bluuebunny/crossref_metadata_2025 huggingface dataset:
Daily Nighttime Melatonin Reduces Blood Pressure in Male Patients With Essential Hypertension
Authors: Scheer Frank A.J.L. , Van Montfrans Gert A. , van Someren Eus J.W. , Mairuhu Gideon , Buijs Ruud M.
Published: January 2004

Patients with essential hypertension have disturbed autonomic cardiovascular regulation and circadian pacemaker function. Recently, the biological clock was shown to be involved in autonomic cardiovascular regulation. Our objective was to determine whether enhancement of the functioning of the biological clock by repeated nighttime melatonin intake might reduce ambulatory blood pressure in patients with essential hypertension. We conducted a randomized, double-blind, placebo-controlled, crossover trial in 16 men with untreated essential hypertension to investigate the influence of acute (single) and repeated (daily for 3 weeks) oral melatonin (2.5 mg) intake 1 hour before sleep on 24-hour ambulatory blood pressure and actigraphic estimates of sleep quality. Repeated melatonin intake reduced systolic and diastolic blood pressure during sleep by 6 and 4 mm Hg, respectively. The treatment did not affect heart rate. The day–night amplitudes of the rhythms in systolic and diastolic blood pressures were increased by 15% and 25%, respectively. A single dose of melatonin had no effect on blood pressure. Repeated (but not acute) melatonin also improved sleep. Improvements in blood pressure and sleep were statistically unrelated. In patients with essential hypertension, repeated bedtime melatonin intake significantly reduced nocturnal blood pressure. Future studies in larger patient group should be performed to define the characteristics of the patients who would benefit most from melatonin intake. The present study suggests that support of circadian pacemaker function may provide a new strategy in the treatment of essential hypertension.
Aberrant D
1
and D
3
Dopamine Receptor Transregulation in Hypertension
Authors: Zeng Chunyu , Wang Dan , Asico Laureano D. , Welch William J. , Wilcox Christopher S. , Hopfer Ulrich , Eisner Gilbert M. , Felder Robin A. , Jose Pedro A.
Published: January 2004

Dopamine plays a role in the regulation of blood pressure by inhibition of sodium transport in renal proximal tubules (RPTs) and relaxation of vascular smooth muscles. Because dopamine receptors can regulate and interact with each other, we studied the interaction of D
1
and D
3
receptors in immortalized RPT cells and mesenteric arteries from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs), and in human coronary artery smooth muscle cells (CASMCs). In WKY rats, the D
1
-like agonist, fenoldopam, increased D
3
receptor protein in a time-dependent and concentration-dependent manner (EC
50
=4.5×10
−9
M, t
1/2
=15.8 hours). In SHRs, fenoldopam (10
−5
M) actually decreased the expression of D
3
receptors. D
1
and D
3
receptor co-immunoprecipitation was increased by fenoldopam (10
−7
M/24 h) in WKY rats but not in SHRs. The effects of fenoldopam in CASMCs were similar as those in WKY RPT cells (ie, fenoldopam increased D
1
and D
3
receptor proteins). Both D
3
(PD128907, Emax=80%±6%, pED
50
=5±0.1) and D
1
-like receptor (fenoldopam, Emax=81%±8%, pED
50
=5±0.2, n=12) agonists relaxed mesenteric arterial rings. Co-stimulation of D
1
and D
3
receptors led to additive vasorelaxation in WKY rats, but not in SHRs. D
1
and D
3
receptors interact differently in WKY and SHRs. Altered interactions between D
1
and D
3
receptors may play a role in the pathogenesis of genetic hypertension, including human hypertension, because these receptors also interact in human vascular smooth muscle cells.
Rho/Rho-Kinase Pathway in the Brainstem Contributes to Hypertension Caused by Chronic Nitric Oxide Synthase Inhibition
Authors: Ito Koji , Hirooka Yoshitaka , Kishi Takuya , Kimura Yoshikuni , Kaibuchi Kozo , Shimokawa Hiroaki , Takeshita Akira
Published: January 2004

Central nervous system mechanisms are involved in hypertension caused by chronic inhibition of nitric oxide (NO) synthesis. Chronic inhibition of NO synthesis might also activate the Rho/Rho-kinase pathway in the vasculature. We recently demonstrated that activation of the Rho/Rho-kinase pathway in the nucleus tractus solitarii (NTS) contributes to hypertensive mechanisms in spontaneously hypertensive rats. The aim of the present study was to determine whether activation of this pathway also contributes to neurogenic hypertensive mechanisms caused by chronic NO synthesis inhibition. The NO synthase inhibitor
N
ω
-nitro-
l
-arginine methyl ester (
l
-NAME) was administered to Wistar-Kyoto rats in their drinking water (1 mg/mL) for 2 weeks. Bilateral microinjection of Y-27632, a specific Rho-kinase inhibitor, into the NTS elicited decreases in arterial pressure, heart rate, and renal sympathetic nerve activity in control rats and
l
-NAME–treated rats. The magnitude of the decrease, however, was significantly greater in
l
-NAME–treated than in control rats. In another group of rats, the specific Rho-kinase inhibitor, Y-27632, was administered intracisternally for 2 weeks with a mini-osmotic pump from the beginning of treatment with
l
-NAME. Y-27632 co-treatment significantly attenuated the increase in arterial pressure. Furthermore, the expression level of membranous RhoA and phosphorylation of the target proteins of Rho-kinase, the ERM (ezrin, radixin, moesin) family members, was significantly greater in
l
-NAME–treated rats than in control rats. These results indicate that activation of the Rho/Rho-kinase pathway in the NTS contributes to neurogenic hypertension caused by chronic NO synthase inhibition.
Guidelines for Hypertension: Are Quality-Assurance Measures on Target?
Authors: Singer Gregory M. , Izhar Munavvar , Black Henry R.
Published: January 2004

Guideline committees recommend targets of treatment based on trial data on efficacy and effectiveness. Quality-assurance initiatives apply these parameters in the general practice setting. Therefore, targets must be feasible and achievable by the practicing physicians who are judged by these targets as goals for care. We evaluated 437 patients in the Rush University Hypertension Clinic using the Health Employer Data Information Set (HEDIS) measures for 2000 to assess goal achievement in a practice-based setting. We compared guideline achievement of uncomplicated hypertensive and diabetic subjects to standards dictated by HEDIS, the 6th Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI), and the American Diabetic Association (ADA)/National Kidney Foundation (NKF). Overall, 276 (63%) patients achieved SBP goal, with 376 (86%) achieving DBP goal and 358 (59%) achieving both goals. However, in the 20% of patients who were diabetic, only 52% had a BP of <140 mm Hg and <90 mm Hg, whereas only 22% achieved the more stringent goals of JNC VI of <130 mm Hg systolic and <85 mm Hg diastolic and only 15% achieved the ADA/NKF goals of <130 mm Hg systolic and <80 mm Hg diastolic. Although goal was achievable in most uncomplicated hypertension, hypertension in diabetes was more difficult to control, despite being more likely to receive enhanced benefit from effective management. Goal-oriented strategy, especially in diabetic subjects, should be aggressively sought rather than relaxing goals to promote achievement.
Steady-State and Dynamic Responses of Renal Sympathetic Nerve Activity to Air-Jet Stress in Sinoaortic Denervated Rats
Authors: Barrès Christian , Cheng Yong , Julien Claude
Published: January 2004

This study examined the role of arterial baroreceptors in mediating the relationship between changes in the mean level and the amplitude of slow oscillations of renal sympathetic nerve activity (RSNA) during environmental stress. In 7 sham-operated (control) and 7 chronically (2 weeks before study) sinoaortic baroreceptor denervated (SAD) conscious rats, arterial pressure (AP) and RSNA were simultaneously recorded during two 15-minute periods, before and during the application of a mild environmental stressor (jet of air). Air-jet stress induced a similar degree of sympathoexcitation in both groups of rats. During stress in control rats, AP and RSNA spectral power in the mid-frequency (MF) range (0.27 to 0.74 Hz) increased, mainly as a consequence of an amplification of strongly coherent oscillations of ≈0.4 Hz frequency. In SAD rats, MF fluctuations of AP and RSNA were reduced but not abolished before stress, tended to increase during stress, and were linearly related under both experimental conditions. However, in the MF range, there was no well-defined oscillation at any specific frequency. At the peak coherence frequency (≈0.4 Hz), the gain of the transfer function from RSNA to AP did not change during stress in control rats and was similar to that measured in SAD rats, indicating that it mainly reflected the properties of the feedforward effect of RSNA on AP (ie, vascular reactivity). In summary, the parallelism between stress-induced changes in the mean level of RSNA and the amplitude of slow RSNA oscillations requires the functional integrity of the baroreceptor reflex, which is consistent with the hypothesis that slow AP and RSNA rhythms are resonant oscillations within the baroreceptor reflex loop.
Nitric Oxide Mediates Benefits of Angiotensin II Type 2 Receptor Overexpression During Post-Infarct Remodeling
Authors: Bove Christina M. , Yang Zequan , Gilson Wesley D. , Epstein Frederick H. , French Brent A. , Berr Stuart S. , Bishop Sanford P. , Matsubara Hiroaki , Carey Robert M. , Kramer Christopher M.
Published: January 2004

We hypothesized that nitric oxide (NO) mediates the benefits of cardiac angiotensin II type 2 (AT
2
-R) overexpression during postmyocardial infarction (post-MI) remodeling. Eleven wild-type (WT) C57BL/6 mice and 28 transgenic (TG) mice with AT
2
-R overexpression were studied by cardiac magnetic resonance imaging (CMR) at baseline and days 1 and 28 post-MI induced by left anterior descending artery occlusion and reperfusion. Sixteen TG mice were treated from day 1 through 28 post-MI with the NO synthase inhibitor
N
G
-nitro-
l
-arginine methyl ester in drinking water at 1 mg/mL (TG-Rx). Left ventricular mass index (LVMI), end-diastolic volume index (EDVI) and end-systolic volume index (ESVI), wall thickness, percent thickening, and ejection fraction (EF) were measured. Infarct size on day 1 was assessed by post-contrast CMR. Interstitial collagen was quantified in noninfarcted regions. At baseline, heart rate (HR), blood pressure (BP), LVMI, EDVI, and ESVI were similar between groups, as were infarct size and weekly post-MI HR and systolic BP. By day 28 post-MI, EDVI and ESVI were similar in WT and TG-Rx, but significantly lower in TG (ESVI: 1.41±0.18 μL/g versus 2.53±0.14 μL/g in WT; 2.17±0.14 μL/g in TG-Rx;
P
<0.008 for both). At day 28, EF was higher in TG (46.3%±2.9%) compared with WT and TG-Rx (32.7±2.3% and 33.7±2.3, respectively;
P
<0.003 for both). Wall thickening at day 28 post-MI was greater in the base and mid-LV in TG than WT and TG-Rx. Noninfarcted region interstitial collagen was similar between groups. Thus, the NO pathway may mediate much of the benefits of cardiac AT
2
-R overexpression during post-MI remodeling.
Low Birth Weight Predicts Higher Blood Pressure But Not Dermal Capillary Density in Two Populations
Authors: Irving R. John , Shore Angela C. , Belton Neville R. , Elton Robert A. , Webb David J. , Walker Brian R.
Published: January 2004

The association between low birth weight and high blood pressure is well established, but underlying mechanisms remain undefined. Vascular rarefaction, which may elevate peripheral vascular resistance, has been observed in capillaries of young men at risk for hypertension and men who had low birth weight. We looked for evidence that capillary rarefaction explains the association of low birth weight with high blood pressure in two cohorts. Participants in study 1 included 107 healthy boys aged 6 to 16 years recruited at random from a single school. Study 2 included 61 members of a cohort recruited at birth and studied at age 24 years. Measurements included indices of current size, blood pressure by automated sphygmomanometer, and dermal capillary density by video capillaroscopy of dorsal index finger skin after 10 minutes of venous occlusion. Lower birth weight predicted higher systolic blood pressure in both studies: in study 1, 3.57 mm Hg/kg birth weight (after adjustment for current height, 95% confidence interval 0.38 to 6.75,
P
<0.05); in study 2, 122±12 mm Hg in low birth weight (<2 kg) versus 115±9 in controls (
P
<0.05). Dermal capillary density was not associated in either group with birth weight or systolic blood pressure. We have found no evidence in these 2 cohorts that reduced capillary density explains the associations between lower birth weight and higher blood pressure.
Cyclooxygenases, the Kidney, and Hypertension
Authors: Cheng Hui-Fang , Harris Raymond C.
Published: January 2004

Selective cyclooxygenase (COX)-2 inhibitors that are in widespread clinical use were developed to avoid side effects of conventional NSAIDs, including gastrointestinal and renal toxicity. However, COX-2 is constitutively expressed in the kidney and is highly regulated in response to alterations in intravascular volume. COX-2 metabolites have been implicated in maintenance of renal blood flow, mediation of renin release, and regulation of sodium excretion. COX-2 inhibition may transiently decrease urine sodium excretion in some subjects and induce mild to moderate elevation of blood pressure. Furthermore, in conditions of relative intravascular volume depletion and/or renal hypoperfusion, interference with COX-2 activity can have deleterious effects on maintenance of renal blood flow and glomerular filtration rate. In addition to physiological regulation of COX-2 expression in the kidney, increased renal cortical COX-2 expression is seen in experimental models associated with altered renal hemodynamics and progressive renal injury (decreased renal mass, poorly controlled diabetes), and long-term treatment with selective COX-2 inhibitors ameliorates functional and structural renal damage in these conditions.
B-Type Natriuretic Peptide Exerts Broad Functional Opposition to Transforming Growth Factor-β in Primary Human Cardiac Fibroblasts
Authors: Kapoun Ann M. , Liang Faquan , O’Young Gilbert , Damm Deborah L. , Quon Diana , White R. Tyler , Munson Kimberly , Lam Andrew , Schreiner George F. , Protter Andrew A.
Published: January 2004

The natriuretic peptides, including human B-type natriuretic peptide (BNP), have been implicated in the regulation of cardiac remodeling. Because transforming growth factor-β (TGF-β) is associated with profibrotic processes in heart failure, we tested whether BNP could inhibit TGF-β–induced effects on primary human cardiac fibroblasts. BNP inhibited TGF-β–induced cell proliferation as well as the production of collagen 1 and fibronectin proteins as measured by Western blot analysis. cDNA microarray analysis was performed on RNA from cardiac fibroblasts incubated in the presence or absence of TGF-β and BNP for 24 and 48 hours. TGF-β, but not BNP, treatment resulted in a significant change in the RNA profile. BNP treatment resulted in a remarkable reduction in TGF-β effects; 88% and 85% of all TGF-β–regulated mRNAs were affected at 24 and 48 hours, respectively. BNP opposed TGF-β–regulated genes related to fibrosis (
collagen 1
,
fibronectin
,
CTGF
,
PAI-1
, and
TIMP3
), myofibroblast conversion (α-smooth muscle actin 2 and nonmuscle myosin heavy chain), proliferation (
PDGFA
,
IGF1
,
FGF18
, and
IGFBP10
), and inflammation (
COX2
,
IL6
,
TNF
α-
induced protein 6
, and
TNF superfamily
,
member 4
). Lastly, BNP stimulated the extracellular signal-related kinase pathway via cyclic guanosine monophosphate–dependent protein kinase signaling, and two mitogen-activated protein kinase kinase inhibitors, U0126 and PD98059, reversed BNP inhibition of TGF-β–induced collagen-1 expression. These findings demonstrate that BNP has a direct effect on cardiac fibroblasts to inhibit fibrotic responses via extracellular signal-related kinase signaling, suggesting that BNP functions as an antifibrotic factor in the heart to prevent cardiac remodeling in pathological conditions.
Cardiac Stem Cell and Myocyte Aging, Heart Failure, and Insulin-Like Growth Factor-1 Overexpression
Authors: Torella Daniele , Rota Marcello , Nurzynska Daria , Musso Ezio , Monsen Alyssa , Shiraishi Isao , Zias Elias , Walsh Kenneth , Rosenzweig Anthony , Sussman Mark A. , Urbanek Konrad , Nadal-Ginard Bernardo , Kajstura Jan , Anversa Piero , Leri Annarosa
Published: January 2004

To determine whether cellular aging leads to a cardiomyopathy and heart failure, markers of cellular senescence, cell death, telomerase activity, telomere integrity, and cell regeneration were measured in myocytes of aging wild-type mice (WT). These parameters were similarly studied in insulin-like growth factor-1 (IGF-1) transgenic mice (TG) because IGF-1 promotes cell growth and survival and may delay cellular aging. Importantly, the consequences of aging on cardiac stem cell (CSC) growth and senescence were evaluated. Gene products implicated in growth arrest and senescence, such as p27
Kip1
, p53, p16
INK4a
, and p19
ARF
, were detected in myocytes of young WT mice, and their expression increased with age. IGF-1 attenuated the levels of these proteins at all ages. Telomerase activity decreased in aging WT myocytes but increased in TG, paralleling the changes in Akt phosphorylation. Reduction in nuclear phospho-Akt and telomerase resulted in telomere shortening and uncapping in WT myocytes. Senescence and death of CSCs increased with age in WT impairing the growth and turnover of cells in the heart. DNA damage and myocyte death exceeded cell formation in old WT, leading to a decreased number of myocytes and heart failure. This did not occur in TG in which CSC-mediated myocyte regeneration compensated for the extent of cell death preventing ventricular dysfunction. IGF-1 enhanced nuclear phospho-Akt and telomerase delaying cellular aging and death. The differential response of TG mice to chronological age may result from preservation of functional CSCs undergoing myocyte commitment. In conclusion, senescence of CSCs and myocytes conditions the development of an aging myopathy.
Framingham Stroke Risk Profile and Lowered Cognitive Performance
Authors: Elias Merrill F. , Sullivan Lisa M. , D’Agostino Ralph B. , Elias Penelope K. , Beiser Alexa , Au Rhoda , Seshadri Sudha , DeCarli Charles , Wolf Philip A.
Published: January 2004

Background and Purpose—

The primary objective of this work was to describe the relationships between 10-year risk for stroke and multiple measures of cognitive performance for a large community-based sample of individuals who were free of clinical stroke and dementia at the time of risk assessment.

Methods—

Participants were 1011 men and 1164 women from the Framingham Offspring Study. The Framingham Stroke Risk Profile was used to assess 10-year risk of stroke. Using a cross-sectional design, we assessed 10-year risk of stroke, the predictor variable, and cognitive performance, the outcome variable, at examination 7 of the Framingham Offspring Study. Multivariable linear regression models were used to relate 10-year risk of stroke to cognitive tests measuring multiple domains of cognitive functioning.

Results—

With statistical adjustment for age, education, sex, and other correlates of both stroke and cognitive ability, an inverse association between increments in 10-year risk of stroke and cognitive performance level was observed for tests indexing visual-spatial memory, attention, organization, scanning, and abstract reasoning.

Conclusions—

In stroke- and dementia-free individuals, higher 10-year risk for stroke is associated with performance decrements in multiple cognitive domains.
Educational Level and Stroke Mortality
Authors: Avendaño Mauricio , Kunst Anton E. , Huisman Martijn , van Lenthe Frank , Bopp Matthias , Borrell Carme , Valkonen Tapani , Regidor Enrique , Costa Giuseppe , Donkin Angela , Borgan Jens-Kristian , Deboosere Patrick , Gadeyne Sylvie , Spadea Teresa , Andersen Otto , Mackenbach Johan P.
Published: January 2004

Background and Purpose—

Variations between countries in occupational differences in stroke mortality were observed among men during the 1980s. This study estimates the magnitude of differences in stroke mortality by educational level among men and women aged ≥30 years in 10 European populations during the 1990s.

Methods—

Longitudinal data from mortality registries were obtained for 10 European populations, namely Finland, Norway, Denmark, England/Wales, Belgium, Switzerland, Austria, Turin (Italy), Barcelona (Spain), and Madrid (Spain). Rate ratios (RRs) were calculated to assess the association between educational level and stroke mortality. The life table method was used to estimate the impact of stroke mortality on educational differences in life expectancy.

Results—

Differences in stroke mortality according to educational level were of a similar magnitude in most populations. However, larger educational differences were observed in Austria. Overall, educational differences in stroke mortality were of similar size among men (RR, 1.27; 95% CI, 1.24 to 1.30) and women (RR, 1.29; 95% CI, 1.27 to 1.32). Educational differences in stroke mortality persisted at all ages in all populations, although they generally decreased with age. Eliminating these differences would on average reduce educational differences in life expectancy by 7% among men and 14% among women.

Conclusions—

Educational differences in stroke mortality were observed across Europe during the 1990s. Risk factors such as hypertension and smoking may explain part of these differences in several countries. Other factors, such as socioeconomic differences in healthcare utilization and childhood socioeconomic conditions, may have contributed to educational differences in stroke mortality across Europe.
Human Serum Albumin and its N-Terminal Tetrapeptide (DAHK) Block Oxidant-Induced Neuronal Death
Authors: Gum Elizabeth T. , Swanson Raymond A. , Alano Conrad , Liu Jialing , Hong Shwuhuey , Weinstein Philip R. , Panter S. Scott
Published: January 2004

Background and Purpose—

Studies using animal models of stroke have shown that human serum albumin (HSA) significantly ameliorates cerebral ischemic injury after both transient and permanent ischemia, even when administered after the onset of ischemia or reperfusion. The mechanism of this effect remains uncertain, and prior studies suggest both indirect hemodynamic and direct cytoprotective effects. HSA is a potent antioxidant, in part because of its strong copper-binding capacity. Here we examined the effect of HSA on oxidant-induced neuronal death in a cortical cell culture system.

Methods—

Murine cortical cultures were exposed to oxidative stress generated by hydrogen peroxide and by a mixture of copper plus ascorbic acid. We examined the ability of HSA and a tetrapeptide occupying its N-terminus (DAHK) to prevent neuronal death after these challenges.

Results—

H
2
O
2
and CuCl
2
/ascorbic acid were used at concentrations that, in the absence of HSA, killed >90% of the neurons. HSA provided complete protection at a concentration of 37.5 μmol/L and 50% protection at 3.75 μmol/L. The copper-binding tetrapeptide DAHK had nearly identical potency and efficacy. HSA and DAHK were also equally effective in preventing neuronal death induced by CuCl
2
/ascorbic acid.

Conclusions—

HSA has potent antioxidant properties, probably due to binding of copper and other transition metals. HSA extravasation into ischemic brain may provide neuroprotection by limiting metal-catalyzed oxidant stress. The tetrapeptide DAHK may be an effective, small-molecular-weight alternative to HSA as a therapeutic agent for stroke.
Agreement Between Patient and Proxy Assessments of Health-Related Quality of Life After Stroke Using the EQ-5D and Health Utilities Index
Authors: Pickard A. Simon , Johnson Jeffrey A. , Feeny David H. , Shuaib Ashfaq , Carriere K.C. , Nasser Abdul M.
Published: January 2004

Background and Purpose—

Proxy informants can provide information on patients who are limited in ability to self-assess health-related quality of life (HRQL) after stroke. One alternative is to exclude assessments of such patients and attenuate generalizability. The purpose of this study was to examine patient-proxy agreement on the domains and summary scores of the EQ-5D and Health Utilities Index Mark 3 (HUI3) after stroke.

Methods—

An observational longitudinal cohort of 124 patients hospitalized after ischemic stroke and their family caregivers completed the HRQL measures at baseline and were followed up for 6 months. Patient and proxy agreement was assessed by use of weighted κ or the intraclass correlation coefficient (ICC).

Results—

At baseline, the more observable domains of HRQL demonstrated greater agreement than the more subjective components. Cross-sectional point estimates of agreement were generally acceptable (ICC >0.70) for the EQ-5D Index and HUI3 summary scores when assessed ≥1 month after baseline. Agreement between change scores was generally poor to fair (ICC <0.60), but systematic bias was not observed for the indirect preference-based summary scores between baseline and 6 months.

Conclusions—

Results suggest that proxy assessments obtained 6 months after stroke are more reliable than those obtained within 2 to 3 weeks after stroke. Although proxy-assessed change scores for indirect preference-based summary scores of the EQ-5D and HUI3 provided suboptimal agreement with patient assessment, limited systematic bias may support their consideration as alternatives to missing data or statistical imputation. Further research into the validity and reliability of proxy assessments is suggested.
Mild Neurological Symptoms Despite Middle Cerebral Artery Occlusion
Authors: Coutts Shelagh B. , Barber Philip A. , Demchuk Andrew M. , Hill Michael D. , Pexman J.H. Warwick , Hudon Mark E. , Buchan Alastair M.
Published: January 2004

Background and Purpose—

Only a small percentage of stroke patients are treated with thrombolytic therapy. We sought to determine whether vessel occlusion in mild strokes represented a new target population for interventional therapy.

Methods—

We imaged 106 acute stroke patients with MRI. Patients were identified with evidence of middle cerebral artery (MCA) occlusion and mild or no stroke signs (National Institutes of Health Stroke Scale [NIHSS] ≤3). They were compared with patients with signs of stroke, NIHSS >3, and MCA occlusion.

Results—

We identified 5 patients with absent flow on MRA in the MCA and mild or no stroke signs (NIHSS ≤3). All 5 were functionally independent at 3 months.

Conclusions—

Caution should be exercised in considering thrombolytic therapy in these patients. Quantification of perfusion imaging is required to identify “at risk” mild stroke populations.
Coactivation of GABA
A
and GABA
B
Receptor Results in Neuroprotection During In Vitro Ischemia
Authors: Costa Cinzia , Leone Giorgia , Saulle Emilia , Pisani Francesco , Bernardi Giorgio , Calabresi Paolo
Published: January 2004

Background and Purpose—

The possible neuroprotective effect of endogenous γ-aminobutyric acid (GABA) on the irreversible electrophysiological changes induced by in vitro ischemia on striatal neurons was investigated. In particular, the aim of the study was the characterization of the neuroprotective action of 2 antiepileptic drugs increasing GABAergic transmission such as tiagabine, a GABA transporter inhibitor, and vigabatrin, an irreversible inhibitor of GABA transaminase.

Methods—

Extracellular field potential recordings were obtained from rat corticostriatal slice preparations. In vitro ischemia was delivered by switching to an artificial cerebrospinal fluid solution in which glucose was omitted and oxygen was replaced with N
2
.

Results—

An irreversible loss of the field potentials recorded from striatal neurons was observed after 10 minutes of ischemia in control solution. Conversely, tiagabine and vigabatrin partially prevented the ischemia-induced field potential loss. Surprisingly, both GABA
A
and GABA
B
receptor antagonists blocked these effects. Accordingly, neuroprotection could be obtained only when GABA
A
and GABA
B
receptor agonists were coapplied, but not when a single agonist was given in isolation.

Conclusions—

Antiepileptic drugs targeting GABAergic transmission can exert neuroprotective effects against ischemia by increasing endogenous GABA levels and via the activation of both GABA
A
and GABA
B
receptors.
Association Between High Serum Ferritin Levels and Carotid Atherosclerosis in the Study of Health in Pomerania (SHIP)
Authors: Wolff Birger , Völzke Henry , Lüdemann Jan , Robinson Daniel , Vogelgesang Dirk , Staudt Alexander , Kessler Christof , Dahm Johannes B. , John Ulrich , Felix Stephan B.
Published: January 2004

Background and Purpose—

Several studies have provided evidence for a relationship between body iron load and cardiovascular disease. We analyzed the association of serum ferritin levels with carotid atherosclerosis.

Methods—

We assessed intima-media thickness and plaque prevalence in the carotid arteries by high-resolution ultrasound among 2443 participants (1200 women; age, 45 to 79 years) in the Study of Health in Pomerania (SHIP), a population-based study in northeast Germany.

Results—

In multivariate analysis, serum ferritin levels were not independently associated with carotid intima-media thickness among women or men. In contrast, the relationship between serum ferritin levels and carotid plaque prevalence was significant among men (odds ratio per 1-SD increase of serum ferritin levels, 1.33; 95% confidence interval, 1.08 to 1.44) yet not among women (odds ratio, 1.29; 95% confidence interval, 0.98 to 1.75). However, both men and women showed a dose-response relation between serum ferritin levels and carotid atherosclerosis in which higher serum ferritin levels were associated with greater odds ratios for carotid plaque prevalence. Additionally, there was an interaction of serum ferritin levels with low-density lipoprotein (LDL) cholesterol (
P
=0.039) among men in which the association of serum ferritin levels with carotid plaque prevalence became stronger with increasing LDL cholesterol levels.

Conclusions—

Our study identified a relationship between serum ferritin levels and carotid atherosclerosis that was potentiated by LDL cholesterol. This relationship adds support to the hypothesis of a link between iron and cardiovascular disease.
Effect of Presputtering on Plasma Ion Nitriding of Aluminium Substrates
Authors: Figueroa U. , Salas O. , Oseguera J. , Rodríguez S. , Ruiz B.
Published: January 2004

The relative effect of the presputtering treatment on the formation of AlN on Al substrates by ion plasma nitriding is investigated. In particular, presputtering time and temperature are considered. Samples of a commercial 7022-T6 Al alloy were nitrided in a two step process consisting of a presputtering stage in which time and temperature were varied and a nitriding stage carried out in the same conditions for all samples. The treated samples were characterised by optical and scanning electron microscopy and energy dispersive X-ray microanalysis, by glancing angle X-ray diffraction and by X-ray photoelectron spectroscopy. An optimal sputtering time was found for the production of thick, uniform AlN layers on the substrates. A higher presputtering temperature resulted in a shorter optimal presputtering time.
Abrasive Wear Behaviour of Cobalt and Nickel Electrodeposited Surfaces with Cr2O3 Dispersions
Authors: Chandramohan R. , Kumar K. , Kalyanaraman D.
Published: January 2004

Electrochemically deposited composite coatings are of interest nowadays owing to the flexibility of the deposition process and to the increasing demand for highly wear resistant composite coatings. In electrochemically deposited coatings, a second phase such as fine tough particles is incorporated in the coating matrix to improve the surface mechanical properties. In the present work, the surface mechanical behaviour of cobalt and nickel coatings with dispersion of chromium oxide in the matrix is reported. The effect of heat treatment of these coatings on the surface mechanical properties is also studied. The surface microhardness and wear loss due to rubbing abrasion are studied before and after heat treatment in the range of 100 - 600 ° C and are reported for both systems. The composite containing 12 vol.-% chromium oxide (Cr2O3) in a cobalt matrix and heat treated at 500 - 600 ° C was found to exhibit high abrasive resistance. This is attributed to the formation of a glass-like layer found in the cobalt matrix. The coatings are found to be highly adherent and uniform and suitable for high temperature applications.
Origin and distribution of clay minerals in calcareous arid and semi-arid soils of Fars Province, southern Iran
Authors: Khormali F. , Abtahi A.
Published: January 2004

The clay mineralogy of soils and of the main calcareous sedimentary parent rocks of southern Iran were investigated to determine their origin and factors controlling their distribution pattern in soils. The results revealed that the soil-available moisture plays the major role in the distribution pattern of palygorskite and smectite clay minerals in the arid and semi-arid areas studied. There is an inverse correlation between palygorskite and smectite with regard to the soil-available moisture as expressed by P/ETº (ratio of mean annual precipitation to mean annual reference crop evapotranspiration). At P/ETº values >0.4 palygorskite transforms to smectite. Smectite is thought to be mainly of ‘transformed’ origin. It is detected in trace amounts in soils of more arid areas and increases in soils having greater available moisture. The general decrease in illite content with depth is related mainly to its transformation to smectite under favourable moisture conditions of the deeper horizons. Palygorskite is considered to be inherited in plateau soils of the arid regions whereas in saline and alkaline soils and soils with high gypsum, it is mainly of authigenic origin. The P/ETº and gypsum content show a significant correlation with the palygorskite content. The occurrence of kaolinite in some soils is due to its inheritance from the surrounding kaolinite-bearing Cretaceous rocks. Illite and chlorite abundance in soils is also largely related to their presence in parent rocks. The rare occurrence of vermiculite in the studied calcareous soils is mainly related to its lower stability under high pH, low Al activity and the presence of large amounts of Si and Mg in soils.
Structural and chemical heterogeneity of layer silicates and clay minerals
Authors: Drits V. A.
Published: January 2004

Different forms of structural and chemical heterogeneity are considered including mixed-layer minerals, disordered layer structures containing rotational and translational stacking faults, interstratification oftrans-vacant (tv) andcis-vacant (cv) layers in true micas, illites and illitesmectite (I-S), short-range order in isomorphous cation distribution etc.

Because determination of various structural and chemical imperfections requires elaboration of new diffraction and spectroscopic methodologies, special attention is paid to recent achievements in the development of new methodological approaches such as a multispecimen simulation of experimental X-ray diffraction (XRD) patterns from mixed-layer minerals, with account taken of layer-thickness fluctuations of the second type and possible difference between structures of outer and core layers; experimental determination of thickness distribution of illite crystals by HRTEMand the modified Bertaut-Warren-Averbach technique; XRD and thermal methods for determination ofcvandtvlayers in true micas, illites and I-S; generalization of Méring's rules to account for the behaviour of non-basal reflections for any defective structure in which two translations are irregularly interstratified; variousab initiocalculations devoted to modelling infrared OH vibrations, octahedral cation distribution in dioctahedral 2:1 layer silicates, etc. It is shown that these recentlydeveloped methodologies have revealed new diversity in the structural and chemical heterogeneity of phyllosilicates and clay minerals, provided new insight into the structural mechanisms of their transformation in different geological environments, and discovered new natural processes.
Transmission electron microscopy study of very low-grade metamorphic evolution in Neoproterozoic pelites of the Puncoviscana formation (Cordillera Oriental, NW Argentina)
Authors: Do Campo M. , Nieto F.
Published: January 2004

The Puncoviscana Formation, largely cropping out in NW Argentina, is mainly composed of a pelite-greywacke turbidite sequence affected by incipient regional metamorphism and polyphase deformation. Metapelites, composed mainly of quartz, albite, dioctahedral mica and chlorite, were sampled in the Lules-Puncoviscana and Choromoro belts. Lattice-fringe images, selected area electron diffraction and analytical electron microscopy analyses, coupled with previous data from white mica crystallinity index, indicate a state of reaction progress for Puncoviscana slates consistent with medium anchizone- to epizone-grade metamorphism. The 2Mpolytype prevails in dioctahedral micas, coexisting in a few cases with the 1Mdpolytype as a consequence of lack of equilibrium. The 2Mpolytype coexists with 3Tin two slates and long-range four-layer and ten-layer stacking sequences were identified in another sample. Samples with 3Tand long-range stacking sequences presentbvalues characteristic of intermediate–high pressure metamorphism and ordered chlorites (1L, 2L, 3Land 7L) prevail.

Based on the Si contents of dioctahedral micas and considering peak temperatures of ∼350 –400ºC, pressures from 5 kbar and 5 –7 kbar were derived for metapelites from the Lules- Puncoviscana and Choromoro belts, respectively. These values agree with facies series derived from thebvalues. Micas with a wide range of phengitic substitution, as evidenced by Fe + Mg and Si contents, coexist. These variations could not arise from the disturbing effect of detrital white K-mica because TEM evidence indicates that they are absent or represent <10% of the mica population. Thus, compositional variations suggest that dioctahedral micas of individual slates crystallized at different pressure conditions in response to theP-Tpath of the metamorphism. Moreover, in several biotite-free slates the illite crystallinity (IC) values lead to an underestimation of the metamorphic grade attained in these rocks.

The coexistence of IC corresponding to anchizone and the occurrence of biotite in some slates and felsic metavolcanic rocks intercalated in the Puncoviscana metasediments are interpreted to be the result of a metamorphic path including a relatively high-pressure/ low-temperature (HP/LT) event, followed by a lower-pressure overprint possibly at higher temperatures than the HP/LTevent. Small micas formed during the high-pressure stage would prevail in the <2 mm fraction, producing anchizone IC.
Visible absorption spectroscopy study of the adsorption of Congo Red by montmorillonite
Authors: Yermiyahu Z. , Lapides I . , Yariv S.
Published: January 2004

The adsorption of the anionic dye Congo Red (CR) by Na-, Cs-, Mg-, Cu-, Al- and Fe-montmorillonite was investigated by electronic spectroscopy. Spectra of the aqueous suspensions of different clay concentrations and different loadings were recorded. The spectra were curve fitted and were compared to spectra of aqueous solutions of CR at different pH values. Four bands representing anionic varieties and two representing protonated varieties of CR were identified in spectra of CR-treated Na-, Cs-, Mg-, Cu- and Al-montmorillonite. Spectra of CR-treated Femontmorillonite were slightly different, showing three bands representing anionic varieties and four representing protonated CR. The ratio between areas of bands, which represent the protonated varieties, and those representing the anionic varieties were determined showing correlation with the acidity of the metallic cation. The clay in the aqueous suspensions became coloured after the adsorption of CR. The following stainings were obtained, Na- and Mg-clay, red, Cs-clay, violet-red, Cu-clay, reddish-violet, Al-clay, dark violet and Fe-clay, dark blue. It appears that CR can serve as an indicator of the surface acidity of montmorillonite. The effects of aging on the sorption of the dye and on the surface-acidity of the CR-clay complex were investigated.
Alteration of volcanic rocks and genesis of kaolin deposits in the Şile Region, northern İstanbul, Turkey. Part II: differential mobility of elements
Authors: Ece O. I. , Nakagawa Z.-E
Published: January 2004

In the area of S° ile, NW Turkey, Upper Cretaceous calc-alkaline volcanic rocks with compositions ranging from andesite to rhyolite have been recognized. The most widespread rocks of the suite are andesites, which can be grouped into altered and fresh. The oldest altered andesites are the parent rocks for the kaolin deposits of the study area. The Upper Cretaceous volcanic suite consists of spilite, basalt, andesite, trachyandesite, trachyandesitic and hyaloandesitic dacite, rhyolite lavas, tuffs and agglomerates. The highly altered andesites are composed of plagioclase, pyroxene, hornblende, biotite, augite and very fine opaque minerals. During the Turonian, an E –W trending extensional magmatic arc was developed in the Istanbul Tectonic Zone of the oceanic Western Black Sea basin and intermediate volcanic rocks were emplaced, mostly calc-alkaline andesites, suggesting multi-stage magmatism. The significant features of the andesites are: (1) enrichment of LILE (Rb, Ba, K) over HFSE (Zr, Nb, Hf, Ti, Th, U, Y) and LREE (La –Sm), resulting in high Ba/Nb, Th/Nb, Ba/La, K/Ti and Th/La ratios; (2) depletion of LREE over HFSE, MREE and HREE, generating high La/Nb, Ce/Ti, La/Sm and La/Y values; and (3) depletion of Nb, Sr and Ti; all of which are typical of island arc magmatism, with possible back arc signature. The Th-Hf-Ta diagram for tectonomagmatic classification shows that the S° ile calc-alkaline rocks are similar to volcanic rocks from the Mariana Arc, the Aeolian Arc of Salina, Italy, the Skaros island in the Aegean Sea and Sardinia's ignimbrites. Moreover, relatively low La/Th and Ce/Pb ratios suggest that the source region of volcanism was enriched in LILE with respect to REE, indicating crustal contamination during melting.

Highly weathered andesitic rocks, rich in smectite, were transported gradually and deposited in a lacustrine basin, a coal-forming dysaerobic environment, in which they were subject to post-depositional alteration, or in situkaolinization, to form a kaolin deposit in the presence of humic and fulvic acids. The mobility of major and trace elements and REEs during the progressive kaolinization of andesitic materials has been investigated to reveal the geochemical characteristics of Upper Cretaceous volcanic parent rocks and to explain mineralogical processes in a kaolin deposit as a daughter rock ‘end-product’ . Alteration is characterized by the loss of Si, Fe, Ca, Na and K, and by the gain of Al, Ti, Zr and LOI. Moreover, Ho, Er and Yb are immobile, and Hf, Zr and Nb are mobile. Th and U are slightly enriched in clay horizons with respect to the andesitic rocks. In addition, Cr, Ga, Nb and Ta enrichments indicate variable sources of terrigenous sediments and differential mobilities of elements in lake waters rich in organic acids. The anatase concentration increases in the <2 mm size fractions as subspherical particles and these precipitate at acidic conditions (pH ≈ 5) during early diagenesis.
29Si and27Al MAS NMR study of the thermal transformations of kaolinite from North China
Authors: He H. P. , Guo J . G. , Zhu J . X. , Hu C.
Published: January 2004

The thermal transformations of kaolinite have been studied using27Al and29Si magic angle spinning nuclear magnetic resonance (MAS NMR), X-ray diffraction (XRD), differential thermal analysis (DTA) and thermogravimetric analysis (TG). The experimental results show that this sample is a pure kaolinite which contains ∼3% carbonaceous material as impurity.27Al and29Si MAS NMR spectra show that the microstructural evolution of the thermal transformation of kaolinite at 450 –1050ºC is similar to that of the kaolinite– mullite reaction series previously published by many authors.29Si MAS NMR spectra of mullite at 1190 and 1250ºC display two resonances at ∼ – 87 and –92 ppm, corresponding to sillimanite-type geometry around Si and the typical Si environment of mullite, respectively. At 1350ºC, the splitting of (hk0) and (kh0) of mullite occurs, indicating that the primary mullite transforms into orthorhombic mullite. Simultaneously, the resonance at ∼ – 92 ppm splits into two signals at ∼ –90 and –94 ppm.27Al MAS NMR spectra of the mullite consist of three signals centred at ∼ –4, 45 and 60 ppm, corresponding to octahedral, distorted tetrahedral and tetrahedral Al sites, respectively.
Cytosolic phospholipase A2 type IVA is present in human red cells
Authors: Macdonald Donald J. , Boyle Rose M. , Glen Alastair C. A. , Horrobin David F.
Published: January 2004

Phospholipase A2 type IVA (IVAPLA2) is a cytosolic enzyme that on activation selectively releases arachidonic acid (AA) from cell membrane phospholipids. Both AA and lysophospholipid, products of the enzymic reaction, can function as signal transducers in cellular interactions. The enzyme is present in most cells, including polymorphs, eosinophils, and platelets. This study used affinity purification to extract IVAPLA2 from red cell lysate prepared from leukocyte- and platelet-depleted human blood to overcome the masking effect of hemoglobin on Western blot detection. We show that IVAPLA2 is present in red cells as a 90-kDa protein. (Blood. 2004;103:3562-3564)
WASp deficiency in mice results in failure to form osteoclast sealing zones and defects in bone resorption
Authors: Calle Yolanda , Jones Gareth E. , Jagger Chris , Fuller Karen , Blundell Mike P. , Chow Jade , Chambers Tim , Thrasher Adrian J.
Published: January 2004

No defects related to deficiency of the Wiskott-Aldrich Syndrome protein (WASp) have been described in osteoclasts. Here we show that there are significant morphologic and functional abnormalities. WASp-null cells spread over a much larger surface area and are highly polykaryotic. In their migratory phase, normal cells assemble clusters of podosomes behind their leading edges, whereas during the bone resorptive phase multiple podosomes are densely aggregated in well-defined actin rings forming the sealing zone. In comparison, WASp-null osteoclasts in either phase are markedly depleted of podosomes. On bone surfaces, this results in a failure to form actin rings at sealing zones. Complementation of WASp-null osteoclasts with an enhanced green fluorescent protein (eGFP)-WASp fusion protein restores normal cytoarchitecture. These structural disturbances translate into abnormal patterns of bone resorption both in vitro on bone slices and in vivo. Although physiologic steady-state levels of bone resorption are maintained, a major impairment is observed when WASp-null animals are exposed to a resorptive challenge. Our results provide clear evidence that WASp is a critical component of podosomes in osteoclasts and indicate a nonredundant role for WASp in the dynamic organization of these actin structures during bone resorption. (Blood. 2004;103:3552-3561)