bluuebunny/crossref_metadata_2025 huggingface dataset:
Erythrocyte Membrane Phospholipid Composition as a Biomarker of Dietary Fat
Authors: Fuhrman Barbara J. , Barba Maddalena , Krogh Vittorio , Micheli Andrea , Pala Valeria , Lauria Rossella , Chajes Veronique , Riboli Elio , Sieri Sabina , Berrino Franco , Muti Paola
Published: December 2005

Background/Aims: In a cross-sectional study, we investigated the relationship between erythrocyte membrane phospholipid fatty acid composition and dietary fat; we also investigated roles of menopausal status, age, body mass index (BMI) and waist-to-hip ratio (WHR) in interindividual variation of the biomarker. Methods: Study participants were 204 women, aged 39–65 years, drawn from the ORDET cohort and selected as controls in a study of breast cancer. Membrane composition was assessed using capillary gas chromatography. Dietary fat composition was evaluated using a food frequency questionnaire. Results: In pre- and postmenopausal women, erythrocyte membrane phospholipid levels of linoleic acid, oleic acid, and mono-unsaturated fatty acids were significantly associated with corresponding dietary measures (partial correlation coefficients: 0.23 and 0.39; 0.45 and 0.47; 0.40 and 0.48; respectively, in pre- and postmenopausal women). Among postmenopausal women, membrane poly-unsaturated fatty acids were correlated with the corresponding dietary measure (r = 0.39, p < 0.001). Membrane eicosapentanoic and docosahexanoic acid levels were significantly correlated with intake of fish/shell fish : r = 0.21 and r = 0.43 (premenopausal), and r = 0.41 and r = 0.44 (postmenopausal). Age, BMI and WHR had independent effects on membrane lipid composition. Age was associated with delta-6 desaturase activity in postmenopausal women (r = 0.25, p < 0.05). BMI was negatively associated with delta-9 desaturase activity in both pre- and postmenopausal women (r = –0.29, p = 0.01 and r = –0.22, p < 0.01, respectively). WHR was negatively associated with delta-5 desaturase activity in pre-menopausal women (r = –024, p < 0.05). Conclusions: Erythrocyte membrane levels of some specific fatty acids can be used as biomarkers of these fatty acids as proportions of dietary fat.
Assessment of Cardiovascular Risk Factors among Hungarian University Students in Budapest
Authors: Antal Magda , Nagy Katalin , Regöly-Mérei Andrea , Bíró Lajos , Szabó Csaba , Rabin Borsika
Published: December 2005

Background/aims: The lack of data regarding cardiovascular risk factors among university students in Hungary prompted us to undertake a cross-sectional pilot study in students at Semmelweis University, Budapest. Methods: A total of 264 students (78 males, mean age 21.4 ± 2.6 years, and 186 females, mean age 21.2 ± 2.6 years) participated in the study. Anthropometric measures, blood pressure and serum lipid parameters were investigated. The relationship between body mass index and cardiovascular disease risk factors were analyzed. Results: The occurrence of overweight and abdominal obesity was significantly higher in the male group. The mean serum lipid values were within the acceptable range for both genders; however, in a significantly greater number of male than female students the HDL-cholesterol concentration (<1 mmol/l) was in the low range. High lipoprotein(a) values were seen in 33% of the male and 22.6% of the female students. In both groups of students the body mass index exhibited a positive correlation with waist circumference, total cholesterol, LDL-cholesterol, apolipoprotein B (p < 0.01), and systolic and diastolic blood pressure. In the female students there was an inverse correlation between body mass index and HDL-cholesterol concentrations. Conclusions: The anthropometric and lipid parameters of the student population studied were more favorable than those for an age-matched Hungarian youth population. Nevertheless, the higher occurrence of elevated blood pressure, overweight, abdominal obesity, lower HDL-cholesterol in the male group should be regarded as a warning sign, all the more since their diet was imbalanced and their knowledge in this field was incomplete. The results of our preliminary study point out the importance of teaching nutrition more efficiently, not only during university training but also at an earlier age.
Hemodynamic Effects of Di-Sec-Butyl Phenol, an Anesthetic Substituted Phenol
Authors: Ya Deau Jacques T. , Heerdt Paul M. , The Andrew H.S. , Wang Qingwen
Published: December 2005

Dose- and age-related hemodynamic effects were determined for an anesthetic substituted phenol, 2,6-di-sec-butyl phenol (DSB). DSB, 7.5 mg/kg, induced hypnosis in young rabbits and increased mean blood pressure to 170 ± 14% and heart rate to 150 ± 21% of control values. In elderly rabbits, 7.5 mg/kg DSB induced hypnosis, had no effect on blood pressure, but increased the heart rate to 130 ± 2% of control. After ganglionic blockade with hexamethonium, 7.5 mg/kg DSB caused a decline in mean blood pressure (71 ± 5% of control) without change in heart rate. DSB increased norepinephrine release from SH-SY5Y cells, a human neuroblastoma cell line (5.4 ± 1.7% vs. 3.5 ± 0.3%). DSB produced age-dependent elevation of mean blood pressure in rabbits, probably by causing release of catecholamines from the sympathetic nervous system.
Allergy Practice Worldwide: A Report by the World Allergy Organization Specialty and Training Council
Authors: Warner John O. , Kaliner Michael A. , Crisci Carlos D. , Del Giacco Sergio , Frew Anthony J. , Liu G.H. , Maspero Jorge , Moon Hee-Bom , Nakagawa Takemasa , Potter Paul C. , Rosenwasser Lanny J. , Singh Anand B. , Valovirta Erkka , van Cauwenberge Paul
Published: December 2005

In 2004 the World Allergy Organization’s Specialty and Training Council conducted a survey of World Allergy Organization (WAO) member societies to obtain information about the status of the specialty of allergy worldwide. Responses were received from 33 countries, representing a population of 1.39 billion people, of whom it was estimated that 22% may suffer from some form of allergic disease. Allergy was reported by 23 respondents to be a certified or accredited specialty in their country, and the number of certified allergists per head of population ranged from 1:25 million to 1:16,000. Allergists were ranked as the fifth most likely clinicians to see cases of allergic asthma, third most likely to see allergic rhinitis, and fourth most likely to see eczema or sinusitis. Nine countries only reported that children with allergic diseases would be seen by a pediatrician with appropriate training. The survey results highlight a pressing need for the development of allergy services worldwide.
Cognitive Assessment of the Non-Demented Elderly Community Dwellers in Spain
Authors: Graciani Auxiliadora , Banegas José R. , Guallar-Castillón Pilar , Domínguez-Rojas Vicente , Rodríguez-Artalejo Fernando
Published: December 2005

Objective: The prevalence of cognitive impairment and population normative values for cognitive function were assessed, for the first time, in 2,630 subjects representative of the non-demented community dweller population ≧65 years in Spain, a southern European country with a sizable proportion of illiterate senior citizens. Methods: Data were collected cross-sectionally by interview, using a structured questionnaire. Cognitive function was assessed using the Mini-Examen Cognoscitivo (MEC; Spanish-validated version of the Mini-Mental State Examination). Results: A total of 22.4% of the subjects presented with cognitive impairment (MEC ≤22). The proportion of subjects with cognitive impairment was double in women versus men, rose to 46.2% in subjects aged ≧85 years and to 34.8% in subjects with no formal education, and was higher among those who had limitations in instrumental activities of daily living (p < 0.001). In subjects with no formal education, 25% registered mean MEC scores compatible with probable cognitive impairment. Conclusions: One of every 5 Spanish senior citizens presents with cognitive impairment, a proportion that increased among women, subjects with no formal education and with higher age.
Cognitive Impairment in Patients with Idiopathic Normal Pressure Hydrocephalus
Authors: Ogino Atsushi , Kazui Hiroaki , Miyoshi Noriko , Hashimoto Mamoru , Ohkawa Shingo , Tokunaga Hiromasa , Ikejiri Yoshitaka , Takeda Masatoshi
Published: December 2005

Cognitive impairment in patients with idiopathic normal pressure hydrocephalous (iNPH) has not been clearly documented. We performed standardized neuropsychological assessments of 21 patients with iNPH and of 42 patients with Alzheimer’s disease (AD) matched to the patients with iNPH 2:1 by age, sex, and Mini-Mental State Examination score. Compared with the AD group, the iNPH group scored significantly higher on the orientation subtest of the Alzheimer’s Disease Assessment Scale and on the general memory and delayed recall subtests of the Wechsler Memory Scale-Revised (WMS-R), and significantly lower on the attention/concentration subtest of the WMS-R and on the digit span, arithmetic, block design and digit symbol substitution subtests of the Wechsler Adult Intelligence Scale-Revised. The impairment of frontal lobe functions is disproportionately severe and memory impairment is disproportionately mild in patients with iNPH compared with AD. Recognition of these features contributes to an early diagnosis, which can lead to a better prognosis.
Age Is an Important Determinant of the Growth Hormone Response to Sprint Exercise in Non-Obese Young Men
Authors: Stokes Keith , Nevill Mary , Hall George
Published: December 2005

Background:The factors that regulate the growth hormone (GH) response to physiological stimuli, such as exercise, are not fully understood. The aim of the present study is to determine whether age, body composition, measures of sprint performance or the metabolic response to a sprint are predictors of the GH response to sprint exercise in non-obese young men. Methods:Twenty-seven healthy, non-obese males aged 18–32 years performed an all-out 30-second sprint on a cycle ergometer. Univariate linear regression analysis was employed to evaluate age-, BMI-, performance- and metabolic-dependent changes from pre-exercise to peak GH and integrated GH for 60 min after the sprint. Results:GH was elevated following the sprint (change in GH: 17.0 ± 14.2 µg l–1; integrated GH: 662 ± 582 min µg l–1). Performance characteristics, the metabolic response to exercise and BMI were not significant predictors of the GH response to exercise. However, age emerged as a significant predictor of both integrated GH (β = –0.547, p = 0.003) and change in GH (β = –0.448, p = 0.019) after the sprint. Conclusion:In non-obese young men, age is a more important predictor of GH following sprint exercise than BMI, sprint performance or the metabolic response to sprint exercise.
Telomere Shortening and Haemodialysis
Authors: Boxall Mark C. , Goodship Timothy H.J. , Brown Alison L. , Ward Michael C. , von Zglinicki Thomas
Published: December 2005

Background: Increased oxidative stress is a well described feature of haemodialysis (HD). This is secondary to an increase in the production of reactive oxygen species and impaired antioxidant mechanisms. Telomeres are the specialized ends of eukaryotic chromosomes and consist of tandemly repeated DNA sequences. Telomeres shorten with each cell division and it is well known that telomere length in peripheral blood mononuclear cells (PBMCs) decreases with age. Telomere shortening rate is increased by oxidative stress. In this study we have examined a possible relationship between oxidative stress and telomere shortening in haemodialysis. Methods: 20 control subjects, 20 non-diabetic and 18 diabetic HD patients were studied. Peripheral blood mononuclear cell telomere length, plasma malondialdehyde plus 4-hydroxyalkenal (MDA+4-HAE) concentration (a marker of oxidative stress) and C-reactive protein (CRP) concentration were measured. Results: MDA+4-HAE and CRP were significantly higher in the HD patients (CRP, controls 7.5 ± 1.5, HD patients 16.4 ± 3.1 mg/l, p < 0.05). There was no difference in mean telomere length between the HD patients and controls (control, 8,283 ± 179 bp; non-diabetic HD, 7,966 ± 160 bp; diabetic HD, 8,033 ± 197 bp) but age adjusted residual telomere length was inversely associated with the length of time on dialysis (r = –0.35, p = 0.03). Conclusion: These results suggest that length of time on dialysis is independently associated with increased telomere shortening in HD patients. We hypothesise that this reflects cumulative DNA exposure to oxidative stress.
Reduced Cytokine Induction and Removal of Complement Products with Synthetic Hemodialysis Membranes
Authors: Schindler Ralf , Ertl Thomas , Beck Werner , Lepenies Julia , Boenisch Olaf , Oppermann Martin , Kaspar Eva , Frei Ulrich
Published: December 2005

The increasing use of high-flux membranes for hemodialysis (HD) has raised concerns that these membranes may confer a higher risk of exposure to cytokine-inducing, bacterial substances (CIS) in the dialysate. Several studies, however, reported higher transfer of CIS through low-flux cellulosic than high-flux synthetic membranes. This surprising paradox was explained by adsorption of CIS to certain high-flux membranes. In order to investigate flux and membrane type independently, we studied two synthetic Polyflux (PF) membranes of the same type but with different flux properties and compared them to a cellulosic membrane (Cuprophan). Three different approaches were employed: (1) cytokine induction in whole blood during in vitro HD contaminated with bacterial filtrates, (2) removal of recombinant C5a, and (3) transfer of purified lipopolysaccharide (LPS). After 90 min recirculation of whole blood, the appearance of IL-6-inducing substances on the blood side was lowest with high-flux PF (1.1 ± 0.2 ng/ml), slightly higher with low-flux PF (1.9 ± 0.7 ng/ml) and highest with Cuprophan (4.1 ± 1 ng/ml). Recombinant C5a added to plasma on the blood side was markedly removed by high-flux PF (by 83%), to a lesser degree and only in the presence of ultrafiltration with low-flux PF (by 54%) and not significantly with Cuprophan (by 11%). Significant transfer of purified LPS from the dialysate onto the blood side was only observed with the cellulosic membrane. We conclude that in contrast to cellulosic membranes, certain synthetic membranes do not permit transfer of LPS. Cytokine induction on the blood side is further reduced by the use of high-flux membranes due to removal of activated complement factors.
Hypoxaemia in Acute Stroke Is Frequent and Worsens Outcome
Authors: Rowat Anne M. , Dennis Martin S. , Wardlaw Joanna M.
Published: December 2005

Background: Hypoxaemia in the acute phase of stroke might damage the ischaemic penumbra and worsen clinical outcome. We determined the frequency of hypoxaemia on admission with stroke and assessed whether it was related to outcome. Methods: We measured arterial oxygen saturation (SaO2) and breathing effort with portable monitoring equipment in a large cohort of acute stroke patients, continually from arrival at hospital, during interdepartment transfer, in imaging and on the ward. Patients received best medical care according to current guidelines. Baseline neurological examination and 3-month outcome (Modified Rankin Scale) were assessed blind to other data. Hypoxaemia was defined as SaO2 <90% for ≧10% of each assessment stage. Results: Mean SaO2 was lowest during transfers (p < 0.01), but hypoxaemia was common in all assessment stages. Patients with hypoxaemia (30/153, 20%) were more likely to have a pre-existing respiratory disease on admission than those without hypoxaemia (p < 0.04). More patients with hypoxaemia (40%) died than those without hypoxaemia (20%) (hazard ratio, 2.0; 95% CI, 1.0–4.1), though after adjusting for National Institute of Health Stroke Scale and age this association was not statistically significant (hazard ratio, 1.5; 95% CI, 0.7–3.1). There were similar numbers of dependent survivors in both groups. Conclusion: Hypoxaemia during acute stroke assessment was associated with increased risk of death. Although SaO2 is lower during transfers, hypoxaemia occurs in all stages of the admission process. Further research is necessary to determine whether strategies to avoid hypoxaemia during acute assessment improve stroke survival.
Consistency of the Benefits of Stroke Units over Years of Operation: An 8-Year Effectiveness Analysis
Authors: Fuentes Blanca , Díez-Tejedor Exuperio , Ortega-Casarrubios M. Angeles , Martínez Patricia , Lara Manuel , Frank Ana
Published: December 2005

Background: The efficacy of stroke units (SU) has been amply demonstrated in randomised trials. However, no long-term studies analysed their effectiveness in daily practice over several years of operation. Methods: Observational study from the stroke data bank of our neurology ward that includes consecutive stroke patients hospitalised since the SU was established in 1995 until the year 2002 (8 years). Clinical effectiveness was analysed in terms of mortality on day 7, in-hospital mortality, functional state at discharge, length of stay, in-hospital complications and long-term hospitalisation rates on a yearly basis using for comparisons χ2 or Student t tests between the first and last 4 years of SU operation. Case-mix adjustments for baseline imbalances and stepwise multivariate logistic regression were also performed for comparative purposes. Results: 3,986 consecutive in-patients were included. No significant differences in the proportion of independent patients at discharge (73.9 vs. 74.5%; n.s.), length of stay (11.2 vs. 11.3 days; n.s.), in-hospital complications (25.0 vs. 25.9%; n.s.) or long-stay hospitalisation (6.3 vs. 6.4%; n.s.) were found comparing the first and last 4 years of SU operation. No significant differences in in-hospital mortality were found after adjustment by case-mix and length of stay. Conclusions: SU effectiveness, in terms of length of stay, death or dependence and long-term hospitalisation, is sustained over the period of operation.
Cerebrovascular Reactivity to L-Arginine in Patients with Lacunar Infarctions
Authors: Pretnar-Oblak Janja , Zaletel Marjan , Zvan Bojana , Sabovic Miso , Pogacnik Tomaz
Published: December 2005

Background: It is well known that endothelial dysfunction plays an important role in the pathogenesis of many cardiovascular disorders. The aim of this study was to test the hypothesis that specific, marked endothelial dysfunction of cerebral arteries is present in patients with lacunar cerebral infarctions. Methods: Cerebrovascular reactivity to L-arginine, which reveals the function of the cerebral endothelium, was investigated in patients with lacunar infarctions (20 patients, 11 male and 9 female, aged 60.9 ± 7.3 years), 21 age- and gender-matched asymptomatic patients with similar cardiovascular risk factors (all patients had arterial hypertension) and 21 age- and gender-matched healthy controls. The mean arterial velocity (vm) in both middle cerebral arteries was measured by transcranial Doppler sonography during a 15-min baseline period, a 30-min intravenous infusion of L-arginine and a 15-min interval after L-arginine infusion. Arterial blood pressure, heart rate and CO2 were measured continuously. Results: The measured vm increase during L-arginine infusion in the patients with lacunar infarctions (13.4 ± 9.1%) was significantly lower compared to the healthy controls (20.5 ± 9.9%) but similar to that obtained in the patients with cardiovascular risk factors (11.5 ± 8.9%). Conclusions: Our results showed that cerebrovascular reactivity to L-arginine, which demonstrates cerebral endothelial function, is significantly impaired in patients with cardiovascular risk factors. Importantly, we found that patients with lacunar infarctions do not show any additional impairment of cerebral endothelial function.
Optical Coherence Tomography of Intraocular Lens Implants and Their Relationship to the Posterior Capsule: A Pilot Study Comparing a Hydrophobic Acrylic to a Plate-Haptic Silicone Type
Authors: Elgohary M.A. , Chauhan D.S. , Dowler J.G.
Published: December 2005

Background: Optical coherence tomography (OCT) has been used to examine the anterior as well as the posterior segment and can be used to examine the intraocular lens (IOL) and their relationship to the posterior capsule in vivo. Objectives: To use OCT to examine two of the IOLs and some of the features related to the development of posterior capsular opacification (PCO). Methods: This is a pilot study of a prospective (n = 12) and a retrospective (n = 14) series of patients who had uneventful phacoemulsification and IOL implantation of either hydrophobic acrylic (Acrysof; Alcon) or plate-haptic (PH) silicone (C11UB; Chiron, Bausch & Lomb) IOLs. The outcome of interest was the ability of OCT to clearly delineate the outline of the IOL optics and their appositional relationship to the posterior capsule. Results: OCT showed that hydrophobic acrylic IOLs had a better defined outline than PH silicone IOLs. It also showed close apposition between hydrophobic acrylic optics and the mid-peripheral part of the posterior capsule and the absence thereof with PH silicone IOLs. Conclusions: Hydrophobic acrylic implants have better definition on the OCT scans than PH silicone and they develop close apposition to the posterior capsule. The latter feature is consistent with the ‘no space, no cell, no PCO’ concept and what is known about the effect of the implant material and design on the rate of PCO.
Sildenafil Improves Dynamic Vascular Function in the Brain: Studies in Patients with Pulmonary Hypertension
Authors: Rosengarten B. , Schermuly R.T. , Voswinckel R. , Kohstall M.G. , Olschewski H. , Weissmann N. , Seeger W. , Kaps M. , Grimminger F. , Ghofrani H.A.
Published: December 2005

Background: Prostaglandins and nitric oxide play a pivotal role in the regulation of macro- and microcirculatory blood flow distribution. Interference with both mediator systems have been implicated in cerebrovascular dysfunction. Inhaled iloprost (long-acting prostacyclin analogue) and the phosphodiesterase-5 inhibitor sildenafil have recently shown efficacy in the treatment of chronic pulmonary hypertension. We investigated the impact of these agents on cerebral microcirculatory regulation in patients suffering from this disease. Methods: In 11 patients suffering from severe pulmonary hypertension, a functional transcranial Doppler test utilizing a visual stimulation paradigm was undertaken to measure the evoked flow velocity in the posterior cerebral artery. Measurements were performed in parallel to right heart catheterization and pharmacological testing of the pulmonary vasoreactivity. After assessment of baseline measurements, inhaled iloprost and oral sildenafil were given consecutively for testing of cerebral and pulmonary vascular function. The data gained from the Doppler measurements were compared to data from 22 healthy volunteers. Results: Both substances provoked a significant reduction of pulmonary arterial pressure and vascular resistance, accompanied by minor changes in systemic vascular resistance. In contrast to these superimposable hemodynamic profiles opposite effects were observed regarding cerebral vascular tone: cerebral microvascular reactivity, as assessed by attenuation and time rate parameters, was significantly improved by sildenafil, but slightly worsened by iloprost. Conclusions: Sildenafil has beneficial effects on cerebral vascular reactivity indicative of an improvement in neurovascular coupling in patients with pulmonary hypertension. These results warrant further investigations of the influence of sildenafil on dynamic vascular function in the brain independent of the underlying disease.
Extracellular ATP Stimulates NO Production in Rat Thick Ascending Limb
Authors: Silva Guillermo , Beierwaltes William H. , Garvin Jeffrey L.
Published: December 2005

NO produced by NO synthase (NOS) 3 acts as an autacoid to regulate NaCl absorption in the thick ascending limb. ATP induces NO production by NOS 3 in endothelial cells. We hypothesized that extracellular ATP activates NOS in thick ascending limbs through P2 receptors. To test this, we measured intracellular NO production using the NO-selective fluorescent dye DAF-2 in suspensions of rat medullary thick ascending limbs. We found that ATP increased DAF-2 fluorescence in a concentration-dependent manner, reaching saturation at &200 μmol/L with an EC50of 37 μmol/L. The increase was blunted by 74% by the nonselective NOS inhibitorl-ω-nitro-arginine-methyl-ester (2 mmol/L; 60±7 versus 16±6 arbitrary fluorescence units;P<0.02;n=5). In the presence of the P2 receptor antagonist suramin (300 μmol/L), ATP-induced NO production was reduced by 64% (101±11 versus 37±5 arbitrary fluorescence units;P<0.002;n=5). Blocking ATP hydrolysis with a 5′-ectonucleotidase inhibitor, ARL67156 (30 μmol/L) enhanced the response to ATP and shifted the EC50to 0.8 μmol/L. In the presence of ARL67156, the EC50of the P2X-selective agonist β,γ-methylene-adenosine 5′-triphosphate was 4.8 μmol/L and the EC50for the P2Y–selective agonist UTP was 40.4 μmol/L. The maximal responses for both agonists were similar. Taken together, these data indicate that ATP stimulates NO production in the thick ascending limb primarily through P2X receptor activation and that ATP hydrolysis may regulate NO production.
Activation of AMP-Activated Protein Kinase Enhances Angiotensin II–Induced Proliferation in Cardiac Fibroblasts
Authors: Hattori Yoshiyuki , Akimoto Kazumi , Nishikimi Toshio , Matsuoka Hiroaki , Kasai Kikuo
Published: December 2005

AMP-activated kinase (AMPK) is a highly conserved heterotrimeric kinase that functions as a metabolic regulator of cellular enzymes involved in carbohydrate and fat metabolism, which regulate ATP conservation and synthesis. Here, we investigated whether AMPK signaling has a role in the regulation of angiotensin II (Ang II)–induced proliferation in rat cardiac fibroblasts. Aminoimidazole-4-carboxamide-1-β-ribofuranoside (AICAR) activated AMPK in rat cardiac fibroblasts and increased Ang II–induced extracellular signal–regulated kinase 1/2 phosphorylation and activity. AICAR also increased Ang II–induced c-fos mRNA expression in the cells. [
3
H]-thymidine and [
3
H]-proline incorporation by cardiac fibroblasts treated with Ang II was enhanced when the cells were pretreated with AICAR. Inhibition of AMPK by small interfering RNA for AMPKα1 suppressed Ang II–induced extracellular signal–regulated kinase activity, c-fos mRNA expression, and cell proliferation. Treatment of rats with AICAR (1 mg/g body weight per day) for 1 week significantly enhanced Ang II–induced hypertrophy of the myocardium. Our findings indicate that AMPK works as a stimulator of the Ang II–induced proliferative pathway in cardiac fibroblasts. Inhibition of AMPK signaling might serve as a new therapeutic target of remodeling of the hypertrophic myocardium.
Angiotensin-II Type 1 Receptor–Mediated Hypertension in D
4
Dopamine Receptor–Deficient Mice
Authors: Bek Martin J. , Wang Xiaoyan , Asico Laureano D. , Jones John E. , Zheng Shaopeng , Li XiaoXi , Eisner Gilbert M. , Grandy David K. , Carey Robert M. , Soares-da-Silva Patricio , Jose Pedro A.
Published: December 2005

Dopamine receptors are important in systemic blood pressure regulation. D
4
receptors are expressed in the kidney and brain, but their role in cardiovascular regulation is unknown. In pentobarbital-anesthetized mice, systolic and diastolic blood pressures were elevated in sixth-generation D
4
receptor–deficient (D
4
−/−
) mice and in tenth-generation D
4
−/−
mice compared with D
4
wild-type (D
4
+/+
) littermates. The conscious blood pressures measured via a chronic arterial (femoral) catheter or telemetry (carotid) were also higher in D
4
−/−
mice than in D
4
littermates. Basal renal and plasma renin concentrations were similar in the 2 mouse strains. The protein expression of angiotensin II type 1 receptor was increased in homogenates of kidney (330±53%, n=5) and brain (272±69%, n=5) of D
4
−/−
mice relative to D
4
+/+
mice (kidney: 100±12%, n=5; brain: 100±32%, n=5). The expression of the receptor in renal membrane was also increased in D
4
−/−
mice (289±28%, n=8) relative to D
4
+/+
mice (100±14%, n=10). In contrast, the expression in the heart was similar in the 2 strains. Bolus intravenous injection of angiotensin II type 1 receptor antagonist losartan initially decreased mean arterial pressures to a similar degree in D
4
−/−
and D
4
+/+
littermates. However, the hypotensive effect of losartan dissipated after 10 minutes in D
4
+/+
mice, whereas the effect persisted for >45 minutes in D
4
−/−
mice. We conclude that the absence of the D
4
receptor increases blood pressure, possibly via increased angiotensin II type 1 receptor expression.
αV Integrins Are Necessary for Eutrophic Inward Remodeling of Small Arteries in Hypertension
Authors: Heerkens Egidius H.J. , Shaw Linda , Ryding Alisdair , Brooker Gillian , Mullins John J. , Austin Clare , Ohanian Vasken , Heagerty Anthony M.
Published: December 2005

Human essential hypertension is characterized by eutrophic remodeling of small arteries, with little evidence of hypertrophy. Likewise, vessels of young hypertensive TGR(mRen2)27 animals have undergone similar structural alterations. The role of integrins in resistance arteries of TGR(mRen2)27 during the eutrophic-remodeling process was examined as blood pressure rose. Initially, 8 α and 3 β integrins were identified and levels of expression investigated using RT-PCR. As pressure increased and remodeling advanced, integrin expression profiles revealed that only αV was significantly raised. In conjunction, we confirmed elevated integrin αV protein levels in TGR(mRen2)27 rat arteries and localization to the media using immunofluorescence. β1 and β3, but not β5 integrin subunits were coprecipitated with integrin αV and are implicated in the eutrophic remodeling process. Administration of a peptide antagonist of αVβ3 abolished remodeling but enhanced growth, indicating that hypertrophy supervened as a response to hypertension-induced increases in wall stress. We have established that the only upregulated integrin, the αV subunit of integrin αVβ3, has a crucial role in the hypertensive remodeling process of TGR(mRen2)27 rat resistance arteries. During hypertensive remodeling, functions of specific αVβ3-extracellular matrix interactions are likely to allow vascular smooth muscle cell–length autoregulation, which includes a migratory process, to maintain a narrowed lumen after a prolonged constricted state.
Prognostic Significance for Stroke of a Morning Pressor Surge and a Nocturnal Blood Pressure Decline
Authors: Metoki Hirohito , Ohkubo Takayoshi , Kikuya Masahiro , Asayama Kei , Obara Taku , Hashimoto Junichiro , Totsune Kazuhito , Hoshi Haruhisa , Satoh Hiroshi , Imai Yutaka
Published: December 2005

There is continuing controversy over whether the pattern of circadian blood pressure (BP) variation that includes a nocturnal decline in BP and a morning pressor surge has prognostic significance for stroke risk. In this study, we followed the incidence of stroke in 1430 subjects aged ≥40 years in Ohasama, Japan, for an average of 10.4 years. The association between stroke risk and the pattern of circadian BP variation was analyzed with a Cox proportional hazards model after adjustment for possible confounding factors. There was no significant association between total stroke risk and the nocturnal decline in BP (percentage decline from diurnal level) or between total stroke risk and the morning pressor surge. The cerebral infarction risk was significantly higher in subjects with a <10% nocturnal decline in BP as compared with subjects who had a ≥10% nocturnal decline in BP (
P
=0.04). The morning pressor surge was not associated with a risk of cerebral infarction. On the other hand, an increased risk of cerebral hemorrhage was observed in subjects with a large morning pressor surge (≥25 mm Hg;
P
=0.04). Intracerebral hemorrhage was also observed more frequently in extreme dippers (those with a ≥20% nocturnal decline in BP) than dippers (those with a 10% to 19% decline;
P
=0.02). A disturbed nocturnal decline in BP is associated with cerebral infarction, whereas a large morning pressor surge and a large nocturnal decline in BP, which are analogous to a large diurnal increase in BP, are both associated with cerebral hemorrhage.
Knockdown of Arginase I Restores NO Signaling in the Vasculature of Old Rats
Authors: White Anthony R. , Ryoo Sungwoo , Li Dechun , Champion Hunter C. , Steppan Jochen , Wang Danming , Nyhan Daniel , Shoukas Artin A. , Hare Joshua M. , Berkowitz Dan E.
Published: December 2005

Arginase, expressed in endothelial cells and upregulated in aging blood vessels, competes with NO synthase (NOS) forl-arginine, thus modulating vasoreactivity and attenuating NO signaling. Moreover, arginase inhibition restores endothelial NOS signaling andl-arginine responsiveness in old rat aorta. The arginase isoform responsible for modulating NOS, however, remains unknown. Because isoform-specific arginase inhibitors are unavailable, we used an antisense (AS) oligonucleotide approach to knockdown arginase I (Arg I). Western blot and quantitative PCR confirmed that Arg I is the predominant isoform expressed in endothelialized aortic rings and is upregulated in old rats compared with young. Aortic rings from 22-month-old rats were incubated for 24 hours with sense (S), AS oligonucleotides, or medium alone (C). Immunohistochemistry, immunoblotting, and enzyme assay confirmed a significant knockdown of Arg I protein and arginase activity in AS but not S or C rings. Conversely, calcium-dependent NOS activity and vascular metabolites of NO was increased in AS versus S or C rings. Acetylcholine (endothelial-dependent) vasorelaxant responses were enhanced in AS versus S or C treated rings. In addition, 1H-oxadiazolo quinoxalin-1-one (10 μmol/L), a soluble guanylyl cyclase inhibitor, increased the phenylephrine response in AS compared with S and C rings suggesting increased NO bioavailability. Finally,l-arginine (0.1 mmol/L)-induced relaxation was increased in AS versus C rings. These data support our hypothesis that Arg I plays a critical role in the pathobiology of age-related endothelial dysfunction. AS oligonucleotides may, therefore, represent a novel therapeutic strategy against age-related vascular endothelial dysfunction.
Risk Factors for Arterial Hypertension in Adults With Initial Optimal Blood Pressure
Authors: de Simone Giovanni , Devereux Richard B. , Chinali Marcello , Roman Mary J. , Best Lyle G. , Welty Thomas K. , Lee Elisa T. , Howard Barbara V.
Published: December 2005

Whether metabolic factors and their change over time influence development of arterial hypertension in adults with initially optimal blood pressure (BP) is unknown. We analyzed associations of BP in the optimal range (<120/80 mm Hg), metabolic risk factors, and their changes over 4-year follow-up, with 8-year incident hypertension, in a cohort of American Indians with a high prevalence of obesity. At baseline, 967 participants with optimal BP and no prevalent cardiovascular disease (69.5% women; mean age, 54±7 years) were evaluated and reexamined after 4 (second examination) and 8 years to evaluate predictors of 8-year incident arterial hypertension. In participants with normal glucose tolerance, baseline BP and decrease in high-density lipoprotein cholesterol from baseline to the second examination were the most potent predictors of 8-year arterial hypertension (both
P
<0.0001), with additional effects of baseline waist circumference and its increase, increase in BP, and presence of diabetes at the second examination (all
P
<0.04). In participants with impaired glucose tolerance or diabetes, the most potent predictor of 8-year incident hypertension was diabetes at the second examination (
P
<0.0001) followed by a increase in BP and LDL cholesterol over the first 4 years (both
P
<0.001). Thus, incident arterial hypertension can be predicted by initial metabolic profile and unfavorable metabolic variations over time, in addition to initial BP. At optimal levels of initial BP, increasing abdominal obesity, and abnormal lipid profile are major predictors of development of arterial hypertension. Possible implications of these findings for primary cardiovascular prevention should be tested in prospective studies.
Weather-Related Changes in 24-Hour Blood Pressure Profile
Authors: Modesti Pietro Amedeo , Morabito Marco , Bertolozzi Iacopo , Massetti Luciano , Panci Gabriele , Lumachi Camilla , Giglio Alessia , Bilo Grzegorz , Caldara Gianluca , Lonati Laura , Orlandini Simone , Maracchi Giampiero , Mancia Giuseppe , Gensini Gian Franco , Parati Gianfranco
Published: December 2005

A downward titration of antihypertensive drug regimens in summertime is often performed on the basis of seasonal variations of clinic blood pressure (BP). However, little is known about the actual interaction between outdoor air temperature and the effects of antihypertensive treatment on ambulatory BP. The combined effects of aging, treatment, and daily mean temperature on clinic and ambulatory BP were investigated in 6404 subjects referred to our units between October 1999 and December 2003. Office and mean 24-hour systolic BP, as well as morning pressure surge, were significantly lower in hot (>90th percentiles of air temperature; 136±19, 130±14, and 33.3±16.1 mm Hg;
P
<0.05 for all), and higher in cold (<10th percentiles) days (141±12, 133±11, and 37.3±9.5 mm Hg; at least
P
<0.05 for all) when compared with intermediate days (138±18, 132±14, and 35.3±15.4 mm Hg). At regression analysis, 24-hour and daytime systolic pressure were inversely related to temperature (
P
<0.01 for all). Conversely, nighttime systolic pressure was positively related to temperature (
P
<0.02), with hot days being associated with higher nighttime pressure. Air temperature was identified as an independent predictor of nighttime systolic pressure increase in the group of elderly treated hypertensive subjects only. No significant relationship was found between air temperature and heart rate. Our results show for the first time that hot weather is associated with an increase in systolic pressure at night in treated elderly hypertensive subjects. This may be because of a nocturnal BP escape from the effects of a lighter summertime drug regimen and may have important implications for seasonal modulation of antihypertensive treatment.
2-Methoxyestradiol Induces Cell Cycle Arrest and Mitotic Cell Apoptosis in Human Vascular Smooth Muscle Cells
Authors: Gui Yu , Zheng Xi-Long
Published: December 2005

It has been shown that 2-methoxyestradiol (2-ME) inhibits cell proliferation and DNA synthesis in human aortic smooth muscle cells. However, the cellular mechanisms underlying the antiproliferative activity of 2-ME are unclear. The present study was performed to explore the cellular mechanisms whereby 2-ME leads to growth inhibition and apoptosis of human smooth muscle cells. Our results demonstrate that at 1 hour of treatment, 1 μmol/L 2-ME induces multiple spindles, overamplified centrosomes, and multipolar cytokinesis, whereas 10 μmol/L 2-ME causes completely damaged spindle, disorientated centrosomes, and missegregated chromosomes. At 6 hours of treatment, the mitotic index was increased and reached a maximal level, and cells with 4N DNA content (4N cells) began to accumulate. The increased mitotic cells induced by 2-ME were apoptotic as detected by both annexin V and TUNEL staining. Blockage of cells in G
1/0
phase by thymidine prevented 2-ME-induced apoptosis. In addition, the increased mitotic index declined concurrently when even more 4N cells accumulated at 12 to 48 hours of treatment with 10 μmol/L 2-ME. Furthermore, in response to 2-ME, cells delayed entry into the next cell cycle and exhibited aneuploidy or micronuclei. Some aneuploidy cells continued to synthesize DNA. We conclude that 2-ME treatment not only arrests cells in mitosis and promotes mitotic cell apoptosis, but also causes cells to undergo “mitotic slippage” and endoreduplication. The induction of mitotic cell arrest and apoptosis may be a major cellular mechanism by which 2-ME inhibits proliferation of human smooth muscle cells.
Uric Acid, Left Ventricular Mass Index, and Risk of Cardiovascular Disease in Essential Hypertension
Authors: Iwashima Yoshio , Horio Takeshi , Kamide Kei , Rakugi Hiromi , Ogihara Toshio , Kawano Yuhei
Published: December 2005

Elevated serum uric acid (UA) is frequently encountered in individuals with hypertension, but whether the relationship between UA and cardiovascular events is circumstantial or causal remains to be answered. We examined the association between serum UA and left ventricular mass index (LVMI) and investigated prospectively whether the combination of UA and LVMI can predict the incidence of cardiovascular disease (CVD) in asymptomatic subjects with essential hypertension. A total of 619 subjects (mean age, 61 years; 52% female) free of prior CVD were included in this study. A significant association between UA and LVMI was also confirmed in multiple regression analysis (male: F=4.29,
P
<0.04; female: F=4.24,
P
<0.05). During follow-up (mean, 34 months), 28 subjects (14 female) developed CVD including myocardial infarction, angina pectoris, congestive heart failure, cerebral infarction, and transient cerebral ischemia. Sex-specific median values were used to separate the higher group from the lower group of UA and LVMI. Kaplan–Meier curves showed a significantly poorer survival rate in the group with higher UA and LVMI (LVMI, male: >126.9, female: >112.0 g/m
2
; UA, male: >374.7, female: >303.3 μmol/L; log-rank χ
2
=13.18;
P
<0.01). Multivariate Cox regression analysis showed that the combination of higher UA and LVMI was an independent predictor for CVD events (hazard ratio, 2.38;
P
<0.03). Our findings demonstrate that UA is independently associated with LVMI and suggest that the combination of hyperuricemia combined with left ventricular hypertrophy is an independent and powerful predictor for CVD. The association between UA and CVD events may be introduced in part because of a direct association of UA with LVMI.
Time Course of Maternal Plasma Volume and Hormonal Changes in Women With Preeclampsia or Fetal Growth Restriction
Authors: Salas Sofía P. , Marshall Guillermo , Gutiérrez Blanca L. , Rosso Pedro
Published: December 2005

We tested the hypothesis that women with idiopathic fetal growth restriction (FGR) or preeclampsia (PE) have lower concentrations of some water-retaining hormones, such as aldosterone and estradiol, either preceding or concomitant with the onset of the reduced plasma volume described in these women. Plasma volume and serum concentrations of estradiol, progesterone, and aldosterone were measured serially at monthly intervals in 135 pregnant women from week 10 until term. Twenty-three developed idiopathic FGR, 17 had PE, and 95 remained normotensive and delivered normal-size infants (controls). Changes over time for each variable were studied using mixed models. Maternal age, parity, and weight/height at term were similar in all of the groups. Birth weight, body length, and ponderal index were lower in FGR and PE than in controls. Plasma volume increased throughout pregnancy in controls but was lower in FGR and PE from week 14 to 17 until term. Aldosterone values were lower in PE from week 26 to 29 onwards and in FGR after week 34. Progesterone concentrations were higher in PE than either control or FGR from week 18 to 21 until term. In contrast, FGR pregnancies had reduced progesterone and estradiol concentrations after week 34. Progesterone:estradiol ratio was significantly higher only in the PE group. In mothers with idiopathic FGR or PE, less expansion in plasma volume occurred before alterations in hormonal concentrations. We speculate that the early rise in progesterone may have a pathogenic role in the development of preeclampsia.
Adenovirus-Mediated Small-Interference RNA for In Vivo Silencing of Angiotensin AT1aReceptors in Mouse Brain
Authors: Chen Yanfang , Chen Hao , Hoffmann Andrea , Cool David R. , Diz Debra I. , Chappell Mark C. , Chen Alex , Morris Mariana
Published: December 2005

Because of the lack of pharmacological approaches, molecular genetic methods have been required to differentiate between angiotensin type 1(AT1) receptor subtypes AT1aand AT1b. RNA interference is a new tool for the study of gene function, producing specific downregulation of protein expression. In this study, we used the small hairpin RNA (shRNA) cassette method to screen target sites for selectively silencing AT1aor AT1breceptor subtypes in cultured Neuro-2a cells using real-time RT-PCR. For in vivo functional studies, we used C57BL mice with arterial telemetric probes and computerized licking monitors to test the effect of adenovirus carrying the DNA sequence coding AT1ashRNA (Ad-AT1a-shRNA). Ad-AT1a-shRNA was injected into the lateral ventricle (intracerebroventricular) or the brain stem nucleus tractus solitaries/dorsal vagal nucleus (NTS/DVN) with measurement of water intake, blood pressure (BP), and heart rate (HR) for up to 20 days after injection. Tissue culture studies verified the specificity and the efficiency of the constructs. In animal studies, β-galactosidase staining and Ang receptor binding assays showed expression of shRNA and downregulation of Ang AT1receptors in the subfornical organ and NTS/DVN by >70%. Intracerebroventricular injection of Ad-AT1a-shRNA increased water intake with no effect on BP or HR. In contrast, microinjection of Ad-AT1a-shRNA into NTS/DVN caused a decrease in BP with no effect on HR or water intake. Results demonstrate the use of the RNA interference method in site-directed silencing of gene expression and provide a method for the in vivo study of Ang AT1receptor function.
Comparison of Electrode Cooling Between Internal and Open Irrigation in Radiofrequency Ablation Lesion Depth and Incidence of Thrombus and Steam Pop
Authors: Yokoyama Katsuaki , Nakagawa Hiroshi , Wittkampf Fred H.M. , Pitha Jan V. , Lazzara Ralph , Jackman Warren M.
Published: December 2005

Background—

Electrode cooling by circulating fluid within the electrode (closed loop) or open irrigation facilitates radiofrequency (RF) ablation. This study compared lesion parameters between closed loop and open irrigation with the use of a canine model.

Methods and Results—

In 8 anesthetized dogs, the skin over the thigh muscle was incised and raised, forming a cradle superfused with heparinized blood (activated clotting time >350 seconds) at 37°C. A 7F 4-mm closed loop electrode (irrigation 36 mL/min) and 7.5F 3.5-mm open irrigation electrode (irrigation 17 mL/min) were positioned perpendicular to the thigh muscle at 10 g contact weight. RF was applied (n=121) at 20 or 30 W for 60 seconds in low (0.1 m/s) or high (0.5 m/s) pulsatile blood flow. Temperatures were measured in the electrode, electrode-tissue interface, and within the tissue at 3- and 7-mm depths. After each RF, the cradle was emptied to examine the electrode and interface for thrombus. There was no difference between closed loop and open irrigation in impedance, lesion depth, or tissue temperature at 20 or 30 W. Interface temperature and electrode temperature were greater in the closed loop application. Thrombus occurred in 32 of 63 closed loop versus 0 of 58 open irrigation RF applications (
P
<0.05) with interface temperature ≥80°C in all 32 (electrode temperature <40°C in 1, 40°C to 50°C in 26, and >50°C in 5). With closed loop, interface temperature and thrombus incidence were greater at 30 W and low blood flow. With open irrigation, interface temperature remained low (≤71°C) with no difference between 20 and 30 W or between low and high blood flow. Steam pop occurred at 20 W in 4 of 35 closed loop and 0 of 30 open irrigation and at 30 W in 15 of 28 closed loop and 4 of 28 open irrigation applications (
P
<0.05).

Conclusions—

Lower interface temperature, thrombus, and steam pop, especially in low blood flow, indicate greater interface cooling with open irrigation.