bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biphasic Time Course of the Changes in Aldosterone Biosynthesis Under High-Salt Conditions in Dahl Salt-Sensitive Rats
Authors: Morizane Shintaro , Mitani Fumiko , Ozawa Kae , Ito Kentaro , Matsuhashi Tomohiro , Katsumata Yoshinori , Ito Hideyuki , Yan Xiaoxiang , Shinmura Ken , Nishiyama Akira , Honma Seijiro , Suzuki Takeshi , Funder John W. , Fukuda Keiichi , Sano Motoaki 
Published: March 2012

Objective—
The comorbidity of excess salt and elevated plasma aldosterone has deleterious effects in cardiovascular disease. We evaluated the mechanisms behind the paradoxical increase in aldosterone biosynthesis in relation to dietary intake of salt.

Methods and Results—

Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats were fed a high-salt diet, and plasma and tissue levels of aldosterone in the adrenal gland and heart were quantified by liquid chromatography–electrospray ionization–tandem mass spectrometry. In Dahl-S rats, we found that the delayed and paradoxical increase in aldosterone biosynthesis after the initial and appropriate response to high salt. The late rise in aldosterone biosynthesis was accompanied by upregulation of CYP11B2 expression in the zona glomerulosa and increased adrenal angiotensin II levels and renin-angiotensin system components. It preceded the appearance of left ventricular systolic dysfunction and renal insufficiency. Blockade of angiotensin AT
1
receptors reversed the paradoxical increase in aldosterone biosynthesis. In contrast, Dahl-R rats maintained the initial suppression of aldosterone biosynthesis. Aldosterone levels in the heart closely paralleled those in the plasma and adrenal gland and disappeared after bilateral adrenalectomy.

Conclusion—
Chronic salt overload in Dahl-S rats stimulates aberrant aldosterone production via activation of the local renin-angiotensin system in the adrenal gland, thereby creating the comorbidity of excess salt and elevated plasma aldosterone.
Kv1.3 Channels Can Modulate Cell Proliferation During Phenotypic Switch by an Ion-Flux Independent Mechanism
Authors: Cidad Pilar , Jiménez-Pérez Laura , García-Arribas Daniel , Miguel-Velado Eduardo , Tajada Sendoa , Ruiz-McDavitt Christian , López-López José R. , Pérez-García M. Teresa 
Published: March 2012

Objective—
Phenotypic modulation of vascular smooth muscle cells has been associated with a decreased expression of all voltage-dependent potassium channel (Kv)1 channel encoding genes but Kcna3 (which encodes Kv1.3 channels). In fact, upregulation of Kv1.3 currents seems to be important to modulate proliferation of mice femoral vascular smooth muscle cells in culture. This study was designed to explore if these changes in Kv1 expression pattern constituted a landmark of phenotypic modulation across vascular beds and to investigate the mechanisms involved in the proproliferative function of Kv1.3 channels.

Methods and Results—
Changes in Kv1.3 and Kv1.5 channel expression were reproduced in mesenteric and aortic vascular smooth muscle cells, and their correlate with protein expression was electrophysiologicaly confirmed using selective blockers. Heterologous expression of Kv1.3 and Kv1.5 channels in HEK cells has opposite effects on the proliferation rate. The proproliferative effect of Kv1.3 channels was reproduced by “poreless” mutants but disappeared when voltage-dependence of gating was suppressed.

Conclusion—
These findings suggest that the signaling cascade linking Kv1.3 functional expression to cell proliferation is activated by the voltage-dependent conformational change of the channels without needing ion conduction. Additionally, the conserved upregulation of Kv1.3 on phenotypic modulation in several vascular beds makes this channel a good target to control unwanted vascular remodeling.
Transition From Obesity to Metabolic Syndrome Is Associated With Altered Myocardial Autophagy and Apoptosis
Authors: Li Zi-Lun , Woollard John R. , Ebrahimi Behzad , Crane John A. , Jordan Kyra L. , Lerman Amir , Wang Shen-Ming , Lerman Lilach O. 
Published: March 2012

Objective—
Transition from obesity to metabolic-syndrome (MetS) promotes cardiovascular diseases, but the underlying cardiac pathophysiological mechanisms are incompletely understood. We tested the hypothesis that development of insulin resistance and MetS is associated with impaired myocardial cellular turnover.

Methods and Results—
MetS-prone Ossabaw pigs were randomized to 10 weeks of standard chow (lean) or to 10 (obese) or 14 (MetS) weeks of atherogenic diet (n=6 each). Cardiac structure, function, and myocardial oxygenation were assessed by multidetector computed-tomography and Blood Oxygen Level-Dependent–MRI, the microcirculation with microcomputed-tomography, and injury mechanisms by immunoblotting and histology. Both obese and MetS showed obesity and dyslipidemia, whereas only MetS showed insulin resistance. Cardiac output and myocardial perfusion increased only in MetS, yet Blood Oxygen Level-Dependent–MRI showed hypoxia. Inflammation, oxidative stress, mitochondrial dysfunction, and fibrosis also increased in both obese and MetS, but more pronouncedly in MetS. Furthermore, autophagy in MetS was decreased and accompanied by marked apoptosis.

Conclusion—
Development of insulin resistance characterizing a transition from obesity to MetS is associated with progressive changes of myocardial autophagy, apoptosis, inflammation, mitochondrial dysfunction, and fibrosis. Restoring myocardial cellular turnover may represent a novel therapeutic target for preserving myocardial structure and function in obesity and MetS.
Targeted Focal Adhesion Kinase Activation in Cardiomyocytes Protects the Heart From Ischemia/Reperfusion Injury
Authors: Cheng Zhaokang , DiMichele Laura A. , Hakim Zeenat S. , Rojas Mauricio , Mack Christopher P. , Taylor Joan M. 
Published: March 2012

Objective—
We previously reported that cardiac-restricted deletion of focal adhesion kinase (FAK) exacerbated myocyte death following ischemia/reperfusion (I/R). Here, we interrogated whether targeted elevation of myocardial FAK activity could protect the heart from I/R injury.

Methods and Results—

Transgenic mice were generated with myocyte-specific expression of a FAK variant (termed SuperFAK) that conferred elevated allosteric activation. FAK activity in unstressed transgenic hearts was modestly elevated, but this had no discernable effect on anabolic heart growth or cardiac function. Importantly, SuperFAK hearts exhibited a dramatic increase in FAK activity and a reduction in myocyte apoptosis and infarct size 24 to 72 hours following I/R. Moreover, serial echocardiography revealed that the transgenic mice were protected from cardiac decompensation for up to 8 weeks following surgery. Mechanistic studies revealed that elevated FAK activity protected cardiomyocytes from I/R-induced apoptosis by enhancing nuclear factor-κB (NF-κB)–dependent survival signaling during the early period of reperfusion (30 and 60 minutes). Moreover, adenoviral-mediated expression of SuperFAK in cultured cardiomyocytes attenuated H
2
O
2
or hypoxia/reoxygenation-induced apoptosis, whereas blockade of the NF-κB pathway using a pharmacological inhibitor or small interfering RNAs completely abolished the beneficial effect of SuperFAK.

Conclusion—
Enhancing cardiac FAK activity attenuates I/R-induced myocyte apoptosis through activation of the prosurvival NF-κB pathway and may represent a novel therapeutic strategy for ischemic heart diseases.
Fibrin D-Dimer, Tissue-Type Plasminogen Activator, von Willebrand Factor, and Risk of Incident Stroke in Older Men
Authors: Wannamethee S. Goya , Whincup Peter H. , Lennon Lucy , Rumley Ann , Lowe Gordon D. 
Published: March 2012

Background and Purposes—
Abnormalities in blood coagulation and the fibrinolytic system have been associated with increased risk of stroke, but few prospective studies have studied the associations in older adults. We have examined the associations between fibrin D-dimer, tissue-type plasminogen activator, and von Willebrand factor (vWF) and risk of stroke in older men and examined their predictive roles separately in normotensive and hypertensive men.

Methods—
Prospective study of 3358 men aged 60 to 79 years with no previous diagnosis of myocardial infarction or stroke and without atrial fibrillation followed-up for an average of 9 years, during which there were 187 incident stroke events.

Results—

Increased levels of D-dimer and vWF were associated with significantly increased risk of major stroke events after adjustment for potential confounders, including systolic blood pressure (adjusted hazard ratios and 95% confidence interval per standard deviation increase in D-dimer and vWF were 1.24 [95% confidence interval, 1.08–1.44] and 1.25 [95% confidence interval, 1.09–1.45], respectively). No associations were seen with tPA after adjustment. The positive associations between D-dimer and vWF and incident stroke remained after additional adjustment for markers of inflammation (C-reactive protein, IL-6). D-dimer was associated with stroke in both normotensive and hypertensive men; vWF showed stronger associations in normotensive than in hypertensive men (test for interaction:
P
=0.52 for D-dimer;
P
<0.01 for vWF).

Conclusions—
Fibrin D-dimer and vWF are associated with increased risk of stroke in older men. These associations were not explained by their associations with inflammation. D-dimer may be a useful marker to identify those at high risk for stroke among hypertensive men.
Prevalence and Length of Recovery of Pusher Syndrome Based on Cerebral Hemispheric Lesion Side in Patients With Acute Stroke
Authors: Abe Hiroaki , Kondo Takeo , Oouchida Yutaka , Suzukamo Yoshimi , Fujiwara Satoru , Izumi Shin-Ichi 
Published: March 2012

Background and Purpose—
The aim of this study was to determine if side of cerebral hemisphere lesion affects the prevalence and time course of pushing behavior (PB) after stroke.

Methods—
A total of 1660 patients with acute stroke were investigated. PB was assessed using the standardized Scale for Contraversive Pushing. Risk ratios were used to evaluate the differences in the prevalence of PB between right cerebral hemisphere-damaged (RCD) and left cerebral hemisphere-damaged (LCD) patients. The differences in the time course among 35 (27 RCD and 8 LCD) patients were evaluated by analyzing Scale for Contraversive Pushing scores with the Kaplan–Meier method using a log-rank test.

Results—

PB was observed in 156 (9.4%) patients. The prevalence of PB was significantly higher in RCD (97 of 556 [17.4%]) than in LCD (57 of 599 [9.5%]) patients; risk ratio was 1.83 (95% CI, 1.35–2.49). The log-rank test indicated that RCD patients exhibited a significantly slower recovery than LCD patients (
P
=0.027).

Conclusions—
The number of RCD patients who exhibited PB was higher than that of LCD patients. The duration of recovery from PB was longer in RCD patients than in LCD patients.
Factors Affecting Clot Lysis Rates in Patients With Spontaneous Intraventricular Hemorrhage
Authors: Ziai Wendy C. , Muschelli John , Thompson Carol B. , Keyl Penelope M. , Lane Karen , Shao Shuai , Hanley Daniel F. 
Published: March 2012

Background and Purpose—
In the treatment of severe intraventricular hemorrhage (IVH), thrombolytic use and clot size are known to influence clot lysis rates. We evaluated the effect of other variables on IVH clot lysis rates among patients treated with recombinant tissue-type plasminogen activator or placebo.

Methods—
One hundred patients with IVH and intracerebral hemorrhage volume <30 mL requiring emergency external ventricular drainage from 2 multicenter trials were treated with intraventricular administration of recombinant tissue-type plasminogen activator (n=78; 53 males, 25 females) or placebo (n=22; 7 males, 15 females). IVH volume was quantified daily by head CT. A segmented linear regression using an optimized spline knot for each patient was fit. Random effects linear regression was used to estimate the effect of prespecified patient characteristics on clot lysis rates over the first 6 days.

Results—

Stability IVH volumes were larger in males (N=60; 54±5 mL) than females (N=40; 36±5 mL;
P
=0.01). Intraventricular thrombolytic treatment was associated with an increase in clot lysis rate of 14.6% of stability IVH volume/day before the spline knot compared with the placebo group (
P
<0.001). After adjustment for thrombolytic, higher baseline serum plasminogen and lower baseline platelet count were independently associated with an increase in clot lysis of 1.28%/day per 10-g/dL increase (
P
<0.001) and 0.70% /day per 10×10
3
/uL decrease (
P
<0.001) before the knot, respectively.

Conclusions—
Although thrombolysis remains the major determinant of IVH clot lysis rate, higher baseline serum plasminogen and lower platelet count also predict faster clot lysis. Further studies are needed to confirm whether plasminogen availability and thrombus structure impact IVH clot removal.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00650858.
Duration of Diabetes and Risk of Ischemic Stroke
Authors: Banerjee Chirantan , Moon Yeseon P. , Paik Myunghee C. , Rundek Tatjana , Mora-McLaughlin Consuelo , Vieira Julio R. , Sacco Ralph L. , Elkind Mitchell S.V. 
Published: March 2012

Background and Purpose—
Diabetes increases stroke risk, but whether diabetes status immediately before stroke improves prediction and whether duration is important are less clear. We hypothesized that diabetes duration independently predicts ischemic stroke.

Methods—
Among 3298 stroke-free participants in the Northern Manhattan Study, baseline diabetes and age at diagnosis were determined. Incident diabetes was assessed annually (median, 9 years). Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% CI for incident ischemic stroke using baseline diabetes, diabetes as a time-dependent covariate, and duration of diabetes as a time-varying covariate; models were adjusted for demographic and cardiovascular risk factors.

Results—
Mean age was 69±10 years (52% Hispanic, 21% white, and 24% black); 22% had diabetes at baseline and 10% had development of diabetes. There were 244 ischemic strokes, and both baseline diabetes (HR, 2.5; 95% CI, 1.9–3.3) and diabetes considered as a time-dependent covariate (HR, 2.4; 95% CI, 1.8–3.2) were similarly associated with stroke risk. Duration of diabetes was associated with ischemic stroke (adjusted HR, 1.03 per year with diabetes; 95% CI, 1.02–1.04). Compared to nondiabetic participants, those with diabetes for 0 to 5 years (adjusted HR, 1.7; 95% CI, 1.1–2.7), 5 to 10 years (adjusted HR, 1.8; 95% CI, 1.1–3.0), and ≥10 years (adjusted HR, 3.2; 95% CI, 2.4–4.5) were at increased risk.

Conclusions—
Duration of diabetes is independently associated with ischemic stroke risk adjusting for risk factors. The risk increases 3% each year, and triples with diabetes ≥10 years.
High Levels of S100A12 Are Associated With Recent Plaque Symptomatology in Patients With Carotid Atherosclerosis
Authors: Abbas Azhar , Aukrust Pål , Dahl Tuva B. , Bjerkeli Vigdis , Sagen Ellen B. Lund , Michelsen Annika , Russell David , Krohg-Sørensen Kirsten , Holm Sverre , Skjelland Mona , Halvorsen Bente 
Published: March 2012

Background and Purpose—
Atherosclerosis is a progressive chronic disease, in which inflammation plays a key role. The calcium-binding proteins calgranulins including S100A8, S100A9, and S100A12 are involved in many cellular activities and pathological processes including inflammation. We therefore hypothesized that calgranulins may be markers of plaque instability in patients with carotid atherosclerosis.

Methods—
Plasma levels of S100A8/A9 and S100A10 were measured in 159 consecutive patients with high-grade carotid stenosis and in 22 healthy control subjects. The mRNA levels of calgranulins were also measured within the atherosclerotic carotid plaques, and their regulation was analyzed in vitro in monocytes.

Results—
Our main findings were: (1) plasma levels of S100A12 were significantly higher in patients with carotid atherosclerosis compared with healthy control subjects with the highest levels in patients with the most recent symptoms (ie, within 2 months); (2) plasma levels of S100A8/S100A9 showed a modest increase in patients with symptoms in the previous 2 to 6 months but not in the other patients; (3) mRNA levels of S100A8, S100A9, and S100A12 showed increased expression in atherosclerotic carotid plaques from patients with the most recent symptoms compared with the remaining patients; (4) in THP-1 monocytes, activation of Toll-like receptors 2 and 4 increased mRNA levels of S100A8, S100A9, and S10012 and interleukin-1β, interferon γ, and releasate from thrombin-activated platelets significantly enhanced the expression of S100A12.

Conclusions—
Our findings support a link between calgranulins and atherogenesis and suggest that these mediators, and in particular S100A12, may be related to plaque instability.
Covert Neurological Symptoms Associated With Silent Infarcts From Midlife to Older Age
Authors: Windham Beverly G. , Griswold Michael E. , Shibata Dean , Penman Alan , Catellier Diane J. , Mosley Thomas H. 
Published: March 2012

Background and Purpose—
Unrecognized or unreported stroke-like symptoms, called covert symptoms, occur in persons free of clinical stroke. Whether covert symptoms are associated with subclinical brain infarcts (SBIs) is unknown. This study examined the association between covert stroke-like symptoms and SBI/stroke in persons with no history of stroke or transient ischemic attack.

Methods—
A total of 1881 Atherosclerosis Risk in Communities (ARIC) participants free of clinical stroke or transient ischemic attack (40% male, 50% black, 47–70 years) were queried for covert symptoms and underwent cerebral MRI during the baseline MRI visit. Symptoms were reassessed after 3 years at Visit 4 (n=1001; 39% male, 50% black) and approximately 10 years with a follow-up MRI (n=1006; 40% male, 50% black, 61–83 years).

Results—

Covert symptoms were associated with prevalent SBI (OR, 1.94; 95% CI, 1.21–3.11;
P
=0.006). No support was found for associations between baseline MRI symptoms and SBI at the follow up MRI visit. In participants without SBI at baseline, symptoms at Visit 4 (OR, 2.96; 1.23–7.13;
P
=0.016) and symptoms at the follow-up MRI visit (OR, 4.29; 2.51–7.33;
P
<0.001) were associated with a combined outcome of new SBI/clinical stroke on follow-up MRI. Covert symptoms at follow-up MRI visit were also associated with having new SBI (OR, 2.26; 1.18–4.32;
P
=0.014) on the follow-up MRI that were not seen on the baseline MRI.

Conclusions—
Covert neurological symptoms were associated with prevalent SBI, and when ascertained at the time of follow-up MRI, with new SBI. Covert symptoms may reflect heightened risk for infarcts.
Patient-Reported Auditory Functions After Stroke of the Central Auditory Pathway
Authors: Bamiou Doris-Eva , Werring David , Cox Karen , Stevens John , Musiek Frank E. , Brown Martin M. , Luxon Linda M. 
Published: March 2012

Background and Purpose—
Auditory functional limitations experienced by patients after stroke of the central auditory pathways remain underinvestigated.

Purpose—
To measure patient-reported hearing difficulties in everyday life in nonaphasic patients with stroke of the auditory brain versus normal control subjects. To examine how hearing difficulties correlate with auditory tests and site of lesion in individual cases.

Methods—
We recruited 21 individuals with auditory brain stroke (excluding those with aphasia) diagnosed on the basis of a brain MRI conducted 1 to 2 weeks after the stroke and assessed in the chronic stage of stroke. Twenty-three controls matched for age and hearing were also recruited. All subjects completed the Amsterdam Inventory for Auditory Disability (consisting of subscales of sound detection, recognition, localization, speech in quiet, speech in noise) and underwent baseline audiometry and central auditory processing tests (dichotic digits, frequency and duration patterns, gaps in noise).

Results—
Sound recognition and localization subscores of the inventory were significantly worse in case subjects versus control subjects, with severe and significant functional limitation (z score >3) reported by 9 out of 21 case subjects. None of the inventory subscales correlated with audiometric thresholds, but localization and recognition subscales showed a moderate to strong correlation with dichotic digits (left ear) and pattern tests.

Conclusions—
A substantial proportion of patients may experience and report severe auditory functional limitations not limited to speech sounds after stroke of the auditory brain. A hearing questionnaire may help identify patients who require more extensive assessment to inform rehabilitation plans.
Manual Aspiration Thrombectomy
Authors: Jankowitz Brian , Aghaebrahim Amin , Zirra Alexandra , Spataru Oana , Zaidi Syed , Jumaa Mouhammad , Ruiz-Ares Gerardo , Horowitz Michael , Jovin Tudor G. 
Published: March 2012

Background and Purpose—
We evaluated recanalization rates, clinical outcomes, and safety when manual aspiration thrombectomy is used in conjunction with other thrombolytic modalities in a consecutive case series of patients with large vessel intracranial occlusion.

Methods—
We conducted a retrospective review of a prospectively acquired acute endovascular stroke database. Manual aspiration thrombectomy was carried out with Distal Access and Penumbra reperfusion catheters of different sizes placed in the thrombus and aspirated with a syringe.

Results—
We identified 191 patients: Occlusion locations were as follows: M1% to 50%, M2% to 10%, internal carotid artery terminus 25%, and vertebrobasilar 15%. Median treatment duration was 90 minutes. Recanalization results were Thrombolysis in Myocardial Ischemia 2/3 93%, Thrombolysis in Myocardial Ischemia 3 27%, Thrombolysis In Cerebral Infarction 2a/2b/3 91%, Thrombolysis In Cerebral Infarction 2b/3 71%, and Thrombolysis In Cerebral Infarction 3 25%. Larger catheters were associated with higher recanalization rates. Parenchymal hematoma rate was 13.6%. The favorable outcome (90-day modified Rankin Scale ≤2) rate was 54%. Mortality at 90 days was 25%.

Conclusions—
Manual aspiration thrombectomy is a useful addition to the armamentarium of endovascular treatment modalities for acute stroke.