bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abdominal Surgery Decreases Food-reinforced Operant Responding in Rats
Authors: Martin Thomas J. , Kahn William R. , Eisenach James C. 
Published: August 2005

Background
Establishment of early oral nutrition after surgery is associated with a decrease in morbidity and mortality. The following studies were undertaken to determine how surgery influences food-reinforced behavior in rats and to determine the relevance of afferent input from the incision site on this behavior.

Methods
Rats were trained to press a lever for food pellets to assess the effects of various abdominal surgical manipulations. Operant requirements and food availability were also manipulated. The effects of wound infiltration with bupivacaine and denervation of the abdominal musculature in the area of the incision were similarly examined.

Results
Incision of the skin and abdominal musculature produced significant behavioral effects. Food pellets earned were significantly decreased, with gut manipulation producing effects of greater magnitude and duration than incision alone. Operant requirements or different schedules of food availability did not influence the effect of surgery on behavior. Infiltration of the wound with bupivacaine produced a reversal of the effects of surgery on behavior after skin and muscle incision but had minimal effects when the viscera were manipulated. Similarly, denervation of the abdominal musculature reversed the effects of abdominal incision on behavior.

Conclusions
Food maintained behavior is disrupted after laparotomy in rats. The time course and magnitude of this disruption, as well as its reversal by bupivacaine or denervation, are consistent with postoperative incisional pain. Manipulation of the viscera produces a greater effect than laparotomy alone, and additional mechanisms unrelated to incisional pain affect food reinforcement and feeding after surgery.
Possible Mechanism of the Vasodepressor Effect of Endokinin A/B in Anesthetized Rats
Authors: Abdelrahman Aly Mohamed , Syyong Harley , Tjahjadi Anindita , Pang Catherine Cheuk Ying 
Published: August 2005

Abstract:

We investigated the mechanism of the vasodepressor effect of endokinin A/B. An intravenous (IV) bolus of endokinin A/B (0.05-0.3 nmol/kg) dose-dependently decreased mean arterial pressure in thiobutabarbital-anesthetized rats. The magnitude of the response was unaffected by IV pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, inhibitor of nitric oxide synthase), methylene blue (inhibitor of soluble guanylyl cyclase), indomethacin (cyclooxygenase inhibitor), or tetraethylammonium (TEA, nonspecific K+ channel blocker). L-NAME reduced the half-recovery time of the vasodepressor effect of endokinin A/B relative to responses in rats pretreated with either saline or norepinephrine, which caused a similar pressor effect as did L-NAME. Methylene blue, but not TEA or indomethacin, reduced the recovery time of the vasodepressor effect of endokinin A/B. Therefore, the vasodepressor effect of endokinin A/B is mediated via the nitric oxide/L-arginine pathway and activation of soluble guanylyl cyclase but not by production of prostanoids or opening of TEA-sensitive K+ channels.
Negative Inotropic Effect of Low-Dose Ethanol in Mouse Ventricular Myocytes is Mediated by Activation of Endothelial Nitric Oxide Synthase
Authors: Zhang Shengjun , Grover Gary J , Stokes Henry , Scholz Peter M , Weiss Harvey R 
Published: August 2005

Abstract:

Low doses of ethanol can produce negative functional effects in ventricular myocytes. This may be related to the nitric oxide-cyclic GMP signal transduction system. We tested the hypothesis that ethanol stimulated endothelial nitric oxide synthase and this caused the negative functional effects in cardiac myocytes. This hypothesis was tested in ventricular myocytes isolated from endothelial nitric oxide synthase-knockout (eNOS−/−) and wild-type (WT) control mice. Cell function was determined with a video edge detector at 37°C. Myocytes were administered 5 or 10 mM ethanol alone or after 10−6 M L-nitro-arginine-methyl ester (L-NAME, nitric oxide synthase inhibitor) or 10−6 M 1H[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ, soluble guanylyl cyclase inhibitor). There were no differences in basal perecentage shortening (2.6 ± 0.2% WT versus 2.4 ± 0.2% eNOS) or maximal rate of shortening (44 ± 6 WT versus 47 ± 6 μms eNOS) between groups. In the WT mice, 10 mM ethanol significantly decreased percentage shortening (1.8 ± 0.1) and maximal rate of shortening (35 ± 4). These effects were blocked by L-NAME and ODQ. In the eNOS−/− mice, these values were not affected by ethanol. Similar data were seen for both maximal rate of shortening and relaxation. These data provide both pharmacological and direct genetic proof that these low doses of ethanol act as a stimulator of endothelial nitric oxide synthase, and this leads to the negative functional effects in ventricular myocytes.
Triple ACE-ECE-NEP Inhibition in Heart Failure: A Comparison With ACE and Dual ECE-NEP Inhibition
Authors: Mellin Virginie , Jeng Arco Y , Monteil Christelle , Renet Sylvanie , Henry Jean Paul , Thuillez Christian , Mulder Paul 
Published: August 2005

Abstract:

Mortality remains high in chronic heart failure (CHF) because under ACE inhibitor treatment other neurohumoral systems remain/become (de)activated, such as the endothelin and atrial natriuretic peptide pathways. Dual endothelin-converting enzyme-neutral endopeptidase (ECE-NEP) inhibition exerts beneficial effects in experimental CHF, but whether “triple” ACE-ECE-NEP inhibition is superior to ACE or ECE-NEP inhibition is unknown. We compared, in rats with CHF, ACE-ECE-NEP to ACE or ECE-NEP inhibition in terms of left ventricular (LV) hemodynamics and remodeling. Benazepril (2 mg/kg/d) or the ECE-NEP inhibitor CGS26303 (10 mg/kg/d) were administered alone or in combination (subcutaneously for 28 days starting 7 days after coronary ligation). ACE-ECE-NEP inhibition reduced blood pressure more markedly than ACE or ECE-NEP inhibition. All treatments increased cardiac output to the same extent, but ACE-ECE-NEP inhibition reduced LV diameter and LV end-diastolic pressure more markedly than ACE or ECE-NEP inhibition. The reduction of LV weight and collagen accumulation in the “viable” myocardium was most pronounced after ACE-ECE-NEP inhibition. These results, obtained in experimental CHF, illustrate a further improvement of LV hemodynamics and structure after ACE-ECE-NEP inhibition compared with either ACE or ECE-NEP inhibition, but whether this is associated with a further improvement of exercise tolerance and/or survival remains to be determined.
Induction of multicellular 3‐D spheroids of MCF‐7 breast carcinoma cells by neutrophil‐derived cathepsin G and elastase
Authors: Yui Satoru , Tomita Kazutaka , Kudo Tomoya , Ando Shingo , Yamazaki Masatoshi 
Published: August 2005

In tumor metastasis, multicellular aggregates of tumor cells form and disseminate into the blood or lymph vessels from the tumor mass, following the formation of tumor cell emboli in distant vessels. However, the mechanism by which aggregates form in the tumor mass is unknown. Neutrophils often exist in tumors and are considered to affect tumor development. We observed that neutrophils had the capacity to induce the aggregation of MCF‐7 human breast carcinoma cells adhering to culture substrates. When MCF‐7 cells were cultured with rat inflammatory neutrophils, the soluble fraction of their lysate, and the conditioned medium of neutrophils stimulated with N‐formyl‐Met‐Leu‐Phe plus cytochalasin B, multicellular aggregates formed within 16 h, and tightly aggregated 3‐D spheroids formed when the cultures were prolonged. The spheroid‐inducing reaction was reversible and energy‐dependent. The MCF‐7 cells induced to aggregate by the neutrophil extract showed growth potential, although the growth rate of the cells was slightly reduced. The aggregation was dependent on E‐cadherin, because the spheroids dispersed into isolated cells on incubation with EGTA or anti‐E‐cadherin antibody following pipetting. The aggregation‐inducing activity in neutrophils was completely inhibited by soybean trypsin‐chymotrypsin inhibitor. Moreover, the commercially available human neutrophil elastase and cathepsin G induced the aggregation of MCF‐7 cells and formation of spheroids. The proteases secreted by infiltrated neutrophils in tumors are implicated in the dissemination of tumor aggregates from primary tumor sites. (Cancer Sci 2005; 96: 560 –570)
Ubiquitin targeting of rat muscle proteins during short periods of unloading
Authors: Vermaelen M. , Marini J.‐F. , Chopard A. , Benyamin Y. , Mercier J. , Astier C. 
Published: August 2005

AbstractAim:  The ubiquitin‐proteasome system is known to be involved in many situations leading to skeletal muscle atrophy. However, the cellular mechanisms triggering the atrophic process initiation are still poorly understood. For short periods of rat hindlimb unloading, we assessed the specific ubiquitin targeting of sarcoplasmic or myofibrillar proteins in slow and fast rat muscle types.Methods:  Adult Sprague Dawley rats were randomly assigned to three groups: control, hindlimb‐unloaded for 4 days (HU4) and hindlimb‐unloaded for 8 days (HU8). In fractionated extracts from soleus (SOL) and Extensor Digitorum Longus (EDL) muscles, the relative contents of free and conjugated ubiquitin were quantified by immunoblotting.Results:  Hindlimb unloading of short durations resulted in a preferential atrophy of slow‐twitch fibres and bound ubiquitin levels were increased by 37 and 68% in the soleus myofibrillar fraction after respectively 4 and 8 days. The ubiquitin conjugation was shown to principally affect the high molecular weight proteins. Free and conjugated ubiquitin levels remained unchanged in sarcoplasmic fraction from SOL muscle after 8 days HU. For the fast muscle (EDL), ubiquitin contents were approximately twofold lower in control conditions, and did not significantly change during the hindlimb unloading periods considered.Conclusion:  The postural SOL muscle was shown to contain higher constitutive sarcoplasmic ubiquitin levels than the phasic EDL. The high response to unloading of the slow twitch fibres rich SOL muscle was accompanied by a specific conjugation of its myofibrillar proteins that may participate in the initiation of skeletal muscle remodelling consequent to disuse.
Doublets and low‐frequency fatigue in potentiated human muscle
Authors: Bentley L. F. , Lehman S. L. 
Published: August 2005

AbstractAim:  To test the hypothesis that doublets compensate for low‐frequency fatigue. Doublets increase force output from muscles stimulated at low frequencies. Low‐frequency fatigue is a decline in the force elicited by low‐frequency stimulation.Methods:  Human flexor carpi radialis muscles were stimulated with 20 Hz trains with and without an initial doublet and with and without low‐frequency fatigue and the resulting force response measured.Results:  An initial doublet caused an increase in the maximum rate of force rise of 179.6 ± 27.9% in rested and 242.9 ± 37.7% in muscles with low‐frequency fatigue, and a substantial enhancement in force in the first three inter‐pulse intervals after the extra pulse. The magnitude and time course of the early doublet enhancement were very similar regardless of low‐frequency fatigue, consistent with current theories regarding the mechanisms of the doublet effect and of low‐frequency fatigue. By the end of the 1 s stimulus train, force enhancement was insignificant in rested muscles and was small and subject‐dependent in muscles with low‐frequency fatigue (17.3 ± 8.1% of force without a doublet), reducing the force deficit by 25.2 ± 5.5%.Conclusions:  The time course of doublet force enhancement implies that an initial doublet may effectively compensate for the deficit in rate of force rise in muscles with low‐frequency fatigue, but may not compensate for force deficits beyond the first few inter‐pulse intervals.
Effects of 84‐days of bedrest and resistance training on single muscle fibre myosin heavy chain distribution in human vastus lateralis and soleus muscles
Authors: Gallagher P. , Trappe S. , Harber M. , Creer A. , Mazzetti S. , Trappe T. , Alkner B. , Tesch P. 
Published: August 2005

AbstractAim:  This investigation determined the effects of 84 days of bedrest on the composition of myosin heavy chain (MHC) in single skeletal muscle fibres with and without a resistance‐training countermeasure programme.Methods:  Muscle biopsies were obtained from the m. vastus lateralis (VL) and m. soleus (SOL) before and after 84 days of bedrest. While control (BR) subjects (VL n = 9; SOL n = 3) refrained from exercise, BRE subjects (VL n = 8; SOL n = 3) performed knee extensor and plantar flexor resistance exercise every third day. Approximately 110 fibres per sample were analysed for MHC composition using SDS‐PAGE.Results:  BR–VL had 16 and 14% decreases (P < 0.05) in MHC I and IIa fibres, respectively. There were 10% increases (P < 0.05) in MHC I/IIa, IIa/IIx, I/IIa/IIx, and a ∼30% increase (P < 0.05) in total hybrid fibres. BRE‐VL showed a 15% reduction (P < 0.05) in MHC I fibres, no change in MHC IIa fibres, and a 13% increase (P < 0.05) in total hybrids. BR–SOL had a 19% decrease (P < 0.05) in MHC I fibres with a 22% increase in total hybrids. BRE–SOL showed no change in MHC composition across all fibre types.Conclusion:  These data suggest that the exercise countermeasures programme prevented MHC shifts in the SOL and mitigated MHC shifts in the VL. Furthermore, in the VL it appears that the resistance training programme employed in this investigation during bedrest, emphasized the use of MHC IIa phenotype muscle fibres.
Acute myocardial ischaemia induces specific alterations of ventricular mitochondrial function in experimental pigs
Authors: Zoll J. , Ponsot E. , Doutreleau S. , Mettauer B. , Piquard F. , Mazzucotelli J. P. , Diemunsch P. , Geny B. 
Published: August 2005

AbstractAims:  As cardiac metabolic flexibility is crucial, this study examined whether acute ischaemia can induce specific qualitative alterations of the mitochondrial metabolic pathways as well as energy transfer systems.Methods:  Left descending coronary artery ligation was performed after sternotomy in eight pigs and the heart was excised after 45 min of ischaemia. Maximal O2 uptake (Vmax, μmol O2 min−1 g−1 dry weight) of saponin‐skinned myofibres were measured from ischaemic and non‐ischaemic area of ventricular myocardium.Results:  V
max decreased by ∼20% in ischaemic myocardium with both glutamate‐malate (18.1 ± 1.3 vs. 22.1 ± 1.7 in control, P < 0.05) and pyruvate substrates (19.3 ± 1.0 vs. 23.3 ± 2.0 in control, P < 0.05) whereas no difference was observed with palmitoyl carnitine (15.6 ± 1.8 vs. 16.6 ± 0.9 in control). The Km of mitochondrial respiration for ADP decreased in ischaemic heart by 24% (679 ± 79 vs. 899 ± 84 μm of ADP in control, P < 0.05). Moreover, the mitochondrial creatine kinase efficacy (Km without creatine/Km with creatine), representative of the coupling of oxidative phosphorylation process with the mitochondrial creatine kinase, was reduced in ischaemic heart (11.6 ± 2.5 in ischaemic vs. 18.0 ± 2.2 in control, P < 0.05).Conclusions:  These findings argue for specific mitochondrial impairments at the level of pyruvate oxidation and creatine kinase channelling system after an acute period of in vivo ischaemia, whereas the lipid mitochondrial oxidation pathway seems to be preserved. Such a loss of metabolic flexibility following acute ischaemia could become an early feature of metabolic dysregulation of the heart.
Acute exercise causes an enhancement of tissue renin–angiotensin system in the kidney in rats
Authors: Maeda S. , Iemitsu M. , Jesmin S. , Miyauchi T. 
Published: August 2005

AbstractAims:  Initially, the renin–angiotensin system (RAS) produced through the classical endocrine pathway was well known for its regulation of blood pressure. However, it was revealed that a local autocrine and/or paracrine RAS may exist in a number of tissues (such as kidney). Exercise causes a redistribution of tissue blood flow, by which the blood flow is greatly increased in active muscles, whereas it is decreased in the splanchnic circulation (such as in the kidney). We hypothesized that exercise causes an enhancement of tissue RAS in the kidney.Methods:  We studied whether exercise affects expression of angiotensinogen and angiotensin‐converting enzyme (ACE) and tissue angiotensin II level in the kidney. The rats performed treadmill running for 30‐min. Immediately after this exercise, kidney was quickly removed. Control rats remained at rest during this 30‐min period.Results:  The expression of angiotensinogen mRNA in the kidney was markedly higher in the exercise rats than in the control rats. ACE mRNA in the kidney was significantly higher in the exercise rats than in the control rats. Western blot analysis confirmed significant upregulation of ACE protein in the kidney after exercise. Tissue angiotensin II level was also increased by exercise.Conclusion:  The present study suggests that the exercise‐induced enhancement of tissue RAS in the kidney causes vasoconstriction and hence decreases blood flow in the kidney, which are helpful in increasing blood flow in active muscles, thereby contributing to the redistribution of blood flow during exercise.
Biliary secretion of moxifloxacin in obstructive cholangitis and the non‐obstructed biliary tract
Authors: SCHWAB D. , GRAUER M. , HAHN E. G. , MÜHLDORFER S. 
Published: August 2005

SummaryBackground : Biliary secretion of antibiotic agents into the bile is considerably compromised by biliary obstruction, a precondition of bacterial cholangitis. Moxifloxacin may be advantageous according to secretion and antimicrobial spectrum.Aim : To establish the secretion of moxifloxacin into obstructed and non‐obstructed bile.Methods : Biliary excretion of moxifloxacin was determined in plasma and bile of 10 patients with biliary obstruction and cholangitis and 10 patients without biliary obstruction 30 min after administration of 400 mg of moxifloxacin intravenously.Results : The plasma concentration of moxifloxacin was similar in both groups (4.45 ± 1.58 μg/mL; 4.33 ± 1.23 μg/mL). The concentration of moxifloxacin in the bile was significantly lower in patients with biliary obstruction than without (4.63 ± 3.94 μg/mL; range 0.71–14.40; vs. 16.90 ± 13.77 μg/mL; range 1.79–42.50; P = 0.043). Although significantly different, the penetration index was extensively high in those without biliary obstruction (4.41 ± 4.40; range 0.35–14.45) but still sufficient in those patients with obstructive cholangitis (1.02 ± 0.74; range 0.29–2.83; P = 0.035).Conclusion : These findings are suggestive of an active secretion mechanism for moxifloxacin into the obstructed bile, producing a biliary concentration sufficiently above the minimal inhibitory concentrations for most of the expected bacteria.
Colonic spread and serum pharmacokinetics of budesonide foam in patients with mildly to moderately active ulcerative colitis
Authors: BRUNNER M. , VOGELSANG H. , GREINWALD R. , KLETTER K. , KVATERNIK H. , SCHROLNBERGER C. , EICHLER H.‐G. , BRUNNER H. , DUDCZAK R. , MÜLLER M. 
Published: August 2005

SummaryBackground : Local treatment with foams in patients suffering from ulcerative proctitis or proctosigmoiditis is considered a rational treatment option.Aims : To investigate colonic spread, safety, tolerability and acceptance of a newly developed budesonide foam formulation.Methods : Twelve patients (four females, eight males) with acute proctosigmoiditis or left‐sided ulcerative colitis were rectally administered a single dose of [99Tcm]‐labelled budesonide foam (Budenofalk; Dr Falk Pharma GmbH, Freiburg, Germany) containing 2 mg budesonide in 20 mL foam after diagnostic colonoscopy. Thereafter, the colonic spread was assessed by means of γ‐scintigraphy for 6 h. Serum samples were taken simultaneously.Results : Budesonide foam spread with a maximum between 11 and 40 cm, thus reaching the sigmoid colon in all patients. In some patients, the foam even extended into the distal third and the middle of the descending colon with maximum radioactivity at 4 h. Systemic budesonide absorption was rapid and pharmacokinetic data were comparable with published data on marketed budesonide enemas, with mean serum Cmax and AUC0‐8h values of 0.8 ± 0.5 ng/mL and 3.7 ± 1.9 ng h/mL, respectively. The new formulation was well accepted by all patients, who could retain the foam for at least 4 h.Conclusions : In the majority of patients, budesonide foam effectively spread up to the left‐sided colon and thus qualifies for the local treatment of proctosigmoiditis.
Autoantibody profile during short‐term infliximab treatment for Crohn's disease: a prospective cohort study
Authors: ATZENI F. , ARDIZZONE S. , SARZI‐PUTTINI P. , COLOMBO E. , MACONI G. , DE PORTU S. , CARRABBA M. , BIANCHI PORRO G. 
Published: August 2005

SummaryBackground : The potential clinical implications of autoimmunity during treatment with infliximab are unclear.Aim : To determine the frequency and correlation of autoantibody formation in patients with Crohn's disease treated with infliximab in a routine clinical setting.Methods : Sixty‐three patients with refractory/inflammatory (31) and/or fistulising Crohn's disease (32), received an infliximab infusion at a dose 5 mg/kg in weeks 0, 2 and 6, and were evaluated for the development of antinuclear, anti‐double‐stranded DNA, anti‐Sm, anti‐RNP, anti‐SSA, anti‐SSB and antihistone antibodies. The correlates with pharmacological treatments, the response to infliximab and adverse events were evaluated.Results : Antinuclear antibodies were found in five of the 63 patients (8%) at baseline and in 26 (42%) after 10 weeks (P < 0.001). Of the 26 antinuclear antibody‐positive patients who were further subtyped, nine of 63 (17%) had anti‐double‐stranded DNA (P = 0.003), and 1.5% were extractable nuclear antigen (ENA) and antihistone‐positive. Five patients were initially positive for anticardiolipin antibodies and two more patients became positive during infliximab treatment. New autoantibody formation was more frequent in the patients with inflammatory/refractory disease than in those with fistulising disease (17 vs. 7; P = 0.02). One patient developed drug‐induced lupus without major organ damage.Conclusions : Autoantibody formation occurs in 42% of patients (8% of these patients were positive before infliximab treatment) with Crohn's disease receiving induction treatment with infliximab, but the clinical significance of this remains to be determined.