bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pelvic free fluid: clinical importance for reproductive age women with blunt abdominal trauma
Authors: Ormsby E. L. , Geng J. , McGahan J. P. , Richards J. R. 
Published: August 2005

AbstractObjectiveTo evaluate the importance of isolated pelvic free fluid (FF) detected by ultrasound examination in pregnant patients and in non‐pregnant reproductive age women with blunt abdominal trauma (BAT).MethodsReproductive age women aged 10–50 years who presented with BAT and underwent focused abdominal sonography for trauma (FAST) from January 1995 to June 2002 at a Level 1 trauma center were included. Patients were assigned to four groups according to the location of FF detected by ultrasound (Group 1, no FF; Group 2, FF in pelvis; Group 3, FF in abdomen; Group 4, FF in abdomen and pelvis). Ultrasound findings were compared with intra‐abdominal and pelvic injuries detected by computed tomography and/or laparotomy. Pair‐wise comparison was performed using a Fisher's exact test.ResultsUltrasound detection of FF in the abdomen alone or FF in the abdomen and pelvis was significantly associated with intra‐abdominal injury (IAI) compared to those without FF (P < 0.001) for both pregnant and non‐pregnant reproductive age women. FF isolated to the pelvis was also associated with a higher injury rate compared to no FF in pregnant women (30% vs. 3%, P = 0.005) and in non‐pregnant reproductive age women (39.5% vs. 3.7%, P < 0.001).ConclusionsIn reproductive age women with BAT, ultrasound detection of FF in the abdomen alone, in both the abdomen and pelvis, or isolated to the pelvis is associated with a higher IAI rate. Therefore, isolated FF in the pelvis should not necessarily be considered physiological in pregnant and non‐pregnant patients with BAT. Copyright © 2005 ISUOG. Published by John Wiley & Sons, Ltd.
Sildenafil prevents indomethacin‐induced gastropathy in rats: role of leukocyte adherence and gastric blood flow
Authors: Santos Camila L , Souza Marcellus H L P , Gomes Antoniella S , Lemos Henrique P , Santos Armênio A , Cunha Fernando Q , Wallace John L 
Published: August 2005

Nitric oxide (NO) is an important mediator of gastric mucosal defense. Sildenafil (SILD), a cyclic GMP‐specific phosphodiesterase inhibitor, promotes an increase in cGMP concentrations in the gastrointestinal tract. cGMP mediates many of the biological actions of NO.
We tested the hypothesis that SILD could increase mucosal defense against indomethacin‐induced gastropathy in rats.
SILD (1, 4 or 10 mg kg−1, p.o.) pretreatment significantly reduced (P<0.01) the gastric damage and the increase in gastric myeloperoxidase (MPO) activity elicited by indomethacin (20 mg kg−1 p.o.), with the maximal effect at the dose of 10 mg kg−1.
L‐NAME (3, 10 or 20 mg kg−1, i.p.) dose dependently reversed the protective effects of SILD, an effect not seen when L‐arginine (L‐ARG) (200 mg kg−1, i.p.) was co‐administered with L‐NAME.
Indomethacin‐induced leukocyte adhesion, assessed by intravital microscopy, was decreased (P<0.01) by SILD, and this effect was reversed by L‐NAME cotreatment.
Indomethacin elicited a decrease in gastric blood flow and in gastric PGE2 levels. SILD was able to prevent the decrease in gastric blood flow (P<0.01), without diminishing the inhibitory effect of indomethacin on prostaglandin synthesis.
These results indicate that SILD, acting via NO‐dependent mechanisms, prevents indomethacin‐induced gastropathy, possibly through a reduction of leukocyte adhesion and maintenance of gastric blood flow.

British Journal of Pharmacology (2005) 146, 481–486. doi:10.1038/sj.bjp.0706361
Direct demonstration of β1‐ and evidence against β2‐ and β3‐adrenoceptors, in smooth muscle cells of rat small mesenteric arteries
Authors: Briones Ana M , Daly Craig J , Jimenez‐Altayo Francesc , Martinez‐Revelles Sonia , Gonzalez Jose M , McGrath John C , Vila Elisabet 
Published: August 2005

Recent evidence supports additional subtypes of vasodilator β‐adrenoceptor (β‐AR) besides the ‘classical’ β2. The aim of this study was to investigate the distribution of β‐ARs in the wall of rat mesenteric resistance artery (MRA), to establish the relative roles of β‐ARs in smooth muscle and other cell types in mediating vasodilatation and to analyse this in relation to the functional pharmacology.
We first examined the vasodilator β‐AR subtype using ‘subtype‐selective’ agonists against the, commonly employed, phenylephrine‐induced tone. Concentration‐related relaxation was produced by isoprenaline (pEC50: 7.70±0.1) (β1 and β2). Salbutamol (β2), BRL 37344 (β3) and CGP 12177 (atypical β) caused relaxation but were 144, 100 and 263 times less potent than isoprenaline; the ‘β3‐adrenoceptor agonist’ CL 316243 was ineffective.
In arteries precontracted with 5‐HT or U 46619, isoprenaline produced concentration‐related relaxation but salbutamol, BRL 37344, CGP 12177 and CL 316243 did not. SR 59230A, CGP 12177 and BRL 37344 caused a parallel rightward shift in the concentration–response curve to phenylephrine indicating competitive α1‐AR antagonism, explaining the false‐positive ‘vasodilator’ action against phenylephrine‐induced tone. Endothelial denudation but not L‐NAME slightly attenuated isoprenaline‐mediated vasodilatation in phenylephrine and U 46619 precontracted MRA.
The β‐AR fluorescent ligand BODIPY TMR‐CGP 12177 behaved as an irreversible β1‐AR antagonist in MRA and bound to the surface and inside vascular smooth muscle cells in intact vascular wall. β‐ARs in smooth muscle cells were observed in a perinuclear location, consistent with the location of Golgi and endoplasmic reticulum.
Binding of BODIPY TMR‐CGP 12177 was inhibited by BAAM (1 μM) in all three vascular tunics, confirming the presence of β‐ARs in adventitia, media and intima. Binding in adventitia was observed in both neuronal and non‐neuronal cell types. Lack of co‐localisation with a fluorescent ligand for α‐ARs confirms the selectivity of BODIPY TMR‐CGP 12177 for β‐ARs over α‐ARs.
Our results support the presence of functional vasodilator β1‐ARs and show that they are mainly located in smooth muscle cells. Furthermore, we have demonstrated, for the first time, the usefulness of BODIPY TMR‐CGP 12177 for identifying β‐AR distribution in the ‘living’ vascular wall.

British Journal of Pharmacology (2005) 146, 679–691. doi:10.1038/sj.bjp.0706369
Pharmacokinetic/pharmacodynamic modelling of NSAIDs in a model of reversible inflammation in the cat
Authors: Giraudel Jerome M , Diquelou Armelle , Laroute Valerie , Lees Peter , Toutain Pierre‐Louis 
Published: August 2005

Data on the relationships between plasma concentration and analgesic and anti‐inflammatory effects of NSAIDs are limited because most inflammation models do not permit pharmacokinetic/pharmacodynamic (PK/PD) modelling to be readily performed.
In this study, a kaolin‐induced inflammation model in the cat was evaluated for pre‐clinical characterization of the pharmacodynamic profiles of NSAIDs (determination of efficacy, potency, sensitivity (that is the slope of the concentration–effect relationship) and duration of drug response), using meloxicam as a probe article.
Indirect response PK/PD models described the time course and magnitude of responses produced by 0.3 mg kg−1 meloxicam administered subcutaneously. For endpoints for which spontaneous recovery from inflammation was superimposed on drug response, a PK/PD model with a time‐dependent Kin was used to allow for the spontaneous changes of the inflammation with time.
The selected endpoints were suitable for studying simultaneously the analgesic, anti‐inflammatory and antipyretic effects of meloxicam, allowing comparison of relative potencies for these effects. Mean±s.d. IC50 or EC50 values (ng ml−1) were 777±124 (body temperature), 841±187 (locomotion variable), 883±215 (pain score), 911±189 (lameness score) and 1298±449 (skin temperature difference). Corresponding mean times±s.d. of peak responses (h) were 5.6±1.3, 8.6±3.8, 5.2±5.0, 5.6±3.7 and 4.3±2.4, respectively.
As the pharmacokinetic profiles of meloxicam in cats and humans are similar, simulations of several dosage regimens in the cat provided a pre‐clinical basis, illustrating the value of the cat model for predicting a clinical dose regimen for evaluation in man. The predicted loading doses (mg kg−1) of meloxicam in the cat producing 70% of the maximum attainable responses were 0.29 (body temperature), 0.32 (lameness score), 0.33 (overall locomotion variable), 0.36 (pain score) and 0.50 (skin temperature difference). The values are similar to or somewhat greater than the clinically recommended doses both in cats (0.3 mg kg−1) and humans (7.5–15 mg, that is, between 0.1 and 0.3 mg kg−1).
These findings indicate the potential value of the cat as a laboratory model, and of a PK/PD modelling approach in assisting NSAID development programs in animals and humans.

British Journal of Pharmacology (2005) 146, 642–653. doi:10.1038/sj.bjp.0706372
Sustained aquaretic effect of the V2‐AVP receptor antagonist, RWJ‐351647, in cirrhotic rats with ascites and water retention
Authors: Ros Josefa , Fernández‐Varo Guillermo , Muñoz‐Luque Javier , Arroyo Vicente , Rodés Juan , Gunnet Joseph W , Demarest Keith T , Jiménez Wladimiro 
Published: August 2005

A disturbance in body water homeostasis is a common feature in advanced cirrhosis. This disturbance is always associated with the existence of ascites and is characterized by an inability to adjust the amount of water excreted in the urine to the amount of water ingested. Vasopressin (AVP) is of major importance in the pathogenesis of water retention and hyponatremia in cirrhosis.
The current study assessed the renal, hormonal and hemodynamic effects induced by 10‐day chronic oral administration of RWJ‐351647 (0.5 mg kg−1 daily), a new nonpeptide V2‐AVP antagonist, in rats with CCl4‐induced cirrhosis, ascites and severe water retention. Urine volume (UV), urine osmolality and sodium and potassium excretion were measured daily. At the end of the study, systemic hemodynamic parameters were also assessed.
Long‐term administration of RWJ‐351647 has an aquaretic effect in rats with cirrhosis, ascites, water retention and hypo‐osmolality. It increases UV (ANOVA: F=7.32, P<0.0001) and reduces urine osmolality (ANOVA: F=12.69, P<0.0001) throughout the entire period of treatment, thereby leading to a greater renal ability to excrete a water load at the end of the 10‐day treatment period (the percentage of water load excreted improved from 30±8 to 92±21%, P<0.025).
The nonpeptide AVP V2‐receptor antagonist RWJ‐351647 also increased sodium excretion without affecting creatinine clearance and blood pressure.
These data suggest that RWJ‐351647 could be therapeutically useful in the treatment of water retention in human cirrhosis.

British Journal of Pharmacology (2005) 146, 654–661. doi:10.1038/sj.bjp.0706375
Multifocal Acquired Sensory and Motor Neuropathy
Authors: Magda Paul , Latov Norman , Brannagan Thomas H , Goldfarb Adina , Chin Russell L , Sander Howard W 
Published: August 2005

Abstract

The electrodiagnostic studies of 13 consecutive patients with multifocal sensory and motor neuropathy of unknown etiology were reviewed to determine whether they exhibit features of demyelination or axonal degeneration. The type and frequency of demyelinating features, fulfillment of electrodiagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP), and response to immunotherapy were noted. Of 13 patients, 11 had at least one electrodiagnostic feature of demyelination at presentation and 2 had none. Seventeen percent to 77% of the patients fulfilled at least one of the published electrodiagnostic CIDP criteria, depending on the criteria used, but the number of demyelinating features per patient was less than reported for unselected patients with CIDP. Patients with multifocal sensory and motor neuropathy had a similar percentage of nerves with partial conduction block or F-wave prolongation as reported for unselected CIDP, but a smaller percentage of nerves exhibiting prolonged distal compound muscle action potential duration, distal latency prolongation or slowed conduction velocities. All treated patients, including 2 who did not meet any CIDP criteria, had at least a moderate response to immunotherapy. The results indicate that a large majority of, but not all, patients with idiopathic multifocal sensory and motor neuropathies exhibit electrodiagnostic features of demyelination, although fewer than seen in classic CIDP.
Polyneuropathy in Osteosclerotic Myeloma Coexisting With Hyaline Vascular Castleman's Disease
Authors: Sahota Preeti , Das Chandi P , Prabhakar Sudesh , Rajwanshi A , Singh Paramjeet , Khurana Dheeraj 
Published: August 2005

Abstract

Peripheral neuropathy is usually the presenting feature of POEMS syndrome. Approximately 50% of patients with POEMS syndrome are associated with osteosclerotic myeloma, a rare variant of multiple myeloma, and some with Castleman's disease, an unusual lymphoproliferative disorder. The multicentric plasma cell variant of Castleman's disease is usually associated with systemic disorders rather than its localized form of mediastinal lymphoid hyperplasia characterized by hyalinization of follicles and interfollicular vascular proliferation. We report a 48-year-old woman who presented with progressive sensorimotor demyelinating polyradiculoneuropathy, bilateral optic disc edema, hepatosplenomegaly, generalized lymphadenopathy, and skin changes. There was associated thrombocytosis, hypothyroidism, hypoparathyroidism, mixed osteolytic and osteosclerotic bone lesions, monoclonal gammopathy of IgG lambda type, and hyaline vascular type of Castleman's disease. This combination of POEMS syndrome, osteosclerotic myeloma with a hyaline vascular type of Castleman's disease is uncommon.
Percutaneous Conchotome Biopsy of the Deltoid and Quadricep Muscles in the Diagnosis of Neuromuscular Disorders
Authors: Poulsen Mette Buch , Bojsen-Moller Marie , Jakobsen Johannes , Andersen Henning 
Published: August 2005

Abstract

Clinical usefulness and safety of percutaneous conchotome biopsy of the deltoid muscle and of the quadriceps muscle was compared in patients suspected to have a neuromuscular disorder. In 121 samples from the quadriceps muscle and in 39 samples from the deltoid muscle, the quantity of muscle fibers was equal and the fraction of biopsies resulting in a specific diagnosis was similar (50% and 56%, respectively). Also, biopsy from the 2 locations resulted in the same distribution of neurogenic, inflammatory, and myopathic disorders. After quadriceps muscle biopsy, 2 patients developed vasovagal syncopes and one patient a local hematoma, whereas no complications occurred in the patients subjected to deltoid muscle biopsy. We conclude that biopsy from the deltoid muscle is clinically as useful and safe as biopsy from the quadriceps muscle.
Dendritic Cell Adhesion Is Enhanced on Endothelial Cells Preexposed to Calcineurin Inhibitors
Authors: Schlichting Christoph L , Schareck Wolfgang D , Weis Michael 
Published: August 2005

Abstract:

Chronic rejection remains a major complication in solid organ transplantation. Host alloreactive T cells (TC) can be activated by donor dendritic cells (DCs; direct allorecognition) or by recipient DCs (indirect allorecognition). A fundamental aspect of DC function is vascular invasion to present donor antigens to recipient naive TC in secondary lymphoid organs. We investigated the impact of calcineurin inhibitors on DC binding and transmigration to allogeneic human microvascular endothelial cells (ECs) with and without blocking of specific adhesion molecules. Recipient immature DCs were generated by culturing CD14+ human peripheral blood monocytes with GM-CSF and IL-4. DC adhesion and transmigration were investigated on allogeneic ECs preincubated with increasing concentrations of cyclosporine and tacrolimus. Experiments were repeated in the presence of blocking antibodies against LFA-1, PECAM-1, VCAM-1, and ICAM-1. Endothelial stimulation with cyclosporine A (100 and 300 ng/mL) and tacrolimus (15 ng/mL) significantly enhanced DC-EC adhesion and transmigration (P < 0.01). LFA-1 blockade on DCs significantly reduced cyclosporine- and tacrolimus-induced DC adhesion (P < 0.001). VCAM-1 blockade on ECs partially reversed cyclosporine-induced DC adhesion (P < 0.001), whereas DC adhesion under tacrolimus exposure was significantly decreased by ICAM-1 (P < 0.01) and PECAM-1 (P < 0.001) blockade. DC binding and transmigration on allogeneic ECs exposed to calcineurin inhibitors is concentration-dependently increased. Different adhesion molecule patterns on ECs are responsible for enhanced DC invasion under cyclosporine and tacrolimus exposure. We speculate that long-term immunosuppression mediates enhanced invasion of recipient DCs to the donor organ and therefore may aggravate chronic rejection.
Improved Mitochondrial Bioenergetics by Anesthetic Preconditioning During and After 2 Hours of 27°C Ischemia in Isolated Hearts
Authors: An Jianzhong , Camara Amadou K. S , Riess Matthias L , Rhodes Samhita S , Varadarajan Srinivasan G , Stowe David F 
Published: August 2005

Abstract:

We examined if sevoflurane given before cold ischemia of intact hearts (anesthetic preconditioning, APC) affords additional protection by further improving mitochondrial energy balance and if this is abolished by a mitochondrial KATP blocker. NADH and FAD fluorescence was measured within the left ventricular wall of 5 groups of isolated guinea pig hearts: (1) hypothermia alone; (2) hypothermia + ischemia; (3) APC (4.1% sevoflurane) + cold ischemia; (4) 5-HD + cold ischemia, and (5) APC + 5-HD + cold ischemia. Hearts were exposed to sevoflurane for 15 minutes followed by 15 minutes of washout at 37°C before cooling, 2 hours of 27°C ischemia, and 2 hours of 37°C reperfusion. The KATP channel inhibitor 5-HD was perfused before and after sevoflurane. Ischemia caused a rapid increase in NADH and a decrease in FAD that waned over 2 hours. Warm reperfusion led to a decrease in NADH and an increase in FAD. APC attenuated the changes in NADH and FAD and further improved postischemic function and reduced infarct size. 5-HD blocked the cardioprotective effects of APC but not APC-induced alterations of NADH and FAD. Thus, APC improves redox balance and has additive cardioprotective effects with mild hypothermic ischemia. 5-HD blocks APC-induced cardioprotective effects but not improvements in mitochondrial bioenergetics. This suggests that mediation of protection by KATP channel opening during cold ischemia and reperfusion is downstream from the APC-induced improvement in redox state or that these changes in redox state are not attenuated by KATP channel antagonism.
Vasorelaxant and Antioxidant Activity of Flavonols and Flavones: Structure-Activity Relationships
Authors: Woodman Owen L , Meeker William F , Boujaoude Mirna 
Published: August 2005

Abstract:

We investigated the structure-activity relationships regarding vascular and antioxidant activity of a range of synthetic flavonols and flavones with 3 or fewer hydroxyl (OH) or methoxyl substitutions. The relaxant responses and ability of the flavones/flavonols to inhibit phenylephrine (PE)- and Ca2+-induced contraction was determined in rat isolated thoracic aorta. The ability of these compounds to reduce the level of superoxide and preserve endothelium-dependent relaxation in the presence of oxidative stress was also examined. Four compounds impaired contraction to PE or Ca2+, in the potency order 3′-hydroxyflavonol > 3′,4′-dihydroxyflavonol > 7,4′-dihydroxyflavonol > 3′,4′-dihydroxyflavone. Flavonol, 3′,4′-dimethoxyflavonol, and flavone were significantly less active. The flavonoids caused concentration-dependent reductions in superoxide produced by rat aorta in the presence of NADPH. The most active compounds, 3′,4′-dihydroxyflavonol and 7,4′-dihydroxyflavonol, preserved endothelium-dependent relaxation in the presence of oxidative stress caused by pyrogallol or xanthine/xanthine oxidase. The results indicate that the catechol group is not critical for vascular relaxant or antioxidant activity, but rather, the important determinants for higher vascular and antioxidant activity of these compounds are the presence of a C3 OH group and the total number of OH substituents, respectively. These results have allowed the identification of the structural characteristics that promote vascular and antioxidant activity of flavonols, which may lead to the development of agents useful in treatment of cardiovascular disease.
Lowering of Elevated Ambulatory Blood Pressure by HMG-CoA Reductase Inhibitors
Authors: Terzoli Laura , Mircoli Luca , Raco Roberta , Ferrari Alberto U 
Published: August 2005

Abstract:

Controversial results were reported as to a possible blood pressure-lowering effect of statins. This may relate to methodological limitations (blood pressure measuring techniques) or to putative different effects of statins in different biologic conditions (cholesterol or blood pressure levels, age, etc). Patients with cholesterol >200 mg/dL and no previous statin treatment underwent 24-hour ambulatory blood pressure (ABP) monitoring and were classified as normotensives or hypertensives according to their ABP. They were randomized to statin (n = 51, simvastatin or pravastatin, 10-20 mg/d; atorvastatin, 5-10 mg/d) or control treatment (n = 23, soy lecithin, 20 g/d) for 2 months, after which ABP assessment was repeated. No consistent treatment-related reduction in ABP was observed in lecithin-treated patients (either hypertensives or normotensives) or in statin-treated normotensive patients (−0.7 ± 5.1/−1.0 ± 4.6 mm Hg, both P = ns). In contrast, statin-treated hypertensive patients showed lower systolic and diastolic blood pressure (−5.7 ± 5.8/−3.5 ± 3.9 mm Hg, both P < 0.001), the effect was entirely accounted for by reduced daytime values with no change in nighttime values, and it was unrelated to the concomitant statin-induced cholesterol reduction. Statins moderately but significantly lower blood pressure in patients with high (but not with normal) ABP; the effect is confined to the daytime period and is unrelated to the extent of the cholesterol lowering.
Hemodynamic Effect of Intracoronary Administration of Levosimendan in the Anesthetized Pig
Authors: Grossini E , Caimmi P P , Molinari C , Teodori G , Vacca G 
Published: August 2005

Abstract:

In this study the hemodynamic effects of intracoronary injection of levosimendan in anesthetized pigs and the mechanisms involved were examined. In 12 anesthetized pigs instrumented for measurement of heart rate (HR), aortic blood pressure (ABP), central venous pressure (CVP), left ventricular end-diastolic blood pressure, left ventricular contractility and relaxation, and mean coronary blood flow (CBF), levosimendan has been injected into the left anterior descending coronary artery at doses corresponding to the ones commonly used in clinics as bolus administration but adapted to the measured CBF. In a further 9 pigs levosimendan has been administered after the blockade of α and β adrenoceptors, muscarinic receptors, and coronary nitric oxide synthase (NOS) to investigate the action mechanism of the drug. The intracoronary bolus administration of doses of levosimendan corresponding to 12 and 24 μg/kg in 10 minutes exerted, respectively, CBF increases of 26.3% and 41.3% of the control values in the absence of changes in the other hemodynamic variables. The blockade of the autonomic nervous system did not prevent the coronary vasodilation, which was, however, abolished by the NOS inhibition. The intracoronary administration of levosimendan exerts positive effects on myocardial blood supply without changes in ABP, HR, CVP, or in myocardial kinetics. The coronary effects of levosimendan are related to NO production.