bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro Cytotoxicity of Three 4,9-Diazapyrenium Hydrogensulfate Derivatives on Different Human Tumor Cell Lines
Authors: Roknić S. , Glavaš-Obrovac Lj. , Karner I. , Piantanida I. , Žinić M. , Pavelić K. 
Published: April 2003

DNA intercalating agents interfere with DNA’s role as a template in replication and transcription by inserting an intercalator molecule between adjacent base pairs. We synthesized three potential novel intercalators, 4,9-diazapyrenium hydrogensulfate derivatives: 5,10-diphenyl-4,9-dimethyl-4,9-diazapyrenium hydrogensulfate (FDAP), 4,9-dimethyl-4,9-diazapyrenium hydrogensulfate (GDAP) and 2,4,7,9-tetramethyl-4,9-diazapyrenium hydrogensulfate (MDAP) and tested their biological effects in vitro on four human tumor cell lines (SKBr3: breast carcinoma, HeLa: cervical carcinoma, CaCo2: colon carcinoma and SW620: poorly differentiated cells from lymph node metastasis of colon carcinoma). Cytotoxic effects on cell growth and viability were determined using tetrazolium dye (MTT) assay. DNA synthesis and proliferation of treated cells were studied by the [<sup>3</sup>H]-thymidine incorporation test. DNA fragmentation was analyzed by agarose gel electrophoresis. The growth inhibitory effect was cell-specific and dose-dependent. The most pronounced antiproliferative effect was observed on SKBr3 cells for FDAP (10<sup>–5</sup> <i>M</i>) 91.8%, for MDAP (10<sup>–5</sup> <i>M</i>) 85.3% and on SW620 cells for GDAP (10<sup>–5</sup> <i>M</i>) 65.3%. The DNA ladder fragmentation of treated HeLa and SKBr3 cells, as a hallmark of apoptosis, was observed. Based on specific DNA fragmentation, morphological changes (reduced cell volume, round cell shape, condensed chromatin) and growth inhibition of treated human tumor cells we conclude that tested substances induced apoptotic cell death.
Polyamine Uptake Across the Basolateral Membrane of the Enterocyte Is Mediated by a High-Affinity Carrier
Authors: Milovic Vladan , Caspary Wolfgang F. , Stein Jürgen 
Published: April 2003

<b>Background/Aims:</b> Polyamine uptake from the circulation plays an important role in the maintenance of the intracellular polyamine content during extensive proliferation in intestinal mucosal cells. <b>Methods:</b> Isolated basolateral membrane vesicles of the rabbit enterocyte were used to characterize polyamine transport across the basolateral side of the intestinal epithelium. Incorporation of spermidine and spermine into the basolateral membrane was rapid, although 30–60% of polyamines were initially bound to the basolateral membrane. In order to avoid the influence of binding on the actual uptake into the vesicles, polyamine incorporation was measured at 37 and 4°C, and kinetic parameters were calculated from the difference in polyamine incorporation rates at these temperatures. <b>Results:</b> Uptake kinetics was saturable, with K<sub>m</sub> values of 13.34 and 12.35 µmol/l and V<sub>max</sub> of 159 and 105 pmol/mg protein/min for spermidine and spermine, respectively. It was also temperature dependent, with Q<sub>10</sub> values (calculated between uptake velocities at 37 and 25°C) of 2.56 for spermidine and 1.90 for spermine. At physiological pH, polyamine uptake was at its highest. Since at this pH polyamines are fully charged, charge might be essential for polyamines to be taken up across the basolateral membrane. Polyamine uptake was inhibited by di-, tri- and tetracations, and there was no evidence for sodium cotransport. Transport of putrescine was not inhibited by spermine and spermidine, although spermidine inhibited spermine uptake in a competitive manner, with K<sub>i</sub> of 127 µmol/l. <b>Conclusion:</b> These results imply that a saturable high-affinity transport system for polyamine does exist at the basolateral side of the enterocyte. Such a transport system may be responsible for the active transport of polyamine into rapidly proliferating enterocytes.
Implications of Tachykinins and Calcitonin Gene-Related Peptide in Inflammatory Bowel Disease
Authors: Holzer Peter 
Published: April 2003

Calcitonin gene-related peptide (CGRP) and the preprotachykinin A gene-derived peptides substance P (SP) and neurokinin A (NKA) are expressed in extrinsic primary afferent nerve fibres and intrinsic enteric neurons of the gut. The actions of tachykinins on the digestive effector systems are mediated by three different types of tachykinin receptor, termed NK<sub>1</sub>, NK<sub>2</sub> and NK<sub>3</sub> receptors, while the gastro-intestinal actions of CGRP are brought about by CGRP<sub>1</sub> and possibly other CGRP receptors. These neuropeptide transmitters are expressed by enteric neurons, intestinal muscle, epithelium and vascular system in a cell-specific manner and enable SP, NKA and CGRP to influence motility, electrolyte and fluid secretion, vascular and immune functions in a peptide- and region-specific fashion. Inflammatory disorders of various aetiology involve changes in the peptidergic innervation of the gut, and inflammatory bowel disease is associated with NK<sub>1</sub> receptor upregulation in intestinal blood vessels and lymphoid structures. Some of these alterations are reproduced in experimental models of gastro-intestinal disease, and there is mounting evidence that an imbalanced function of peptidergic neurons contributes to motor, secretory, vascular and immunological disturbances in intestinal anaphylaxis, infection and inflammation. In a therapeutic perspective it seems conceivable that tachykinin and CGRP receptors antagonists can be employed as spasmolytic, antidiarrhoeal, anti-inflammatory and antinociceptive drugs.
Influence of the Substrate on the Reproducibility of the Hydrogen Breath Test to Measure the Orocecal Transit Time
Authors: Casellas F. , Malagelada J.-R. 
Published: April 2003

<b>Background:</b> The H<sub>2</sub> breath test is widely used for the measurement of the orocecal transit time (OCTT). However, its clinical applicability is limited by its suboptimal reproducibility. <b>Aim:</b> To investigate whether changes in the substrate for the H<sub>2</sub> breath test improve its reliability for the measurement of the OCTT. <b>Methods:</b> 72 consecutive patients referred for measurement of the OCTT were studied. The breath test was performed twice, on consecutive days. One group of patients (‘lactulose + water’ group) received lactulose 13.3 g in water both days. Another group (‘lactulose + diet’) received lactulose 13.3 g in a liquid meal of 400 kcal. A third group (‘lactulose-lactitol’) received 13.2 g of lactulose the first day and 10 g lactitol the following day. The fourth group (‘lactitol + water’) received lactitol 10 g in water both days. Alveolar breath was sampled every 10 min for the next 3 h for H<sub>2</sub> chromatography. <b>Results:</b> OCTT in the first and second day test for the groups ‘lactulose + water’, ‘lactulose + diet’ and ‘lactitol + water’ were similar. In these three groups, the values obtained on the first and second day did not differ from 0 and were also significantly correlated. However, the correlation and the mean coefficient of variation were better in group ‘lactulose + water’ than in the groups ‘lactulose + diet’ and ‘lactitol + water’. In group ‘lactulose-lactitol’ the results on both days were significantly correlated although the delta between matched values was different from 0 (p = 0.03). <b>Conclusion:</b> The meal substrate influences the variability of the OCTT. However, reproducibility of the test does not improve with the addition of a liquid meal.
Oxidative Stress Affects Pancreatic Proteins during the Early Pathogenesis of Rat Caerulein Pancreatitis
Authors: Reinheckel Thomas , Prause Juliane , Nedelev Barbara , Augustin Wolfgang , Schulz Hans-Ulrich , Lippert Hans , Halangk Walter 
Published: April 2003

Rats received up to four subcutaneous injections of caerulein (20 µg/kg) in hourly intervals to induce a mild edematous pancreatitis. A single dose of caerulein resulted in significant oxidative modification of proteins in pancreatic homogenates as compared to saline-injected controls (p < 0.01). Repeated injections of the secretagogue were unable to induce a further increase in modified proteins. Protein oxidation preceded the formation of the lipid peroxidation product malondialdehyde as well as edema and the increase in serum amylase by 1–2.5 h. Western blotting for oxidatively modified proteins confirmed the results of the quantitative measurements and did not reveal individual, selectively modified proteins. These findings indicate that oxidative stress and oxidative protein modification are very early events in the initial period of caerulein pancreatitis. This may explain the poor success rate of most studies that administered antioxidants therapeutically during or after initiation of pancreatitis.
Comparison of the 1-Gram <sup>14</sup>C-<i>D</i>-Xylose Breath Test and the 50-Gram Hydrogen Glucose Breath Test for Diagnosis of Small Intestinal Bacterial Overgrowth
Authors: Stotzer Per-Ove , Kilander Anders F. 
Published: April 2003

<i>Background/Aims:</i> Culture of small bowel aspirate is the most direct method and the gold standard for diagnosing small intestinal bacterial overgrowth. However, cultures are cumbersome and fluoroscopy is required for obtaining aspirate. Therefore, different breath tests such as the xylose breath test and the hydrogen breath test have been developed. There is no general agreement as to which test is to be preferred. In the only previous direct comparison between these two tests an advantage for the 1-gram-<sup>14</sup>C-<i>D</i>-xylose breath test was found. The aim of the study was to compare the 50-gram glucose hydrogen breath test and the 1-gram <sup>14</sup>C-<i>D</i>-xylose breath test in relation to results of cultures of small bowel aspirate. <i>Methods:</i> Forty-six consecutive patients, mean age 57 (range 27–87) years, 12 men and 34 women, were included because of suspicion of small intestinal bacterial overgrowth. After small bowel aspiration, all patients received a solution of 1 g xylose, labelled with 50 µg <sup>14</sup>C-<i>D</i>-xylose, and 50 g glucose dissolved in 250 ml water. The concentration of breath hydrogen was analyzed every 15 min for 2 h and <sup>14</sup>CO<sub>2</sub> was analyzed every 30 min for 4 h. A positive hydrogen breath test was defined as a rise in hydrogen concentration of 15 ppm. A positive xylose test was defined as an accumulated dose 4.5% after 4 h. Two definitions for a positive culture were used, either growth of 10<sup>5 </sup>colonic-type bacteria/ml or growth of 10<sup>5</sup> bacteria/ml of any type. <i>Results:</i> Twenty-four patients had growth of 10<sup>5</sup> bacteria, of whom 10 had growth of 10<sup>5</sup> colonic-type bacteria in small bowel aspirate. Twenty-two patients had no significant growth. The hydrogen breath test and the xylose breath test had a sensitivity for growth of 10<sup>5</sup> bacteria of 58 and 42%, respectively. For growth of 10<sup>5 </sup>colonic-type bacteria the sensitivity was 90% for the hydrogen breath test and 70% for the xylose breath test. The specificity was similar for the two tests. <i>Conclusion:</i> Although no significant difference between the two tests was found, there was a tendency in favor of the 50-gram glucose hydrogen breath test. The simplicity in combination with high sensitivity makes the hydrogen breath test suitable as a screening method to select patients for further investigation.
Induction of Artificial Fat Maldigestion by Tetrahydrolipstatin Assessed by the <sup>13</sup>C-Hiolein Breath Test in Healthy Volunteers
Authors: Ashraf Hasan , Hildebrand Pius , Meier Remy , Beglinger Christoph , Gyr Niklaus 
Published: April 2003

<i>Background:</i> <sup>13</sup>C-hiolein is a purified algal triglyceride which is synthesized with 98% of all carbon atoms of the molecule uniformly <sup>13</sup>C-labeled. Orlistat is the new name for tetrahydrolipstatin (THL), which is a specific and potent inhibitor of gastrointestinal lipases which induces artificial fat malabsorption in humans. The aim of the present study was to use the <sup>13</sup>C-hiolein breath test (HBT) to assess THL-induced fat malabsorption in healthy volunteers. <i>Methods:</i> Eight healthy volunteers of normal body weight underwent 2 study periods of 4 days of diet with or without THL 120 mg t.i.d. On day 5, a HBT was performed. <sup>13</sup>CO<sub>2</sub> recovery in breath samples was measured over 24 h by isotope ratio mass spectrometry. <i>Results:</i> The peak <sup>13</sup>CO<sub>2</sub> excretion occurred only after 5 h in both treatment groups with little difference during the first 4 h between the groups. THL potently reduced fat digestion and absorption with the most pronounced effect observed after 8 h: 1.1± 0.2 vs. 2.3 ± 0.3% dose in control experiments (p < 0.05). The 24-hour cumulative <sup>13</sup>CO<sub>2</sub> excretion was also significantly reduced by THL: 14.9 ± 2.2 vs. 28.4 ± 4.1% dose in control experiments (p < 0.05). In 6 of the 8 subjects, the cumulative <sup>13</sup>CO<sub>2</sub> excretion was lower with THL 120 mg t.i.d. than with placebo. <i>Conclusion:</i> The HBT well reflects THL-induced artificial fat maldigestion in healthy volunteers.
Obstructive Jaundice, Bacterial Translocation and Interdigestive Small-Bowel Motility in Rats
Authors: Nieuwenhuijs Vincent B. , van Dijk Jaap E. , Gooszen Hein G. , Akkermans Louis M.A. 
Published: April 2003

<i>Background/Aims:</i> Translocation of gut bacteria occurs in obstructive jaundice, the underlying mechanisms are unclear. We designed this experimental study to investigate the association between interdigestive motility and the pathogenesis of bacterial translocation during biliary obstruction. <i>Methods:</i> Rats were fitted with jejunal myoelectrodes for the measurement of the interdigestive migrating motor complex (MMC) and with two cannulas in the proximal common bile duct (CBD) for exteriorization of biliary flow. This allowed measurement of MMCs under control conditions with an intact enterohepatic circulation and during 3 days of CBD obstruction without surgical intervention. Mesenteric lymph nodes, liver, spleen and segments of the duodenum, the jejunum and the caecum were removed for microbial culturing. <i>Results:</i> The MMC cycle length increased from 17.3 min before CBD obstruction to 31.9, 34.1, and 25.3 min on days 1, 2 and 3, respectively, after CBD obstruction (p < 0.05 for all days). Bacterial levels in the jejunum were significantly higher in CBD-obstructed rats than in control rats. The translocation incidence was significantly higher in rats with CBD obstruction (6/8) than in control rats (1/8). The bacterial levels in the jejunum correlated significantly with the MMC cycle length (r = 0.60, p <0.05). <i>Conclusion:</i> Experimental biliary obstruction is associated with disturbance of MMCs, small-bowel bacterial overgrowth and increased bacterial translocation.
Mitochondrial DNA Analysis in Ocular Myopathy
Authors: Vilarinho Laura , Santorelli Filippo M. , Cardoso Maria Luís , Coelho Teresa , Guimarães António , Coutinho Paula 
Published: April 2003

We analyzed 29 patients with progressive external ophthalmoparesis (PEO) either alone or as part of a multisystem disorder. Ragged-red fibers were very abundant (10–20%) in 15 patients, and many of them were also cytochrome c oxidase-negative. Biochemical analysis of the respiratory chain showed partial defects of single or multiple complexes in 18 patients (64%). Eleven PEO patients (38%) harbored single large-scale mtDNA deletions in muscle, which averaged 5.4 kb in size and 47% in relative abundance. One PEO patient harbored the A3243G mutation (MELAS mutation) in muscle (63%). Our findings, the first reported in Portuguese patients, confirm that single large-scale mtDNA deletions are a significant cause of PEO. Although ophthalmoparesis was the main clinical feature in the majority of patients, the clinical spectrum is broad, ranging from severe encephalopathy of childhood to a milder, though disabling, muscle weakness in adults.
Low-Dose Treatment of Cervical Dystonia, Blepharospasm and Facial Hemispasm with Albumin-Diluted Botulinum Toxin Type A under EMG Guidance
Authors: Rollnik Jens D. , Matzke Mike , Wohlfarth Kai , Dengler Reinhard , Bigalke Hans 
Published: April 2003

Several studies support the hypothesis that low-dose botulinum toxin treatment may be as beneficial as high-dose regimen. Therefore, we studied 115 patients (aged 27–84; mean 58.0, SD = 12.9 years; 68% females, 32% males) suffering from cervical dystonia (n = 66), blepharospasm (n = 28), and facial hemispasm (n = 21) over a period of 2 years in an open label, non-controlled pilot study. Patients received low-dose treatment with botulinum toxin type A (Dysport<sup>®</sup>). The toxin was diluted in 20 ml of 0.1% albumin solution to arrive at a concentration of 25 MU/ml and injected under EMG control. Patients responded to the treatment about 1 week after injection (mean 7.3 days, SD = 4.6). The mean duration of beneficial effects was 11.7 weeks (SD = 5.6). Patients evaluated the clinical global improvement on a scale ranging from 0 to 4. For the whole population, the mean was 2.7 points (SD = 1.1). In none of the subjects could antibodies to botulinum toxin type A be detected, and only a few side effects were observed. In conclusion, low-dose therapy with botulinum toxin A merits further controlled studies.
Preclinical Impairment of the Striatal Dopamine Transporter System in Sporadic Olivopontocerebellar Atrophy: Studied with [<sup>123</sup>I]β-CIT and SPECT
Authors: Kim Gyeong-Moon , Kim Sang Eun , Lee Won Yong 
Published: April 2003

We investigated whether the dopamine (DA) transporter system is impaired in sporadic olivopontocerebellar atrophy (sOPCA) patients without clinical parkinsonism using the DA transporter radiotracer [<sup>123</sup>I]β-CIT [2β-carboxymethoxy-3β-(4-iodophenyl)tropane] and single-photon emission computed tomography (SPECT). SPECT scans were acquired in 9 patients with sOPCA, 7 multiple system atrophy (MSA) patients with parkinsonism (MSA-P), and 7 age-matched healthy controls 20–24 h after the intravenous injection of [<sup>123</sup>I]β-CIT. [<sup>123</sup>I]β-CIT-specific binding in the striatum was determined as the radioactivity ratio of the striatum to the occipital cortex (specific binding ratio, SBR). In patients with sOPCA and MSA-P, SBRs in the right and left striatum and the mean SBR were significantly lower than those in controls (p < 0.05). The mean SBRs in patients with sOPCA and MSA-P were reduced to 69.0 and 60.7% of the control mean, respectively. However, there was no significant difference in SBRs between sOPCA and MSA-P patients. In sOPCA patients, the mean SBR was significantly correlated with the score of the clinical cerebellar function scale (r = –0.670, p = 0.024). These results indicate that even in the absence of clinical parkinsonism, the striatal dopaminergic system may be impaired in sOPCA. The DA transporter loss in sOPCA serves as another clue for sOPCA being a part of the spectrum of MSA.
Type I Sialidosis: A Clinical, Biochemical and Neuroradiological Study
Authors: Palmeri Silvia , Villanova Marcello , Malandrini Alessandro , van Diggelen Otto P. , Huijmans Jean G.M. , Ceuterick Chantal , Rufa Alessandra , DeFalco Danilo , Ciacci Giuseppe , Martin Jean J. , Guazzi Giancarlo 
Published: April 2003

We report biochemical, morphological and neuroradiological findings in a 40-year-old woman affected with type I sialidosis. The clinical symptoms, consisting of a cerebellar syndrome, were first noted at the age of 17 years. The macular cherry-red spot was first observed after 23 years of disease. A CT scan performed at 21 years of age showed enlargement of the fourth ventricle. Nuclear magnetic resonance imaging of the brain performed at the age of 40 showed severe atrophy of the cerebellum and pontine region; atrophy of cerebral hemispheres and of the corpus callosum was also observed. We emphasize the prolonged course of illness in this patient, observed over a long period of time. Of particular interest is the neuroradiological study showing our findings both at the beginning of the disease and after 20 years.
Blink Reflexes and Lateral Spreading in Patients with Synkinesia after Bell’s Palsy and in Hemifacial Spasm
Authors: Eekhof J.L.A. , Aramideh M. , Speelman J.D. , Devriese P.P. , Ongerboer de Visser B.W. 
Published: April 2003

We compared various electrodiagnostical tests in patients with hemifacial spasm and in patients who developed synkinesia after Bell’s palsy. We examined the evoked blink reflexes in the orbicularis oculi (o. oculi) and orbicularis oris (o. oris) muscles in 23 patients with hemifacial spasm (HFS), in 10 patients with synkinesia after Bell’s palsy (BPS) and in 22 control subjects. In the patient groups, we recorded synkinesia, latency and amplitude of compound muscle action potential (CMAP) in the mental muscle after stimulation of the facial nerve and we examined electromyographic activity of the o. oculi and mental muscles synchronously. Furthermore, we studied the phenomenon of lateral spreading, also known as ephaptic transmission, between the different facial nerve branches. Patients with BPS had a prolonged R1 latency on the affected side in o. oculi and smaller mental CMAP amplitude as an indication of facial nerve damage and nerve fiber loss. This was not found in patients with HFS, who showed an increased amplitude of the R1 and R2 responses in o. oris. Patients with BPS showed only an increased R1 amplitude in o. oris. All patients had signs of synkinesia. Lateral spreading with different patterns was present in all patients with HFS and in half of the patients with BPS. Latencies of early and late responses showed no differences between HFS and BPS. In addition to alterations in facial nucleus excitability in both conditions, ectopic re-excitation of facial nerve axons in HFS may explain the differences in neurophysiological findings between HFS and BPS patients. A loss of control following synaptic stripping may also be a contributing factor.
Shoulder, Elbow and Wrist Components of Physiologic Tremor Amplitudeas Measured Using a Laser Penlight
Authors: Davis Bradley J. , O’Connell John 
Published: April 2003

<i>Objective:</i> To measure the amplitude of physiological tremor in normal subjects using a novel method in an attempt to characterize some of the components of physiological tremor. <i>Background:</i> Current methods of measuring tremor are limited in their capability of measuring the contributions of various limb segments to physiologic tremor. <i>Design and Methods:</i> Subjects were asked to hold a laser penlight aimed at a target. Photographs with an exposure of 1 s were taken to record the path of the light. The angle of deflection was calculated under various conditions by averaging the results from four trials spaced at 15-second intervals. <i>Results and Conclusions:</i> The maximum amplitude under all conditions tested was less than 0.25°. Contributions from the wrist and fingers were significantly greater than contributions from the elbow or shoulder. Rotational movements were significantly more prominent than movements in other planes at the shoulder but not the elbow or wrist.