bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of the hypotensive action of methyldopa in normal and immunosympathectomized rats
Authors: AYITEY‐SMITH E. , VARMA D. R. 
Published: July 2012

Summary
The antihypertensive action of methyldopa was investigated in the light of the prevailing false sympathetic neurotransmitter hypothesis of Day & Rand (1963). Immunosympathectomized and normal animals were used for the investigation.
Methyldopa in a single injection significantly decreased the blood pressure in control hypertensive, immunosympathectomized normotensive, and normal rats. Guanethidine did not decrease the blood pressure of immunosympathectomized rats; it decreased the blood pressure of control and control hypertensive rats.
The hypotensive effect of methyldopa was not antagonized by adrenoceptor and ganglion blocking agents or by the inhibition of dopamine β‐oxidase.
High doses of methyldopa produced less hypotension than relatively low doses. This might be due to an antagonism of the hypotensive effect by methylnoradrenaline, which is formed from methyldopa.
The antihypertensive action of methyldopa could not be correlated with any change in aortic sodium or potassium.
It is concluded that methyldopa does not exert its hypotensive effect by producing a weakly active false sympathetic neurotransmitter.
Metabolism of prostaglandin E1 in dog kidneys
Authors: NAKANO J. 
Published: July 2012

Summary
The biotransformation of prostaglandin E1 (PGE1) was studied in the isolated, perfused dog kidneys.
An average 43% of PGE1 was converted into the less polar metabolite I by a single passage through the kidney. As the re‐circulation of the perfusate continued, PGE1 was converted not only into metabolite I but also the least polar metabolite II. The velocity of the conversion of PGE1 into metabolite I was significantly greater than that into metabolite II. Usually, six passages elapsed before maximum degradation of PGE1 occurred.
Further separation with silicic acid column chromatography and gas‐liquid chromatography showed that metabolite II consists of two individual metabolites, metabolite IIa and metabolite IIb.
The present study indicates that the kidney biotransforms PGE1 rather rapidly into three metabolites which are less polar than PGE1.
Subcellular localization of renin and kininogenase in the rat kidney
Authors: NUSTAD K. , RUBIN I. 
Published: July 2012

Summary
The distribution of enzymatic activities was determined in subcellular fractions of rat kidney cortex homogenates after various homogenization procedures. The specific activities of kininogenase (KGA), BAEE esterase (pH 8.5), alkaline phosphatase and glucose‐6‐phosphatase were, on average, 3.4 times higher in the microsomal fraction than in the whole homogenate. The total amount of these activities in the microsomal fraction after gentle, ordinary and forced homogenization were about 15, 40 and 65% of total recovered activities, respectively. These results confirmed the localization of KGA in the microsomal fraction.
Renin activity was primarily recovered in the heavy mitochondrial fraction. When the force of the homogenization was increased some renin activity was shifted to the soluble fraction.
When a mixture of renin and purified urinary KGA was given intravenously to an anaesthetized rat, a hypotensive response due to the KGA was followed by a hypertensive renin response. Over a certain range of concentrations KGA and renin could be measured simultaneously. In fractions of kidney homogenates, however, KGA activity was too low to be measured by this method.
The effect of benzodiazepines and atropine on exploratory behaviour and motor activity of mice
Authors: AHTEE LIISA , SHILLITO ELIZABETH 
Published: July 2012

Summary
Male albino mice were watched in red light on a tunnel board to test exploration and their motor activity was assessed in an open cage, 30 min after intraperitoneal injection of drugs.
Atropine and methylatropine 5 or 10 mg/kg did not alter the motor activity of the mice, while chlordiazepoxide 25 or 50 mg/kg and diazepam 10 or 20 mg/kg increased the activity, especially at the lower of the two doses used.
All the compounds used except methylatropine adversely affected the exploratory behaviour.
When atropine 10 mg/kg was given with the benzodiazepines, the activity of the mice was reduced and exploratory behaviour was further impaired. Methylatropine did not have this effect.
Suppressing inflammation by inhibiting the NF‐κB pathway contributes to the neuroprotective effect of angiotensin‐(1‐7) in rats with permanent cerebral ischaemia
Authors: Jiang Teng , Gao Li , Guo Jun , Lu Jie , Wang Yao , Zhang Yingdong 
Published: July 2012

BACKGROUND AND PURPOSE Angiotensin‐(1‐7) [Ang‐(1‐7)] has anti‐inflammatory effects in peripheral organs, but its effects in ischaemic stroke are unclear as yet. We investigated whether its anti‐inflammatory effect contributes to the neuroprotection induced by Ang‐(1‐7) in a rat model of permanent middle cerebral artery occlusion (pMCAO).EXPERIMENTAL APPROACH We infused Ang‐(1‐7), Mas receptor antagonist A‐779, angiotensin II type 2 receptor antagonist PD123319 or artificial CSF into the right lateral ventricle of male Sprague‐Dawley rats from 48 h before onset of pMCAO until the rats were killed. Twenty‐four hours after pMCAO, the neuroprotective effect of Ang‐(1‐7) was analysed by evaluating infarct volume and neurological deficits. The levels of oxidative stress were detected by spectrophotometric assay. The activation of NF‐κB was assessed by Western blot and immunohistochemistry analysis. The level of COX‐2 was tested by Western blot analysis and concentrations of pro‐inflammatory cytokines were measured by elisa.KEY RESULTS Infusion of Ang‐(1‐7), i.c.v., significantly reduced infarct volume and improved neurological deficits. It decreased the levels of oxidative stress and suppressed NF‐κB activity, which was accompanied by a reduction of pro‐inflammatory cytokines and COX‐2 in the peri‐infarct regions. These effects of Ang‐(1‐7) were reversed by A‐779 but not by PD123319. Additionally, infusion of A‐779 alone increased oxidative stress levels and enhanced NF‐κB activity, which was accompanied by an up‐regulation of pro‐inflammatory cytokines and COX‐2.CONCLUSION AND IMPLICATIONS Our findings indicate that suppressing NF‐κB dependent pathway via Mas receptor may represent one mechanism that contributes to the anti‐inflammatory effects of Ang‐(1‐7) in rats with pMCAO.
Rosuvastatin prevents angiotensin II‐induced vascular changes by inhibition of NAD(P)H oxidase and COX‐1
Authors: Colucci Rocchina , Fornai Matteo , Duranti Emiliano , Antonioli Luca , Rugani Ilaria , Aydinoglu Fatma , Ippolito Chiara , Segnani Cristina , Bernardini Nunzia , Taddei Stefano , Blandizzi Corrado , Virdis Agostino 
Published: July 2012

Background and PurposeNAD(P)H oxidase and COX‐1 participate in vascular damage induced by angiotensin II. We investigated the effect of rosuvastatin on endothelial dysfunction, vascular remodelling, changes in extracellular matrix components and mechanical properties of small mesenteric arteries from angiotensin II‐infused rats.Experimental ApproachMale rats received angiotensin II (120 ng·kg−1·min−1, subcutaneously) for 14 days with or without rosuvastatin (10 mg·kg−1·day−1, oral gavage) or vehicle. Vascular functions and morphological parameters were assessed by pressurized myography.Key ResultsIn angiotensin II‐infused rats, ACh‐induced relaxation was attenuated compared with controls, less sensitive to L‐NAME, enhanced by SC‐560 (COX‐1 inhibitor) or SQ‐29548 (prostanoid TP receptor antagonist), and normalized by the antioxidant ascorbic acid or NAD(P)H oxidase inhibitors. After rosuvastatin, relaxations to ACh were normalized, fully sensitive to L‐NAME, and no longer affected by SC‐560, SQ‐29548 or NAD(P)H oxidase inhibitors. Angiotensin II enhanced intravascular superoxide generation, eutrophic remodelling, collagen and fibronectin depositions, and decreased elastin content, resulting in increased vessel stiffness. All these changes were prevented by rosuvastatin. Angiotensin II increased phosphorylation of NAD(P)H oxidase subunit p47phox and its binding to subunit p67phox, effects inhibited by rosuvastatin. Rosuvastatin down‐regulated vascular Nox4/NAD(P)H isoform and COX‐1 expression, attenuated the vascular release of 6‐keto‐PGF1α, and enhanced copper/zinc‐superoxide dismutase expression.Conclusion and ImplicationsRosuvastatin prevents angiotensin II‐induced alterations in resistance arteries in terms of function, structure, mechanics and composition. These effects depend on restoration of NO availability, prevention of NAD(P)H oxidase‐derived oxidant excess, reversal of COX‐1 induction and its prostanoid production, and stimulation of endogenous vascular antioxidant defences.
First and second generation antipsychotics influence hippocampal gamma oscillations by interactions with 5‐HT3 and D3 receptors
Authors: Schulz Steffen B , Heidmann Karin E , Mike Arpad , Klaft Zin‐Juan , Heinemann Uwe , Gerevich Zoltan 
Published: July 2012

BACKGROUND AND PURPOSE Disturbed cortical gamma band oscillations (30–80 Hz) have been observed in schizophrenia: positive symptoms of the disease correlate with an increase in gamma oscillation power, whereas negative symptoms are associated with a decrease.EXPERIMENTAL APPROACH Here we investigated the effects of first and second generation antipsychotics (FGAs and SGAs, respectively) on gamma oscillations. The FGAs haloperidol, flupenthixol, chlorpromazine, chlorprothixene and the SGAs clozapine, risperidone, ziprasidone, amisulpride were applied on gamma oscillations induced by acetylcholine and physostigmine in the CA3 region of rat hippocampal slices.KEY RESULTS Antipsychotics inhibited the power of gamma oscillations and increased the bandwidth of the gamma band. Haloperidol and clozapine had the highest inhibitory effects. To determine which receptor is responsible for the alterations in gamma oscillations, the effects of the antipsychotics were plotted against their pKi values for 19 receptors and analysed for correlation. Our results indicated that 5‐HT3 receptors have an enhancing effect on gamma oscillations whereas dopamine D3 receptors inhibit them. To test this prediction, m‐chlorophenylbiguanide, PD 128907 and CP 809101, selective agonists at 5‐HT3, D3 and 5‐HT2C receptors were applied and revealed that 5‐HT3 receptors indeed enhanced the gamma power whereas D3 receptors reduced it. As predicted, 5‐HT2C receptors had no effects on gamma oscillations.CONCLUSION AND IMPLICATIONS Our data suggest that antipsychotics alter hippocampal gamma oscillations by interacting with 5‐HT3 and dopamine D3 receptors. Moreover, a correlation of receptor affinities with the biological effects can be used to predict targets for the pharmacological effects of multi‐target drugs.
Invariant NKT cells increase drug‐induced osteosarcoma cell death
Authors: Fallarini S , Paoletti T , Orsi Battaglini N , Lombardi G 
Published: July 2012

BACKGROUND AND PURPOSE In osteosarcoma (OS) patients, only a limited number of drugs are active and the regimens currently in use include a combination of at least two of these drugs: doxorubicin, cisplatin, methotrexate and ifosfamide. Today, 30–40% of patients still die of OS highlighting the urgent need for new treatments. Invariant NKT (iNKT) cells are a lymphocyte lineage with features of both T and NK cells, playing important roles in tumour suppression. Our aim was to test whether the cytoxicity induced by cisplatin, doxorubicin and methotrexate against OS cells can be enhanced by iNKT cell treatment.EXPERIMENTAL APPROACH iNKT cells were purified from human peripheral blood mononuclear cells by cell sorting (Vα24Vβ11+ cells) and used as effector cells against OS cells (U2‐OS, HOS, MG‐63). Cell death (calcein‐AM method), perforin/granzyme B and Fas/FasL expressions were determined by flow cytometry. CD1d expression was analysed at both the gene and protein level.KEY RESULTS iNKT cells were cytotoxic against OS cells through a CD1d‐dependent mechanism. This activity was specific for tumour cells, because human CD1d+ mesenchymal stem cells and CD1d‐ osteoblasts were not affected. iNKT cell treatment enhanced drug‐induced OS cell death in a concentration‐dependent manner and this effect was reduced in CD1d‐silenced OS cells.CONCLUSION AND IMPLICATIONS iNKT cells kill malignant, but not non‐malignant, cells. iNKT cell treatment enhances the cytotoxicity of anti‐neoplastic drugs against OS cells in a CD1d‐dependent manner. The present data encourage further studies on the use of iNKT cells in OS therapy.
Prenatal Alcohol Exposure, Attention‐Deficit/Hyperactivity Disorder, and Sluggish Cognitive Tempo
Authors: Graham Diana M. , Crocker Nicole , Deweese Benjamin N. , Roesch Scott C. , Coles Claire D. , Kable Julie A. , May Philip A. , Kalberg Wendy O. , Sowell Elizabeth R. , Jones Kenneth L. , Riley Edward P. , Mattson Sarah N. ,   the CIFASD
Published: July 2012

BackgroundChildren with heavy prenatal alcohol exposure often meet criteria for attention‐deficit/hyperactivity disorder (ADHD). ADHD research has examined subtype differences in symptomatology, including sluggish cognitive tempo (SCT). This construct is defined by behavioral symptoms including hypoactivity and daydreaming and has been linked to increased internalizing behaviors. The current study examined whether similar findings are displayed in children with prenatal alcohol exposure.MethodsAs part of a multisite study, caregivers of 272 children (8 to 16 years) completed the SCT Scale and Child Behavior Checklist (CBCL). Four groups were included: alcohol‐exposed children with ADHD (ALC+; n = 75), alcohol‐exposed children without ADHD (ALC−; n = 35), nonexposed children with ADHD (ADHD; n = 60), and nonexposed children without ADHD (CON; n = 102). SCT and CBCL scores were analyzed using 2 (exposure) × 2 (ADHD) analyses of variance. Pearson's correlations measured the relationships between SCT, CBCL, and Full Scale IQ (FSIQ). Discriminant function analysis examined whether SCT items could accurately classify groups.ResultsAnalyses revealed significant main effects of exposure and ADHD on SCT and internalizing and externalizing scores and significant interaction effects on SCT and internalizing scores. SCT significantly correlated with internalizing, externalizing, and attention ratings in all groups and with FSIQ in ALC+. Discriminant function analysis indicated that specific SCT items could distinguish ALC− from CON.ConclusionsAlcohol‐exposed children exhibited elevated SCT scores. Elevations were related to increased parent ratings of internalizing and externalizing behaviors and attention. These findings are observed in alcohol‐exposed children regardless of ADHD symptoms and specific SCT items proved useful in distinguishing exposed children, suggesting clinical utility for this measure in further defining the neurobehavioral profile related to prenatal alcohol exposure.
Evaluation of Submucosally Injected Polyethylene Glycol‐Based Hydrogel and Bovine Cross‐Linked Collagen in the Canine Urethra using Cystoscopy, Magnetic Resonance Imaging and Histopathology
Authors: Sumner Julia P. , Hardie Robert J. , Henningson Jamie N. , Drees Randi , Markel Mark D. , Bjorling Dale 
Published: July 2012

ObjectiveTo (1) investigate the tissue response to a novel urethral bulking agent, polyethylene glycol carboxymethyl cellulose hydrogel (PEG‐CMC) injected submucosally in the canine urethra and (2) compare PEG‐CMC with bovine collagen (BC), the current standard for urethral bulking.Study designExperimental study.AnimalsPurpose‐bred female hound dogs (n = 8).MethodsStandardized submucosal urethral injections of BC and PEG‐CMC were performed in 8 female dogs. Injection sites were evaluated by cystoscopy on days 0 (n = 8), 30 (n = 4), and 90 (n = 4), magnetic resonance imaging on days 0 (n = 8), 30 (n = 8), and 90 (n = 4) and by histopathology on days 30 (n = 4) and 90 (n = 4).ResultsBoth PEG‐CMC and BC were detectable on MRI as hyperintense foci on T2‐weighted images. Grossly, PEG‐CMC formed more prominent blebs than BC. On follow‐up cystoscopic examination, 6/8 PEG‐CMC injection needle tracts were visible, and 3 of these sites had mucosal erosions. Histopathologic scores for foreign body reaction and inflammation were significantly higher for PEG‐CMC compared with BC (P < 0.005). BC elicited a lymphoplasmacytic reaction whereas PEG‐CMC incited a granulomatous response.ConclusionsThe overall physical characteristics and histologic response associated with PEG‐CMC support its use as a urethral bulking agent; however, the current formulation needs to be adjusted for clinical use.
A Multicity Neighborhood Analysis of Foreclosure and Crime
Authors: Baumer Eric P. , Wolff Kevin T. , Arnio Ashley N. 
Published: July 2012

ObjectiveWe examine whether there is a significant effect of foreclosure on robbery and burglary across neighborhoods, and whether this varies systematically across cities. Specifically, we consider whether several city‐level attributes—overall foreclosure rates, levels of socioeconomic disadvantage and prior vacancy rates, the degree of recent new housing construction, housing affordability, and the quantity and quality of policing—moderate the relationship between neighborhood levels of foreclosure and crime.MethodsWe examine our research questions with a rich database on foreclosure, crime, and other attributes for 5,517 census tracts situated within 50 large U.S. cities. We estimate multilevel overdispersed Poisson regression to explore city‐level variability in the neighborhood‐level effects of foreclosure on crime.ResultsWe find significant between‐city variation in the estimated effects of neighborhood‐level rates of foreclosure on crime. High neighborhood foreclosure rates yield elevated robbery rates primarily in cities with relatively low foreclosure rates and high levels of socioeconomic disadvantage. Foreclosure is more strongly related to burglary rates in cities with little new home construction and declining police forces.ConclusionsThe broader city‐level context in which neighborhoods are located is important for shaping whether high rates of foreclosure yield elevated crime rates.
Foreclosure Depresses Voter Turnout: Neighborhood Disruption and the 2008 Presidential Election in California
Authors: Estrada‐Correa Vanesa , Johnson Martin 
Published: July 2012

ObjectiveWe investigate whether voters in communities with high rates of foreclosure will find it more difficult to participate in elections, given social disruptions associated with home loss in their neighborhoods.MethodsWe estimate the community‐level effects of foreclosure on turnout rates in California ZIP Codes during the 2008 presidential election and an individual‐level turnout model using housing data merged with California voter data.ResultsForeclosure rates are associated with reduced participation independent of local economic conditions, rates of education, ethnic composition, or individual partisanship, age, and habitual participation.ConclusionGiven the relationship between the foreclosure crisis and political participation, this research suggests the need for further investigation. We are especially interested in the potential that housing foreclosure further exacerbates ethnic and economic inequality due to the preponderance of subprime loans, distressed mortgages, and foreclosures in communities of color and lower socioeconomic status.
Hippocampal Magnetization Transfer Ratio at 3T: Validation of Automated Postprocessing and Comparison of Quantification Metrics
Authors: Sidharthan Shawn , Hutten Ryan , Glielmi Christopher , Du Hongyan , Malone Fiona , Ragin Ann B. , Edelman Robert R. , Wu Ying 
Published: July 2012

ABSTRACTBACKGROUNDTo investigate the reliability of a novel magnetization transfer ratio (MTR) postprocessing technique for the hippocampus using histogram analysis, and compare results to more established volumetric measurements. This study is conducted in healthy volunteers as a precursor to future applications regarding progressive neurologic diseases, such as Alzheimer's disease.METHODSEight healthy subjects were scanned twice with interval of 1 week using quantitative magnetic resonance imaging (MRI). Automated pixel‐wise analysis was performed for the hippocampal regions of each patient. Reliability was assessed using intraclass correlation coefficients (ICCs), coefficients of variation (COVs), and instrumental standard deviation (ISD).RESULTSReliable metrics were 25th percentile, median, 75th percentile, peak location, and mean approach (ranges: ICC = .93‐.96, COV = 2.71‐3.88%, ISD .78‐1.01). Histogram peak height had ICC below .7, and a COV above 10%. Volumetric measurements had (ICC = .95‐.97, COV = 1.43‐3.39%).CONCLUSIONExcellent scan‐rescan reproducibility (ICC > .9, COV < 10%) was observed for specific MTR histogram metrics and the mean MTR approach. These results are comparable to the volumetric approach. Future studies can examine the possibility that MTR changes precede morphological changes as this study suggests that both MTR and volumetric measurements of the hippocampus can be used as reliable imaging tools.
Prevalence of Symptomatic Intracranial Atherosclerosis in Caucasians: A Prospective, Multicenter, Transcranial Doppler Study
Authors: Tsivgoulis Georgios , Vadikolias Konstantinos , Heliopoulos Ioannis , Katsibari Chaido , Voumvourakis Konstantinos , Tsakaldimi Soultana , Boutati Eleni , Vasdekis Spyros N. , Athanasiadis Dimitrios , Al‐Attas Omar S. , Charalampidis Paris , Stamboulis Elefterios , Piperidou Charitomeni 
Published: July 2012

ABSTRACTBACKGROUNDThere are limited data available regarding symptomatic intracranial atherosclerosis (SIA) prevalence in Caucasians. We sought to investigate SIA prevalence among Caucasian patients hospitalized with acute cerebral ischemia (ACI) in a prospective, multicenter Transcranial Doppler sonography (TCD) study.METHODSConsecutive patients with ACI were prospectively evaluated with TCD over a 24‐month‐period. The previously validated criteria of SONIA trial were used for detection of >50% intracranial stenosis with TCD. Brain angiography was performed to confirm the diagnosis in cases with abnormal TCD findings. SIA was diagnosed when there was evidence of a cerebral infarction in the territory of the stenotic artery (identified by TCD and confirmed by Magnetic resonance angiography [MRA]/Computed tomography angiography [CTA]).RESULTSA total of 467 consecutive patients with ACI (60.4% men, mean age 58 ± 14 years) were evaluated. SIA was documented in 43 patients (9.2%; 95%CI: 6.9%‐12.2%). The most common SIA location was M1MCA (34.9%) followed by TICA (18.8%). Diabetes mellitus (OR: 4.25, 95%CI: 2.18‐8.26; P < .001) and hypertension (OR: 2.41, 95%CI: 1.02‐5.67; P = .045) were independently associated with SIA on multivariate models adjusting for potential confounders.CONCLUSIONSSIA was identified in almost 10% of patients admitted with symptoms of ACI. These preliminary findings support further collaborative initiatives among stroke physicians to increase the yield of SIA detection in Caucasian patients with ACI.