and radial artery diameter was measured by high-frequency ultrasound. Systemic hemodynamics, end-tidal partial pressure of carbon dioxide (PETCO(2)), and headache were monitored. RESULTS: Of the 10 volunteers, 6 had a CGRP-induced headache during the in-hospital phase after placebo pretreatment but none after BIBN4096BS (P = .031). BIBN4096BS did not affect changes in the diameter of the MCA or changes in CBF induced by h-alphaCGRP. Vasodilatation of the extracranial arteries was, however, significantly inhibited (P < .001 for temporal artery and P = .001 for radial artery). CONCLUSIONS: These results show that BIBN4096BS effectively prevents CGRP-induced headache and extracerebral vasodilatation but does not significantly affect the induced cerebral hemodynamic changes.

Adult↗
PubMed2005

High-dose folic acid acutely improves coronary vasodilator function in patients with coronary artery disease.

OBJECTIVES: We investigated the acute effect of orally administered high-dose folic acid on coronary dilator function in humans. BACKGROUND: Folic acid and its active metabolite, 5-methyltetrahydrofolate, increase endothelium-dependent vasodilation in human peripheral circulation. However, the acute effect on coronary circulation is not known. METHODS: Fourteen patients with ischemic heart disease, age 62 +/- 12 years (mean +/- SD), were enrolled in a double-blind, placebo-controlled crossover trial. Basal and adenosine-stimulated myocardial blood flow (MBF) were determined by positron emission tomography, and myocardial flow reserve was calculated. Each patient was studied after ingestion of placebo and after ingestion of 30 mg folic acid. Myocardial zones were prospectively defined physiologically as "normal" versus "abnormal" on the basis of MBF response to adenosine 140 microg/kg/min (normal = MBF >1.65 ml/min/g). Abnormal and normal zones were analyzed separately in a patient-based analysis. RESULTS: Folate was associated with a reduction in mean arterial pressure (100 +/- 12 mm Hg vs. 96 +/- 11 mm Hg, placebo vs. folate, p < 0.03). Despite the fall in mean arterial pressure, folic acid significantly increased the MBF dose response to adenosine (p < 0.001 using analysis of variance) in abnormal zones, whereas MBF in normal zones did not change. In abnormal segments, folic acid increased peak MBF by 49% (1.45 +/- 0.59 ml/min/g vs. 2.16 +/- 1.01 ml/min/g, p < 0.02). Furthermore, folate increased dilator reserve by 83% in abnormal segments (0.77 +/- 0.59 vs. ml/min/g 1.41 +/- 1.08 ml/min/g, placebo vs. folate, p < 0.05), whereas dilator reserve in normal segments remained unchanged (2.00 +/- 0.61 ml/min/g vs. 2.12 +/- 0.69 ml/min/g, placebo vs. folate, p = NS). CONCLUSIONS: The data demonstrate that high-dose oral folate acutely lowers blood pressure and enhances coronary dilation in patients with coronary artery disease.

Adenosine↗
PubMed2005

Effect of Aerodiol administration on cerebral blood flow volume in postmenopausal women.

OBJECTIVE: The aim of the study was to evaluate the acute effect of the intranasal 17beta-estradiol (Aerodiol, Servier, Chambray-les-Tours, France) administration on cerebral blood flow (CBF) volume. METHODS: Eighteen healthy women who had been natural postmenopausal for at least 1 year were enrolled in the study. We conducted an experimental, randomized, placebo-controlled, crossover, double-blinded study of the acute effect of 17beta-estradiol on the internal carotid artery (ICA), vertebral artery (VA) and, CBF volume using color duplex sonography. RESULTS: There were significant increases in the ICA, VA flow volumes and CBF volume after 17beta-estradiol administration compared to placebo measurements. However, there was no statistically significant difference in flow velocities or pulsatility indices. CONCLUSION: Nasal 17beta-estradiol administration in postmenopausal women causes significant increases in CBF volume due to its vasodilatatory effect on ICA and VA.

Administration, Intranasal↗
PubMed2005

Computer analysis of three-dimensional power angiography images of foetal cerebral, lung and placental circulation in normal and high-risk pregnancy.

Three-dimensional (3-D) ultrasound (US) has greatly improved evaluation of organ circulation. The aim of this study was to explore the possible use of this new technique in normal and high-risk pregnancies. Fetal brain, lung and placenta 3-D power Doppler signal intensity were recorded in 115 normal singleton pregnancies (24 to 42 weeks gestation) and in 67 high-risk pregnancies. Mean image pixel signal intensity was calculated for each organ and a brain-lung ratio. In normal pregnancy, placental and lung signal intensity increased until 33, with a rapid decrease after 38, weeks of gestation. Fetal cerebral signal intensity increased with gestational age. Placental and fetal lung signal intensity was significantly lower in high-risk pregnancies than in the control group, with increased fetal brain and brain-lung ratios. The present results suggest a reduction of placental perfusion after 38 weeks of gestation in normal pregnancy, with redistribution of fetal circulation. Lung signal intensity increased abruptly at 32 weeks of gestation, which might reflect lung maturity. The new method showed signs of centralization of fetal circulation at the end of gestation. The results might suggest a possible clinical use for fetal surveillance in high-risk pregnancies.

Brain↗
PubMed2005

A ubiquitin-based assay for the cytosolic uptake of protein transduction domains.

Protein transduction domains (PTDs) are promising tools for transducing presynthesized polypeptides across the plasma membrane. However, the development and optimization of PTDs are hampered by many technical problems and artifacts resulting notably from the tight binding of PTDs to the cell surface and the difficulty in discriminating, through imagery analyses, truly cytosolic from cytoplasmic vesicular compartments. To circumvent these problems, we have developed an unambiguous enzymatic assay of the cytosolic uptake of PTD-driven proteins, based on the processing by ubiquitin-specific C-terminal proteases (DUBs). This method, coupled with fluorometry and fluorescence microscopy, shows that the TAT PTD derived from human immunodeficiency virus type 1 is rapidly taken up by cells but fails to reach their cytosol, except when dendritic cells, which are known to take up circulating antigens for cross-presentation, are used. In addition to its usefulness in assessing cytosolic uptake, DUB processing of PTD-linked proteins can ensure the intracellular release of cargo proteins, which might prove helpful for MHC-I-based vaccination or intracellular delivery of biologically active polypeptides.

Animals↗
PubMed1996

Transplacental passage of recombinant human granulocyte colony-stimulating factor in women with an imminent preterm delivery.

OBJECTIVE: We attempted to determine, in a pilot study, whether recombinant human granulocyte colony-stimulating factor, administered to women with an imminent delivery at < or = 30 weeks' estimated gestational age, crosses to the fetal circulation and stimulates fetal neutrophil production. STUDY DESIGN: We measured granulocyte colony-stimulating factor and neutrophil concentrations in the blood of the mothers and in the umbilical venous cord blood after a single intravenous dose (25 micrograms/kg) of recombinant granulocyte colony-stimulating factor given to 11 women in whom preterm delivery was imminent and compared these with values from 34 control women and 35 cord sera. RESULTS: Ten infants were delivered within 30 hours (10.8 +/- 8.9, mean +/- SD) of the granulocyte colony-stimulating factor administration ("early delivery"), and two were delivered after 54 and 108 hours, respectively. In the early delivery group maternal granulocyte colony-stimulating factor concentrations and blood neutrophil levels were higher than in controls. However, no difference was seen in the cord blood neutrophil concentrations. In the late delivery group, although maternal serum and cord blood granulocyte colony-stimulating factor concentrations did not differ from controls, cord blood neutrophil levels were higher (25,900 and 17,700 cells/microliters) than controls (3500 +/- 2000 cells/microliters, p < 0.05) and remained elevated for 1 week. Specifically, the blood neutrophil levels on days 5 and 8 were 12,000 and 17,000, respectively, for these patients, whereas the reference range upper limit for controls was 6000 cells/microliters. CONCLUSION: Administration of recombinant granulocyte colony-stimulating factor to pregnant women with an imminent preterm delivery may result in the transplacental passage of a measurable quantity of granulocyte colony-stimulating factor, an amount that can have a biologic effect on the fetus. These events were most noticeable in those patients who received granulocyte colony-stimulating factor at least 30 hours before being delivered of their infants.

Bacterial Infections↗
PubMed2000

Opposite effects of high and low frequency rTMS on regional brain activity in depressed patients.

BACKGROUND: High (10-20 Hz) and low frequency (1-5 Hz) repetitive transcranial magnetic stimulation (rTMS) have been explored for possible therapeutic effects in the treatment of neuropsychiatric disorders. As part of a double-blind, placebo-controlled, crossover study evaluating the antidepressant effect of daily rTMS over the left prefrontal cortex, we evaluated changes in absolute regional cerebral blood flow (rCBF) after treatment with 1- and 20-Hz rTMS. Based on preclinical data, we postulated that high frequency rTMS would increase and low frequency rTMS would decrease flow in frontal and related subcortical circuits. METHODS: Ten medication-free, adult patients with major depression (eight unipolar and two bipolar) were serially imaged using (15)O water and positron emission tomography to measure rCBF. Each patient was scanned at baseline and 72 hours after 10 daily treatments with 20-Hz rTMS and 10 daily treatments with 1 Hz rTMS given in a randomized order. TMS was administered over the left prefrontal cortex at 100% of motor threshold (MT). Significant changes in rCBF from pretreatment baseline were determined by paired t test. RESULTS: Twenty-hertz rTMS over the left prefrontal cortex was associated only with increases in rCBF. Significant increases in rCBF across the group of all 10 patients were located in the prefrontal cortex (L > R), the cingulate gyrus (L >> R), and the left amygdala, as well as bilateral insula, basal ganglia, uncus, hippocampus, parahippocampus, thalamus, and cerebellum. In contrast, 1-Hz rTMS was associated only with decreases in rCBF. Significant decreases in flow were noted in small areas of the right prefrontal cortex, left medial temporal cortex, left basal ganglia, and left amygdala. The changes in mood following the two rTMS frequencies were inversely related (r = -.78, p <.005, n = 10) such that individuals who improved with one frequency worsened with the other. CONCLUSIONS: These data indicate that 2 weeks of daily 20-Hz rTMS over the left prefrontal cortex at 100% MT induce persistent increases in rCBF in bilateral frontal, limbic, and paralimbic regions implicated in depression, whereas 1-Hz rTMS produces more circumscribed decreases (including in the left amygdala). These data demonstrate frequency-dependent, opposite effects of high and low frequency rTMS on local and distant regional brain activity that may have important implications for clinical therapeutics in various neuropsychiatric disorders.

Adult↗
PubMed1997

The relation between pump flow rate and pulsatility on cerebral hemodynamics during pediatric cardiopulmonary bypass.

OBJECTIVES: Neurologic impairment, at least partly ischemic in origin, has been reported in up to 25% of infants undergoing cardiopulmonary bypass, with or without circulatory arrest. Controversy continues about the effect of pump flow, pulsatile or nonpulsatile, on the brain and in particular on cerebral blood flow. This study examines the relationship between pump flow rate and cerebral hemodynamics during pulsatile and nonpulsatile cardiopulmonary bypass. METHOD: Near-infrared spectroscopy was used to determine cerebral blood flow and cerebral blood volume (measured as concentration change) in a randomized crossover study. Pulsatile and nonpulsatile flow were used for six 5-minute intervals at each of three different pump flow rates (0.6, 1.2, and 2.4 L x m2 x min(-1)) in 40 patients, median age 2 months (range 2 weeks to 20 years 5 months). The relations between pulsatile flow, pump flow rate, cerebral blood flow, hemoglobin concentration change (cerebral blood volume), mean arterial pressure, arterial carbon dioxide tension, and hematocrit value were prospectively examined by means of multivariate analysis. RESULTS: Cerebral blood flow decreased 36% per L x m(-2) x min(-1) decrease in pump flow rate and was associated with changes in mean arterial pressure but did not differ according to pulsatility. Change in hemoglobin concentration was unrelated to changes in pulsatility of pump flow. CONCLUSION: Cerebral blood flow is related to pump flow rate. Pulsatile flow delivered with a Stöckert pump does not increase cerebral blood flow or alter hemoglobin concentration during cardiopulmonary bypass in children.

Blood Volume↗
PubMed2002

Homocysteine impairs coronary microvascular dilator function in humans.

OBJECTIVES: We sought to use positron emission tomography (PET) to test the hypothesis that hyperhomocysteinemia adversely effects coronary microvascular dilator function. BACKGROUND: Hyperhomocysteinemia is associated with abnormal endothelium-dependent vasodilation in peripheral human arteries. However, its effect on the coronary circulation is not known. METHODS: Eighteen healthy humans, age 24 to 56 years, were enrolled in a double-blind, crossover trial. Basal and adenosine-stimulated myocardial blood flow (MBF) was determined by PET: after ingestion of placebo and after methionine-induced hyperhomocysteinemia. Further, brachial ultrasonography was used to assess flow-mediated vasodilation. Additionally, to assess the role of nitric oxide (NO) in adenosine-mediated vasodilation, the MBF response to adenosine was measured in the presence and absence of the NO synthase antagonist NG-monomethyl-l-arginine (l-NMMA) (0.3 mg/kg/min intravenously). RESULTS: Hyperhomocysteinemia resulted in a reduction in the MBF dose-response curve to adenosine (p < 0.05). This was most apparent with low dose adenosine, where MBF augmentation was significantly blunted during hyperhomocysteinemia (1.06 +/- 1.00 ml/min/g vs. 0.58 +/- 0.78 ml/min/g, placebo vs. methionine, p < 0.05). Similarly, flow-mediated brachial artery vasodilation was impaired during hyperhomocysteinemia (4.4 +/- 2.6% vs. 2.6 +/- 2.3%, placebo vs. methionine, p < 0.05). In a separate series of experiments, MBF during adenosine was reduced in the presence of l-NMMA (p < 0.05 analysis of variance). This was most apparent at the low dose of adenosine, where MBF response to adenosine was blunted in the presence of l-NMMA (2.08 +/- 1.34 ml/min/g vs. 1.48 +/- 1.32 ml/min/g, placebo vs. l-NMMA, p < 0.05). CONCLUSION: The data, therefore, support the hypothesis that acute hyperhomocysteinemia impairs microvascular dilation in the human coronary circulation as a result of reduced NO bioavailability.

Adenosine↗
PubMed2002

Plasma asymmetric dimethylarginine and hyperemic myocardial blood flow in young subjects with borderline hypertension or familial hypercholesterolemia.

OBJECTIVE: The goal of this study was to examine the relationship between plasma asymmetric dimethylarginine (ADMA) level and hyperemic myocardial blood flow (MBF) in subjects with borderline hypertension (BHT) and familial hypercholesterolemia (FH). METHODS: Asymmetric dimethylarginine is an endogenous competitive inhibitor of nitric oxide synthase that may modulate vascular function. We measured plasma ADMA levels and myocardial flow in 77 young men (mean age 35 +/- 5 years), including 47 healthy controls, 16 men with BHT, and 14 men with FH. Basal and dipyridamole-induced myocardial flow was measured using positron emission tomography. Plasma ADMA levels were measured using high-pressure liquid chromatography. RESULTS: Asymmetric dimethylarginine levels were significantly elevated in the BHT group compared with controls (0.59 +/- 0.13 micromol/l vs. 0.43 +/- 0.12 micromol/l, p < 0.001), and they had significantly lower dipyridamole flow (2.85 +/- 1.20 ml/min/g vs. 3.69 +/- 1.68 ml/min/g, p < 0.05). In a multivariate regression model adjusted for the study group, dipyridamole flow was inversely associated with ADMA (p < 0.05), age (p < 0.05), and apolipoprotein B concentration (p < 0.05). CONCLUSIONS: We conclude that plasma ADMA concentration is related to dipyridamole-induced vasodilatory function in young men, independently of blood pressure elevation and hypercholesterolemia. Subjects with BHT have significantly increased plasma ADMA levels, which may partly explain the impaired hyperemic MBF in this condition.

Adult↗
PubMed2003

Echocardiographic predictors of aortopulmonary collaterals in infants with tetralogy of fallot and pulmonary atresia.

OBJECTIVES: This study was designed to identify echocardiographic predictors of aortopulmonary collaterals (APCs) in infants with tetralogy of Fallot and pulmonary atresia (TOF/PA) and to prospectively validate these predictors. BACKGROUND: In patients with TOF/PA, routine preoperative diagnostic cardiac catheterization is usually performed to determine the presence and distribution of APCs and the anatomy of the branch pulmonary arteries. METHODS: The clinical and diagnostic imaging data of infants with TOF/PA treated between 1990 and 2000 were reviewed. Patients were classified into two groups based on cineangiographic findings: 1) no APCs (n = 34), and 2) >or=1 APCs (n = 59). Echocardiographic variables were examined for their ability to identify patients having >or=1 APCs. RESULTS: Median branch pulmonary artery diameter Z scores were significantly larger in patients without APCs compared with those having >or=1 APCs: -0.56 versus -3.24 for the left pulmonary artery and -0.76 versus -3.46 for the right pulmonary artery (p < 0.001). The presence of a branch pulmonary artery diameter Z score or=1 APCs. Detection of APCs by color Doppler was 93% sensitive and 91% specific. A combination of branch pulmonary artery diameter Z score or=1 APCs. The diagnostic accuracy of these echocardiographic variables was subsequently validated in a prospective study of 11 infants. CONCLUSIONS: Echocardiography is a sensitive and specific test for the detection of >or=1 APCs in infants with TOF/PA. These data can be used to select patients who can undergo complete repair of TOF/PA without further preoperative diagnostic imaging.

Aorta, Thoracic↗
PubMed2003

Effect of sildenafil (Viagra) on cerebral blood flow velocity: a pilot study.

Sildenafil (Viagra) is a selective inhibitor of the cyclic guanosine monophosphate (cGMP) specific phosphodiesterase 5 (PDE5) used for the oral treatment of male erectile dysfunction due to vasodilation. However, assessment of direct effects of sildenafil on cerebral arteries is unknown. The aim of this present experiment is to measure the possible changes in blood flow velocity of the middle cerebral artery after the administration of sildenafil and a placebo. Blood-flow velocity changes of the middle cerebral artery were measured before and 1 to 2 h after the administration of the drug. Neither the intake of sildenafil nor the application of placebo resulted in any significant changes in blood flow velocity of the right middle cerebral artery. The next step for future experiments will be in vitro measurement of the diameters of the cerebral arteries under the influence of sildenafil and in vivo measurement of carbon dioxide and cerebral blood flow velocity during sexual stimulation after sildenafil intake instead of under resting conditions.

Adult↗
PubMed2004

Interleaved transcranial magnetic stimulation/functional MRI confirms that lamotrigine inhibits cortical excitability in healthy young men.

Little is known about how lamotrigine (LTG) works within brain circuits to achieve its clinical effects. We wished to determine whether the new technique of interleaved transcranial magnetic stimulation (TMS)/functional magnetic resonance imaging (fMRI) could be used to assess the effects of LTG on activated motor or prefrontal/limbic circuits. We carried out a randomized, double-blind, crossover trial involving two visits 1 week apart with TMS measures of cortical excitability and blood oxygen level-dependent TMS/fMRI. Subjects received either a single oral dose of 325 mg of LTG or placebo on each visit. In all, 10 subjects provided a complete data set that included interleaved TMS/fMRI measures and resting motor threshold (rMT) determinations under both placebo and LTG conditions. A further two subjects provided only rMT data under the two drug conditions. LTG caused a 14.9+/-9.6% (mean+/-SD) increase in rMT 3 h after the drug, compared with a 0.6+/-10.9% increase 3 h after placebo (t=3.41, df =11, p<0.01). fMRI scans showed that LTG diffusely inhibited cortical activation induced by TMS applied over the motor cortex. In contrast, when TMS was applied over the prefrontal cortex, LTG increased the TMS-induced activation of limbic regions, notably the orbitofrontal cortex and hippocampus. These results suggest that LTG, at clinically relevant serum concentrations, has a general inhibitory effect on cortical neuronal excitability, but may have a more complex effect on limbic circuits. Furthermore, the interleaved TMS/fMRI technique may be a useful tool for investigating regional brain effects of psychoactive compounds.

Adolescent↗
PubMed2002

Effect of xenon on cerebral autoregulation in pigs.

There are little data on the effect of anaesthetic concentrations of xenon on cerebral pressure autoregulation. In this study, we have investigated the effect of 79% xenon inhalation on cerebral pressure autoregulation and CO2 response in pigs. Ten pigs were randomly allocated to receive xenon 79% or halothane anaesthesia, respectively, in a crossover designed study. Halothane was used to validate the experimental set-up. Transcranial Doppler was performed to determine the mean flow velocities in the middle cerebral artery (vMCA) during defined cerebral perfusion pressures and during normo-, hyper- and hypoventilation. The results showed that the inhalation of 79% xenon preserved cerebral autoregulation during conditions of normo-, hyper- and hypoventilation and at different cerebral perfusion pressures in pigs. These results suggest that with the inhalation of xenon, in the highest concentration suitable for a safe clinical use, cerebral autoregulation is preserved.

Anesthetics, Inhalation↗
PubMed2000

Identification of Escherichia coli K1 genes contributing to human brain microvascular endothelial cell invasion by differential fluorescence induction.

Most cases of Escherichia coli K1 meningitis arise as a result of haematogenous spread, however there is a limited understanding of the mechanisms by which circulating E. coli K1 cross the blood-brain barrier. We have previously shown that environmental growth conditions both positively and negatively influence the capabilities of E. coli K1 to invade brain microvascular endothelial cells (BMEC), for example growth in media supplemented with 50% newborn bovine serum (NBS) increased BMEC invasion, whereas growth in media supplemented with 0.2 M NaCl repressed invasion in vitro and in vivo. In this study, differential fluorescence induction (DFI) was used to identify E. coli K1 genes involved in this differentially expressed invasion phenotype. E. coli K1 promoter libraries were constructed and screened for gfp expression in a manner analogous to the above growth conditions. Twenty-four clones were isolated that showed fluorescence induction when grown under the invasion-enhancing condition (i.e. NBS). Four of these clones also demonstrated repression or no induction of fluorescence when grown under the invasion-repressing condition (i.e. 0.2 M NaCl). One such clone, containing a ygdP promoter and an open reading frame (ORF), showed significant homology to Bartonella bacilliformis IalA (invasion associated locus). Among the other NBS-inducing loci, finPtraJ was identified as well as several clones with no homology to other known genes. When ygdP, finPtraJ and several of the unique loci were disrupted in E. coli K1, there was a significant decrease in human BMEC (HBMEC) invasion. RNA transcript analysis determined that these newly identified invasion loci were differentially regulated at the transcriptional level. This is the first demonstration of using DFI to identify E. coli K1 genes contributing to HBMEC invasion.

Brain↗
PubMed2003

The effect of nitric oxide synthase inhibition on histamine induced headache and arterial dilatation in migraineurs.

We have previously proposed that histamine causes migraine via increased NO production. To test this hypothesis, we here examined if the NOS inhibitor, L-NG methylarginine hydrochloride (L-NMMA:546C88), could block or attenuate histamine induced migraine attacks and responses of the middle cerebral, temporal and radial arteries. In a double blind crossover design 12 patients were randomized to receive pretreatment with L-NMMA (6 mg/kg) or placebo i.v. over 15 min followed on both study days by histamine (0.5 microg/kg/min) i.v. for 20 min. Headache scores, mean maximal blood velocity (Vmean) in the middle cerebral artery (MCA) (transcranial doppler) and diameters of temporal and radial arteries (high resolution ultrasound) were repeatedly measured. Pre-treatment with L-NMMA, had no effect on histamine induced headache or migraine, but also had no effect on the magnitude of histamine induced-decrease in MCA blood velocity, or dilatation of neither the temporal nor the radial artery. L-NMMA constricted the temporal artery by 8% before histamine infusion, whereas the radial artery was unaffected. The temporal artery dilated 4-5 times more than the radial artery during histamine infusion. In conclusion the use of a NOS inhibitor in the highest possible dose did not block the histamine-induced headache response or arterial dilatation. Either the concentration of L-NMMA reaching the smooth muscle cell was insufficient or, histamine dilates arteries and causes headache via NO independent mechanisms. Our results showed for the first time a craniospecificity for the vasodilating effect of histamine and for the arterial effects of NOS inhibition.

Adult↗
PubMed1997

The effect of behavioural states on cerebral oxygenation during endotracheal suctioning of preterm babies.

Near infrared spectroscopy (NIRS) was used to investigate the effect of behavioural states on changes of oxygenated (O2Hb), deoxygenated haemoglobin (HHb) and total haemoglobin (tHb), during endotracheal suctioning. In an open prospective design, NIRS measurements have been done during 20 suctioning episodes in 13 preterm neonates. Heart rate, arterial oxygen saturation, and carbon dioxide tension were monitored continuously. Behavioural state (BS) observations were made and documented as well. The statistical analysis showed that in patients who were active, with crying periods during suctioning (behavioural states 4-5), changes of oxygenated (p < 0.005) and deoxygenated haemoglobin (p < 0.05), as well as of arterial oxygen saturation (p < 0.05) and heart rate (p < 0.05) were significantly greater than in patients who were quiet with predominant behavioural state 1, 2 and 3. These results underline the influence of behavioural states on the physiological answers to endotracheal suctioning. NIRS proved to be a valuable tool to evaluate possible harmful effects of different suctioning techniques.

Cerebrovascular Circulation↗