bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in Nasal Reactivity in Patients with Rhinitis medicamentosa after Treatment with Fluticasone Propionate and Placebo Nasal Spray
Authors: Graf Peter M. , Hallén Hans 
Published: April 2003

<b>Aim of the Study: </b>To study the changes in nasal reactivity in patients with rhinitis medicamentosa during treatment with placebo or fluticasone propionate, in order to better understand the mechanisms of nasal congestion in such patients. <b>Study Design: </b>A parallel, double-blind study. Twenty patients with rhinitis medicamentosa were randomized to either placebo or fluticasone treatment during 14 days. <b>Material and Methods: </b>Nasal mucosa reactivity was studied with a histamine challenge model using three concentrations of histamine to challenge the nasal mucosa (1, 2 and 4 mg histamine/ml). Recordings of the nasal mucosa response were made 5 min after each challenge, using rhinostereometry and acoustic rhinometry, before and after the period of treatment. <b>Results: </b>The fluticasone group had a significantly increased histamine sensitivity after treatment, unlike the placebo group who had an unchanged or slightly decreased histamine sensitivity after treatment. <b>Conclusions: </b>The results of this study support the theory that the nasal obstruction in rhinitis medicamentosa is due to interstitial oedema rather than to vasodilatation. On the first day of vasoconstrictor withdrawal, the inferior concha was congested and oedematous with a limited capacity to respond to histamine challenge. However, after 14 days of treatment with a corticosteroid nasal spray, the oedema was reduced and the increase in histamine sensitivity reflected the persistence of nasal hyperrreactivity. In the placebo group, histamine sensitivity remains unchanged with the measuring technique we used. This probably indicates that oedema was still present after treatment.
Vibration-Induced Nystagmus – A Sign of Unilateral Vestibular Deficit
Authors: Hamann Karl-Friedrich , Schuster Elke-Maria 
Published: April 2003

Vibrations of 60 Hz and 100 Hz were applied on the mastoid of healthy subjects, patients with unilateral peripheral vestibular lesions, with central lesions of different localizations, and patients with benign paroxysmal positioning vertigo (BPPV). In patients with unilateral peripheral deficit a horizontal nystagmus with a small torsional component beating generally to the not affected side could be observed. This nystagmus did not show adaptation during 40 s. The occurrence was more frequent using 60-Hz stimulations. This vibration-induced nystagmus did never occur in healthy subjects, seldom in patients with central vertigo, and only exceptionally in patients with BPPV. It is concluded that the finding of a vibration-induced nystagmus reflects a side difference of peripheral vestibular excitability.
Alteration of the Calcium Content in Inner Hair Cells of the Cochlea of the Guinea Pig after Acute Noise Trauma with and without Application of the Organic Calcium Channel Blocker Diltiazem
Authors: Maurer Jan , Heinrich Ulf-Rüdiger , Hinni MichaelL. , Mann Wolf 
Published: April 2003

Calcium ions are known to be important to the process of signal transduction across the apical and basal sides of the inner hair cells. Calcium channel antagonists have been demonstrated by light microscopy to provide protection against acoustic trauma. To evaluate the protective effect of calcium channel blocker on the inner ear cells to noise exposure, the amount of the histochemical reaction products formed in the cytoplasm of the inner hair cells of the guinea pig after application of pyroantimonate was measured by an image processing system connected to an energy-filtering transmission electron microscope (EFTEM). Compared to untreated control specimens (experimental animal group I) the amount of precipitable calcium had clearly increased in the inner hair cells of noise-exposed cochleae 60 h after an acute noise trauma (group III). In addition, small electron- lucent areas could be identified in the cytoplasm of the hair cells probably representing damage to the cellular fine structure. When the calcium channel blocker diltiazem was administered without any additional noise exposure the calcium content was drastically reduced in the inner hair cells (group II), but when the antagonist was given before and after acute noise trauma (group IV), the calcium content in the inner hair cells was nearly compared to the amount determined in the untreated group of animals. The role of diltiazem is discussed in respect of tissue protection and to the maintenance of the calcium-dependent physiological processes in the inner hair cells during signal transduction.
Age-Related Hearing Changes and Effects of Exotoxin on Inner Ear Function in Aging Rat
Authors: Stenqvist Monika 
Published: April 2003

Frequency-specific auditory brainstem responses to tone bursts (2–31.5 kHz) and tuning curves were recorded in 8 male rats during their entire life. No significant threshold elevation occurred during the 1st year. Mean age at onset of hearing loss was 20 months, with individual variations ranging from 14 up to 23 months. In most animals, threshold elevations were limited to 20 and 31.5 kHz. At age of 18–23 months, 3 rats were treated with <i>Pseudomonas aeruginosa</i> exotoxin A. After instillation, threshold elevation occurred at all frequencies, followed by near-total recovery at low frequencies, but only partial reversibility at high frequencies. It is concluded that aging-related hearing changes in Sprague-Dawley albino rats start at different ages, particularly comprising high frequencies and encroaching on the middle and low areas with increasing age.
Rhinocerebral Mucormycosis
Authors: Smilek P. , Čada K. , Wotke J. 
Published: April 2003

Recently, the incidence of opportunistic fungal infections has increased due to a rise in conditions with a general impairment of immunity. These are serious disorders that can be diagnosed and treated with difficulty and have an unfavourable prognosis. A case of a 45-year-old diabetic patient with late determination of rhinocerebral mucormycosis of peracute course and fatal termination is presented. The patient was treated with surgery and antibiotics, and the diagnosis was established postmortem. If rhinocerebral mucormycosis is suspected (immunodeficiency, temperatures which do not respond to antibiotic treatment, black crusts in the nose, unilateral headache, symptoms of orbitocellulitis and endocranial complications), a biopsy must be taken from the margin of a necrotic lesion. If non-septated hyphae with rectangular branching are found, it is necessary to start a complete therapy attempting to adjust the general condition, aggressive surgical debridement and the intravenous administration of amphotericin B at a dose of 0.25–0.30 mg/kg/day or the liposomal form of amphotericin B, 3–4 mg/kg/day, at first daily, then every other day.
Schalldruckpegelmessungen und Impulsdauerbestimmungen handelsüblicher Schreckschusswaffen
Authors: Just T. , Kramp B. , Pau H.W. , Sievert U. , Wild W. , Kunde B. , Schilf M. 
Published: April 2003

<b>Fragestellung:</b> Ziel der Untersuchung war es, die Schalldruckpegel einiger im Handel frei erhältlicher Schreckschusswaffen sowie die Impulsdauer unter realen Schiessbedingungen in einer Schiesshalle zu bestimmen. <b>Material und Methoden:</b> Es wurden 6 verschiedene Schreckschusswaffen mit zwei verschiedenen Kalibern untersucht. Um die Schalldruckpegel am rechten Ohr des Schützen zu messen, wurde die Waffe im Abstand von 80 cm im Winkel von 180°, 225° und 135° zum Mikrofon gehalten. Zur Bestimmung der Schalldruckpegel bei direkt vor das Ohr gehaltener Waffe wird die Waffenmündung in der Horizontalebene in Winkeln von 0°, 45° und 90° aus 1,5–2 m Entfernung vor das Mikrofon gehalten. Der Signalverlauf der impulshaltigen Schallereignisse wurde graphisch dargestellt. <b>Ergebnisse und Schlussfolgerungen:</b> Die Schalldruckpegel lagen bei direkt auf das Ohr gerichteter Waffe (0°) aus 1,5 m Entfernung zwischen 155 und 157 dB. Bei der Variation des Winkels von der Waffenmündung zum Ohr (45°, 90°) wurden Spitzenschalldruckpegel über 150 dB gemessen. Die am rechten Ohr des Schützen (180°) gemessenen Spitzenschalldruckpegel lagen zwischen 140 und 150 dB. Die 135°- und 225°-Messungen zeigten eine starke Richtungswirkung der Schreckschusswaffen. Bei Rechtsdrehung in der horizontalen Ebene (135°) ermittelten wir erwartungsgemäss um 1–6 dB höhere Spitzenschalldruckpegel. Die Effektivwerte (quadratische Mittelwerte) des gesamten Impulses waren im Durchschnitt 4–10 dB niedriger als die Spitzenschalldruckpegel. Die Impulsdauer belief sich bei allen Waffentypen auf Werte unter 2 ms. Impulse von handelsüblichen Schreckschusswaffen zeigen also vergleichbar hohe Spitzenschalldruckpegel wie die von Revolvern und Pistolen mit «scharfer» Munition. Knalltraumata dieser Genese können zu einem Hörverlust im Hochtonbereich führen, der langandauernd, sogar bleibend sein kann. In welchem Zeitraum mit Besserungen zu rechnen ist, hängt nicht zuletzt von der Vorschädigung des Ohres sowie von der Entfernung und vom Winkel der Waffenmündung zum Ohr ab.
Changes in Matrix Metalloproteinases during the Evolution of Interstitial Renal Fibrosis in a Rat Experimental Model
Authors: González-Avila Georgina , Iturria Cecilia , Vadillo-Ortega Felipe , Ovalle Consuelo , Montaño Martha 
Published: April 2003

The aim of the present study was to analyze the matrix metalloproteinase (MMP) activity during the evolution of interstitial renal fibrosis in a rat experimental model of unilateral ureteral obstruction. The interstitial type I collagenase and the gelatinolytic activities were analyzed by radiolabeled substrate degradation. Interstitial collagenase activity was low at all times while gelatinolytic activity increased on day 6 of evolution, with a decrease in activity from this point. The use of organomercurials revealed the presence of latent enzyme in all cases. Normal kidney samples contained MMP-9 in both active and proenzyme forms as revealed by zymography. On day 3 MMP-9 dimers appeared, and increased activity was observed until day 6. A decrease in the gelatinolytic activity was detected from days 9–15 of evolution. This observation was confirmed by Western blot analysis that revealed the presence of proMMP-9 mainly from days 6–12. Tissue inhibitor of metalloproteinase-1 (TIMP-1) was also detected alone and in combination with proMMP-1 and MMP-1, particularly from days 6–15 of evolution. The presence of MMP-9 and MMP-1 was detected in the cytoplasm of cortical tubular cells by immunohistochemistry, with no difference between the experimental and the normal kidneys. There was also an increase in collagen concentration from day 3 after surgery that increased during the entire evolution of the experimental model. This work reveals that the decrease in the MMP-9 and MMP-1 enzymatic activity, due to their interaction with TIMP-1 and to the lack of activation of the latent forms, may participate in the excessive collagen deposit during the evolution of experimental interstitial renal fibrosis.
Short-Term Culturing Influences the Number of bcr/abl-Fused Cells Detected by Fluorescence in situ Hybridisation in Bone Marrow Aspirates of CML Patients
Authors: Wilkens Ludwig , Varga Sabine , Werner Martin , Nolte Martina , v. Wasielewski Reinhard , Georgii Axel 
Published: April 2003

Fluorescence in situ hybridisation (FISH) has been proven as a helpful tool in diagnosis and monitoring of bcr/abl fusion in chronic myelogeneous leukaemia (CML). Since long-term cultures are known to decrease the number of bcr/abl-fused cells, it is questionable whether similar effects are detectable in short-term cultures, a technique often preceding FISH analysis. Therefore, we evaluated bone marrow aspirates of 10 CML patients at biopsy and after culturing for between 24 and 144 h by FISH. The percentage of bcr/abl-fused cells in FISH varied between 15 and 70% at biopsy. In samples with 15 and 30% of aberrant cells at biopsy, an increase of about 20% per day was seen within the first 48 h. In longer lasting cultures, the percentage of leukaemic cells then asymptotically approached a value of 60–70%. In patients with 38 and 50% of bcr/abl-fused cells at biopsy, an increase of about 20% could be detected in the first 24 h. Then 65–70% of the cells already bore the bcr/abl fusion, and the percentage of leukaemic cells was almost constant for longer lasting cultures up to 144 h. In patients with a percentage of about 70% before culturing, no increase in positive cells was detected. These results emphasize the impact of short-term culturing on the number of bcr/abl-fused cells. In particular, the importance for monitoring CML patients is obvious. Therefore the effect described should be taken into account in order to avoid misinterpretation and incorrect therapy decisions in CML patients.
Induction of Tolerance in Macrophages by Cholera Toxin B Chain
Authors: Burkart Volker , Kim Yoong-Eun , Kauer Manfred , Kolb Hubert 
Published: April 2003

Model systems of human type 1 diabetes have revealed an important role of cellular immune reactions involving macrophages and T cells in the destruction of autologous insulin-producing pancreatic β cells. Recently, the cholera toxin B chain (CTB) was found to suppress T cell-dependent autoimmune diseases including autoimmune diabetes of nonobese diabetic mice. Therefore, we tested the hypothesis that CTB exerts much of its immunomodulatory activity by targeting macrophages. These studies are reviewed here. Cells of the human monocyte line Mono Mac 6 were exposed to CTB and subsequently tested for proinflammatory immunoreactivity in response to challenge with endotoxin (LPS from <i>Escherichia coli</i>, 10 ng/ml for 5 h). Incubation of monocytes with CTB (10 μg/ml) suppressed a later proinflammatory response to LPS as demonstrated by suppression of TNFα release from 6.7 ± 0.7 ng/ml in cultures without CTB preexposure to 1.8 ± 1.1 ng/ml in CTB-pretreated cells (p < 0.001). In contrast, the release of IL-10 remained inducible after CTB pretreatment. RT-PCR analysis showed that the suppression of TNFα production occurred at the level of mRNA formation. Control experiments excluded a role of possible contamination of CTB by endotoxin or the intact cholera toxin. Tolerance induction was maximal after 5 h of CTB exposure and persisted for 24 h. The suppressive effect of CTB was dose-dependent and no more recognizable at ≤1 μg/ml. Incubation with IL-10- and TGFβ-neutralizing antibodies during CTB pretreatment prevented tolerization of macrophages. IFNγ (1,200 U/ml) was found to antagonize actions of CTB. In contrast to desensitization by low doses of LPS, tolerance induction by CTB occurred ‘silently’, i.e. in the absence of a measurable proinflammatory response. In view of the potent instructive role of the innate immune system on T cell responses these findings are important in understanding how CTB prevents the development of autoimmune diabetes and improves tolerance to islet autoantigens.
Changes in Brain Neurofilament and Beta-Tubulin Proteins after Cerebral Hypoxia-Ischemia in Rabbits
Authors: Mink Richard B. , Johnston Jill A. 
Published: April 2003

Neurofilaments (NF) and tubulin are highly phosphorylated proteins that are important in neuronal structure and function. Changes in phosphorylation alter their antigenicity, and previous studies examining the effect of ischemia on these proteins failed to consider this factor. Using phosphate-independent antibodies and a quantitative immunoassay, we examined whether the amount of NF 68-kD (NF 68), NF 160-kD (NF 160), NF 200-kD (NF 200) and class III β-tubulin proteins in the brain are reduced after cerebral injury. Rabbits were subjected to 8 min of hypoxia and then to 8 min of ischemia. After 4 h of reperfusion, NF 68 decreased from an overall group mean (± SEM) of 17.5 ± 2.3 ng NF 68 μg/total protein in the noninjured controls (n = 8) to 12.9 ± 1.2 ng/μg total protein in the hypoxic-ischemic group (n = 9). Conversely, NF 200 increased from 31.6 ± 3.3 ng/μg in controls to 47.7 ± 3.2 ng/μg. The amount of NF 160 and β-tubulin was unchanged. The response of the NF proteins to brain injury is more complicated than described previously. Additional studies examining the regulation and metabolism of the NF are warranted, especially regarding the role of phosphorylation.
Differences in pH-Dependent Activation Rates of Substituted Benzimidazoles and Biological in vitro Correlates
Authors: Kromer W. , Krüger U. , Huber R. , Hartmann M. , Steinijans V.W. 
Published: April 2003

Gastric proton pump inhibitors (PPIs) are substituted benzimidazole prodrugs that require an acid-induced activation. Its rate depends on the reactivity of the molecule relative to the environmental pH and determines the drug’s tissue selectivity. Factors affecting the exposure of moderately acidic tissues to the activated PPI are the area under the serum concentration-time curve (AUC), serum protein binding, the partition coefficient logP and the serum elimination half-life relative to the chemical activation half-life at a critical tissue pH of about 5. These parameters have therefore been determined in a comparative fashion in the present study. The data shows that pantoprazole is less likely to undergo unwanted activation at moderately acidic targets as opposed to the parietal cell, compared to omeprazole. Actually, although 40 mg pantoprazole (steady state) gave a slightly higher serum AUC of the total parent compound than 40 mg omeprazole (10.5 vs. 7.1 µmol × h × l<sup>–1</sup>), a higher serum protein binding of pantoprazole versus omeprazole (98 vs. 96%) reversed the AUC values for the free drug in favor of a lower value for pantoprazole (0.19 vs. 0.28 µmol × h × 1<sup>–1</sup>). It is the free parent compound that equilibrates across cell membranes to be activated in acidic tissue compartments. At pH 5.1, the activation half-life of pantoprazole was 4.7 versus 1.4 h for omeprazole, the latter being in the order of the common serum elimination half-life determined in an intraindividual comparison (1.24 vs. 1.25 h). Thus, pantoprazole is eliminated faster from blood than it is activated at a pH of about 5, while omeprazole is as quickly activated at this pH as it is eliminated from blood. Biological in vitro experiments confirmed that pantoprazole displays a lower liability to interfere with unwanted biological targets. This has been demonstrated in vitro for inhibition of both renal Na<sup>+</sup>/K<sup>+</sup>-ATPase, lysosomal acidification and the production of reactive oxygen species by neutrophils.
Protective Effect of Nifedipine against Carrageenan-Induced Inflammation
Authors: Sánchez Sílvia , Bartrons Ramon , Rodríguez Leocadio , González Pedro , Planas M. Eulàlia 
Published: April 2003

Administration of carrageenan (CA; 0.5 mg) to the plantar tissue of rats resulted in reversible inflammatory injury. The edema was monitored by changes in paw volume using a plethysmometer. Simultaneous administration of CA and nifedipine, intraperitoneally, at different doses (10, 20 and 50 mg/kg) prevented the inflammatory action, and the effect was dose- and time-dependent. In order to improve the nifedipine effects, we prepared liposomed nifedipine which, administered intraperitoneally, showed a greater anti-inflammatory action. In the presence of the L-type channel agonist Bay K 8644, the inflammation produced by CA increased and it was counteracted by free or liposomed nifedipine. The significance of these findings with respect to the mechanism of the anti-inflammatory action of nifedipine is discussed.
Comparative Analgesic Activity of Nimesulide and Diclofenac by Intramuscular Route: Correlation with Pharmacokinetic Profile of Nimesulide
Authors: Gupta S.K. , Velpandian T. , Mathur P. , Sengupta S. 
Published: April 2003

Nimesulide, a selective cyclooxygenase-2-inhibiting nonsteroidal anti-inflammatory drug, has been found to be a potent anti-inflammatory and analgesic drug, when administered orally, rectally or topically. The aim of the present study was to evaluate the comparative efficacy of intramuscularly injected nimesulide with that of diclofenac and to elucidate the pharmacokinetic profile of this formulation. Swiss albino mice were used in the experiment. Analgesic activity was tested using the acetic acid writhing test and the tail-flick latency test. Plasma levels of nimesulide and its active metabolite, hydroxynimesulide, were determined by a HPLC method. A peak analgesic effect was observed between 60 and 120 min, while C<sub>max</sub> (10.6 ± 3.8 µg/ml) of nimesulide was reached at 60 min (T<sub>max</sub>). Analgesia was induced within 15 min of administration of nimesulide and was significantly higher than that of diclofenac at 90 and 120 min posttreatment in the writhing reflex and at 60 and 90 min in the tail-flick latency test. The results indicate that intramuscularly injected nimesulide may be an alternative mode of administration in uncooperative patients or when immediate analgesic effects are warranted.
Heterogeneity of α<sub>1</sub>-Adrenoceptor Subtypes Mediating Noradrenaline-Induced Contractions of theRat Superior Mesenteric Artery
Authors: Yousif Mariam , Kadavil Elizabeth A. , Oriowo M.A. 
Published: April 2003

The effects of subtype-selective α<sub>1</sub>-adrenoceptor antagonists on noradrenaline-induced contractions of ring segments of rat superior mesenteric artery were investigated to determine the subtype(s) of α<sub>1</sub>-adrenoceptors mediating contractions in this preparation. Noradrenaline-induced contractions of rat mesenteric artery ring segments were potently and surmountably antagonized by prazosin, WB 4101 and BMY 7378. Judging from the slopes of the Schild regression lines, which were significantly different from 1, WB 4101 and BMY 7378 behaved as noncompetitive antagonists. Spiperone and 5-methylurapidil were only effective at high concentrations. Chloroethylclonidine (CEC, 100 µmol/l) displaced the noradrenaline concentration-response curve to the right reducing its potency approximately 100-fold. Noradrenaline-induced contractions post-CEC were also antagonized by prazosin. However, prazosin was less potent against these contractions. A 61603, a selective α<sub>1A</sub>-adrenoceptor agonist, contracted ring segments of the mesenteric artery. These contractions were antagonized by prazosin, however with a low affinity, indicating interaction with a low-affinity receptor subtype. It was therefore concluded that α<sub>1D</sub>- and, possibly, α<sub>1L</sub>-adrenoceptor subtypes mediated noradrenaline- induced contractions of the rat superior mesenteric artery.
Inhibitory Effects of TRK-530 on Rat Adjuvant Arthritis
Authors: Tanahashi Masahiko , Funaba Yuriko , Itoh Masatoshi , Kawabe Norio , Nakadate-Matsushita Teruo 
Published: April 2003

TRK-530 is a novel bisphosphonate derivative. We examined the anti-inflammatory effects of TRK-530 on adjuvant arthritis (AA) rats. When TRK-530 at a dose of 2.5 mg/kg was administered for 2 weeks to AA rats, it inhibited destructive changes in arthritic joints such as paw edema, bone loss and joint degeneration. TRK-530 also inhibited splenomegaly and suppressed the increase in serum sialic acid which is measured as a systemic parameter of inflammation. To clarify the inhibitory mechanism of TRK-530, interleukin-1 (IL-1)-like activities of resident peritoneal macrophages in AA rats given TRK-530 were compared with those of control rats. We found that TRK-530 inhibited IL-1-like activity induced by bacterial lipopolysaccharide 6 weeks after administration when the IL-1-like activities of control rats were still at high levels. These findings suggest that TRK-530 exerts anti-inflammatory activities in AA rats.