bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antitussive Action of Antihistamines Is Independent of Sedative and Ventilation Activity in the Guinea Pig
Authors: McLeod Robbie L. , Mingo Garfield , O’Reilly Sandra , Ruck LoriAnn , Bolser Donald C. , Hey John A. 
Published: April 2003

We studied the oral actions of antihistamines from six chemical classes, namely: the ethanolamines (ENA, diphenhydramine and clemastine); ethylenediamines (EDA, pyrilamine and tripelennamine); piperidines (PPD, terfenadine and astemizole); piperazines (PPZ, hydroxyzine and cetirizine); phenothiazines (PTZ, promethazine), and the alkylamines (ALA, chlorpheniramine and bromopheniramine) on cough reflexes, pentobarbital-induced sedation and minute ventilation in the conscious guinea pig. Antihistamines of the ENA class had minimal effects on capsaicin-induced cough although both diphenhydramine (30 and 100 mg/kg p.o.) and clemastine (30 and 100 mg/kg p.o.) increased sedation time (ST). The PPZ class demonstrated both antitussive and sedating activity. The minimum effective oral antitussive dose (MED) of cetirizine and hydroxyzine was 30 and 10 mg/kg, respectively. The EDA did not exhibit antitussive activity. Tripelennamine (10, 30 and 100 mg/kg p.o.) but not pyrilamine enhanced ST. The MED for the PTZ, promethazine, was 10 mg/kg, and at 100 mg/kg promethazine increased ST. The ALA group displayed antitussive activity but only chlorpheniramine (10 mg/kg p.o.) had any effects on ST. The MED for chlorpheniramine and bromopheniramine was 3 and 10 mg/kg p.o., respectively. The PPD antihistamines, namely terfenadine and astemizole, inhibited cough (MED 30 and 10 mg/kg p.o.) without sedative effects. Of the antihistamines tested only promethazine (100 mg/kg p.o.) depressed ventilation responses; however, this dose of promethazine was associated with adverse behavioral effects. The present findings indicate that the antitussive actions of antihistamines are not directly related to histamine H<sub>1</sub>-receptor blockade because several antihistamines did not antagonize capsaicin-induced cough. In addition, the antitussive actions of antihistamines are independent of their sedative or ventilation effects.
Correlation of EGTA and Calcium- Blocking Agents on the Response of the Bladder to in vitro Ischemia
Authors: Levin Robert M. , Leggett Robbert , Whitbeck Catherine , Horan Patrick 
Published: April 2003

The effects of repetitive field stimulation (model of hyperrelexia) on the responses of isolated strips of rabbit urinary bladder to FS and carbachol were evaluated under a variety of incubation conditions. Compared to control conditions, 2 h of repetitive FS in normal, oxygenated Tyrode’s solution followed by incubation for 1 h with no stimulation resulted in a 50% decrease in contractile response to FS and a 30% decrease in the response to carbachol. Incubation in the absence of O<sub>2</sub> and glucose was used as an in vitro model for ischemia. Repetitive stimulation during in vitro ischemia resulted in a significantly greater decrease in the contractile responses to FS and carbachol than did in vitro ischemia without repetitive stimulation. The magnitude of contractile dysfunctions in response to both stimuli were significantly reduced in the presence of EGTA (calcium chelator), diltiazem (calcium channel blocker) or pincidil (potassium channel opener). Incubation with thapsigargin (SR calcium uptake inhibitor) + ryanodine (SR calcium storage inhibitor) had no effect. The results of these studies indicate that inhibition of Ca<sup>2+</sup> entry reduces the contractile dysfunctions induced by repetitive stimulation in the presence of in vitro ischemia. Inhibition of Ca<sup>2+</sup><sub>i</sub> storage and release had no significant effect on the magnitude of contractile dysfunctions induced by repetitive stimulation an in vitro ischemia.
Role of Oxidative Stress and Glutathione in Busulfan Toxicity in Cultured Murine Hepatocytes
Authors: DeLeve Laurie D. , Wang Xiangdong 
Published: April 2003

This study examines busulfan metabolism. Busulfan given in vivo or in vitro decreased hepatocyte glutathione (GSH) by 60 and 50%, respectively. In vitro, busulfan toxicity was prevented by glutathione S-transferase inhibitors or by antioxidants and led to increased production of oxidized GSH and thiobarbituric acid reactive substances. ‘Rescue’ from toxicity by GSH precursors was prevented by N,N-bis(2-chloroethyl)-N-nitrosourea (BCNU). Depletion of GSH exacerbated toxicity. In GSH-depleted hepatocytes, busulfan decreased GSH by 95% and BCNU did not prevent rescue by GSH precursors. Conclusions: (1) In hepatocytes with normal GSH: busulfan toxicity requires GSH conjugation, does not cause profound GSH depletion and is mediated by oxidative stress. We postulate that a GSH conjugate promotes oxidative stress. (2) In GSH-depleted hepatocytes: busulfan profoundly depletes GSH; toxicity is mediated by oxidative stress and is prevented by restoring GSH levels; cell death may be due to unopposed endogenous oxidative stress.
An Electropalatographic and Acoustic Study of Temporal Coarticulation for Catalan Dark/l/ and German Clear/l/
Authors: Recasens D. , Pallarès M.D. , Fontdevila J. 
Published: April 2003

Abstract
Electropalatographic and F2 frequency data in /VlV/ sequences reveal more prominent C-to-V effects for Catalan dark /l/ than for German clear /l/, more so in the /i/ context than in the /a/ context, which is in agreement with the existence of high lingual requirements on the formation of two constriction places for dark /l/. German clear /l/ exerts a similar amount of F2 displacement on both vowels which may be indicative of the tongue dorsum being directed towards a target position; this is also suggested by dorsopalatal contact and formant frequency data showing less vowel-dependent variability than clear /l/ in other languages though more so than Catalan dark /l/. Salient anticipatory requirements for the implementation of /l/ in the two languages block V1-dependent carryover effects to a large extent which results in more prominent vocalic anticipation than vocalic carryover. This directionality trend in vocalic coarticulation is more obvious for Catalan dark /l/ than for German clear /l/ (in agreement with the former consonantal variety requiring more anticipation than the latter) and opposes German /l/ to clear /l/ in other languages (i.e., the less constrained /l/ variety of Spanish may favor vocalic carryover over vocalic anticipation in VCV sequences).
Categorical Perception as a Function of Stimulus Quality
Authors: van Hessen A.J. , Schouten M.E.H. 
Published: April 2003

AbstractA number of experiments were carried out in order to test the hypothesis that categorical perception of speech stimuli is a function of synthetis quality – specifically, that the greater complexity of more natural speech stimuli makes it difficult for listeners to focus on particular stimulis parameters as psychoacoustic cues. The results show that there is an increase in categorical perception as synthesis quality improves from a simple synthesis by rule, via LPC synthesis, to a much more complex type called sinewave generation.
Articulatory Vowel Lengthening and Coordination at Phrasal Junctures
Authors: Byrd Dani 
Published: April 2003

Abstract
Recent work has demonstrated that progressively stronger prosodic boundaries result in increasing amounts of lengthening for consonant gestures, both preceding and following the boundary. The present experiment extends these earlier findings by considering kinematic data collected with a magnetometer to determine (1) if vocalic gestures demonstrate lengthening patterns comparable to those of consonantal gestures due to adjacent prosodic boundaries, and (2) if the relative timing of consonant and vowel gestures is affected by adjacent boundaries. A magnetometer system was used to track articulator movements of 3 speakers producing sentences in which a /...C<sub>1</sub>V<sub>1</sub>(#)C<sub>2</sub>V<sub>2</sub>.../ sequence was embedded with varying medial boundaries. All subjects demonstrated lengthening of the vocalic articulation before stronger boundaries. Additionally, effects on the relative timing of words spanning a boundary and the relative timing of segments in boundary-adjacent syllables were observed.
The Question of ‘Stress’ in West Greenlandic1
Authors: Jacobsen Birgitte 
Published: April 2003

AbstractThe main purpose is to investigate whether stress is a relevant category in Greenlandic word prosody. I focus on tonal and durational parameters. The data material consists of word lists read aloud seven times by two subjects. The main findings are: (1) The prosodic characteristics of words can be explained in either tonal or durational terms. (2) The four different syllable types (of different ‘weight’) are distinguished in durational terms; further, there appears to be only a tripartite system of short, long and overlong. (3) There are intra-syllabic as well as inter-syllabic rhythmical adjustments. It is concluded that Greenlandic prosody does not include an autonomous stress category, either tonal or durational parameters alone will do. And although Greenlandic has distinctive quantity, there is room for considerable durational variation of segments.
Fundamental Frequency Peak Delay in Mandarin
Authors: Xu Yi 
Published: April 2003

Abstract
Fundamental frequency (F₀) peak delay (henceforth peak delay) refers to the phenomenon that an F₀ peak sometimes occurs after the syllable it is associated with either lexically or prosodically. Although peak delay has been reported for various languages, the mechanism of its occurrence has so far remained unclear. In Mandarin, peak delay has been found to occur regularly in the rising (R) tone but not in the high (H) tone. The present study investigates the underlying mechanisms of peak delay by examining its relationship with tone, tonal context, and speech rate. An experiment was conducted to test the possibility that peak delay may occur also in the H tone in Mandarin if the H-carrying syllable is sufficiently shortened. Native speakers of Mandarin Chinese recorded three types of sentences each containing a H, a R, or a weakened H tone. The sentences were produced at three speech rates: normal, fast and slow. Analysis of F₀ contours and peak alignment revealed that at normal speech rate, peak delay occurred regularly in both the R and weakened H tones but only occasionally in the H tone; at slow speech rate, peak delay continued to occur regularly in the R tone but only occasionally in weakened H and rarely in the H tone; at fast speech rate, peak delay occurred not only regularly in the R and weakened H tones, but also frequently in the H tone. Results of F₀ contour alignment analysis indicate that peak delay occurs when there is a sharp F₀ rise near the end of a syllable, regardless of the cause of the rise. The finding of this study provides support for the view that, rather than due to actual misalignment between underlying pitch units and segmental units, much of the variability in the shape and alignment of F₀ contours in Mandarin is attributable to the interaction of underlying pitch targets with tonal contexts and articulatory constraints.
Depression and the Severity of Substance Abuse
Authors: Coelho Rui , Rangel Rui , Ramos Elisabete , Martins Amadeu , Prata Joana , Barros Henrique 
Published: April 2003

<i>Background:</i> Psychosocial factors have been considered important in the initiation of drug abuse and seem to affect its clinical course and outcome. Several studies have reported psychopathology, namely depression, to be consistently high in addiction. The aim of this investigation was to evaluate the prevalence of depression and its relationship to the severity of drug abuse in a Portuguese sample of drug addicts. <i>Methods:</i> Two hundred and eighty-five drug addicts (23 women and 262 men, aged between 16 and 41 years old), diagnosed according to the DSM-IV criteria, were contacted during their first visit for treatment at public health centres. Social, demographic and behavioural characteristics of the study sample were obtained by interview using a structured questionnaire. The severity of drug abuse was evaluated using a Portuguese version of the Drug Abuse Screening Test, and depression was assessed by the Zung self-rating depression scale. <i>Results:</i> The prevalence of depression was 51.2% and was higher in females than males (77.8 vs. 48.7%, p = 0.034). A significant correlation was also found between the severity of drug abuse and depression scores, which was also stronger in females (r = 0.53 vs. r = 0.24). <i>Conclusions:</i> This study showed a high prevalence of depression in drug addicts, regardless of the type and duration of drug abuse, and a significant association between depression and severity of drug addiction.
Water-Soluble Cooling Lubricants Induce Airway Hyper- responsiveness in Rabbits
Authors: Marek W. , Mensing T. , Fricke H. , Baur X. 
Published: April 2003

Airway hyperresponsiveness (AHR) to water-soluble cooling lubricants (CL) induced by aerosol administered by tracheal tube was studied in a rabbit model of occupational lung disease. Two commercial CL were examined: the first was of the boric acid amine ester type without biozide (CL-BAE), the second was of the sulfonate type with biozide (CL-SB). 50, 5.0 or 0.5 mg/m<sup>3</sup> CL was administered over a period of twice 2 h to six different groups of rabbits. Airway responsiveness (AR) to aerosols of 0.2% and 2.0% acetylcholine solution (ACH) was measured before and after each exposure to CL. A control group A of nine animals not exposed to CL showed no significant respiratory responses following inhalation of 0.2% ACH for 1 min. Conversely, inhalation of 2.0% ACH almost doubled the dynamic elastance (E<sub>dyn</sub>) in the ACH challenge test in this animal group. Airway resistance (R<sub>I</sub>), E<sub>dyn</sub>, slope of inspiratory pressure generation (ΔP<sub>es</sub>/t<sub>I</sub>), arterial pressure (P<sub>a</sub>) and arterial blood gas tensions (P<sub>a</sub>O<sub>2</sub>, P<sub>a</sub>CO<sub>2</sub>) were not significantly altered during and after exposures to CL. However, after CL-BAE inhalation of 50 and 5 mg/m<sup>3</sup> over 4 h, the amplitude of the ACH-induced airway obstruction indicated by the changes in E<sub>dyn</sub> rose significantly to almost five times the control response before exposure (group C, D, p < 0.005). Similar changes in R<sub>I</sub> and ΔP<sub>es</sub>/t<sub>I</sub> were obtained. After inhalation of 0.5 mg/m<sup>3</sup> CL-BAE (group D), no significant changes in AR were observed. Similar to CL-BAE inhalation of 50 mg/m<sup>3</sup>, CL-SB caused enlarged AR in the ACH challenge test (group E), whereas no significant changes were found after exposure to 5.0 and 0.5 mg/m<sup>3</sup> in groups F and G. In summary, CL aerosols with and without biozide in the range of 50 and 5 mg/m<sup>3</sup> applied via tracheal tubes increased AR to ACH within 4 h of exposure in a time- and concentration-dependent manner. It has to be assumed that this augmented AR indicates an increased risk of developing lubricant-induced obstructive lung diseases.
Acute Lung Injury after Inhalation of Water-Proofing Spray while Smoking a Cigarette
Authors: Jinn Yasuto , Akizuki Norikazu , Ohkouchi Minoru , Inase Naohiko , Ichioka Masahiko , Marumo Fumiaki 
Published: April 2003

A 34-year-old Japanese woman developed acute lung injury soon after inhaling a water-proofing spray which she applied onto her ski suit while smoking a cigarette at the same time. She initially demonstrated arterial hypoxemia (PaO<sub>2</sub> = 59 mm Hg) and ground-glass opacities in both lung fields on the CT scan, which both returned to normal without any medication. Several water-proofing sprays, which are easily obtainable in Japan, contain 1,1,1-trichloroethane, liquefied petroleum gas and fluoride resin. Although these components have not been reported to be toxic to the lung yet, high concentrations of these components and/or the pyrolytic products of fluoride resin may have caused acute lung injury in this case.
An Unusual Case of Esophageal Tuberculosis in an Adult
Authors: Alataş Füsun , Özdemir Necla , Işıksoy Serap , Metintaş Muzaffer , Erginel Sinan , Harmancı Emel , Mutlu Sevda 
Published: April 2003

Tuberculous infection of the esophagus is a rare disease and usually occurs secondary to tuberculous mediastinal lymphadenopathy. We report a 74-year-old woman presenting with dysphagia and weight loss. The chest radiograph showed punctuated calcifications lining from the right hilar region to the paracardiac region. Upper gastrointestinal endoscopy revealed a 0.5 × 5 cm lesion localized in the 25th cm of the esophagus covered partly with normal mucosa, partly demonstrating ulcerous areas. Biopsy revealed granulomatous infiltrates being tuberculoid in type. Thorax CT showed a calcified lymph node at the right hilum. The patient did not give consent to therapy and died 1 month later.
Percutaneous Absorption of Methylprednisolone Aceponate following Topical Application of Advantan<sup>®</sup> Lotion on Intact, Inflamed and Stripped Skin of Male Volunteers
Authors: Günther C. , Kecskes A. , Staks T. , Täuber U. 
Published: April 2003

Six healthy, elderly volunteers received three topical treatments with Advantan<sup>®</sup> lotion containing 0.1% of methylprednisolone aceponate (MPA, CAS 86401-95-8) on intact, inflamed and stripped skin in a consecutive fashion at weekly intervals. The lotion (O/W emulsion) containing <sup>14</sup>C-MPA (specific radioactivity 1.8 MBq/mg MPA) was applied in an area dose of 5 mg lotion/cm<sup>2</sup> on a marked area of 100 cm<sup>2</sup> on the back for 24 h. Inflammation was caused by UV-B irradiation at 3 MED 6 h prior to the treatment with the test preparation. Removal of stratum corneum was performed by 20-fold adhesive tape stripping. The concentration of radioactivity was measured in the plasma and in the urine up to 7 days following each treatment. The concentration of radioactivity in the plasma did not exceed the limit of detection of 1.5 ng MPA Eq/ml at any time point. The percutaneous absorption was assessed from the cumulated excretion of radiolabelled substances in the urine corrected for biliary excretion. Less than 0.5% of the dose was percutaneously absorbed through intact skin and through inflamed skin. After removal of the penetration barrier (‘stripping’) the percutaneous absorption increased to 15.4±7.7% of the applied dose.
Ethanol-Modulated Cytokine Production and Expression in Skin Cells Exposed to Methotrexate
Authors: Shear Neil H. , Landau Marina , Malkiewicz Izabella , Katz Gady G. , Neuman Manuela G. 
Published: April 2003

Evidence suggests a link between alcohol consumption, psoriasis and the response of psoriatic patients to methotrexate (MTX) therapy. Ethanol (EtOH) may play a role in the pathogenesis of psoriasis by upregulating the expression and inducing the local secretion of proinflammatory cytokines, e.g. interleukins IL-1α, IL-6, chemokine IL-8 and tumor necrosis factor alpha (TNF-α). We investigated whether EtOH or MTX or their combination influence the secretion of these cytokines using normal human primary skin cells (NHPSC) and epidermoid cell line A431. The objectives of this study were: (1) to quantify the differences in cellular changes induced by MTX, (2) to measure the effect of EtOH on MTX toxicity and (3) to determine the relationship between MTX and EtOH exposure and production of proinflammatory cytokines. NHPSC and A431 were incubated with 0–10 m<i>M</i> MTX or α-MEM (control) in the presence or absence of 40 m<i>M</i> EtOH. A formazan 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used as a marker for cell viability (control was 100%). Significance was calculated by ANOVA. Cytokine release into media was quantitated by ELISA. After 24 h of MTX exposure, the release of IL-1α was unchanged. IL-6 increased 1.7 times in both cultures, and IL-8 increased 1.7 times in NHPSC and 2.1 times in A431. TNF-α release increased twice in A431 but not in NHPSC. Human recombinant IL-1α and IL-6 for 24 h had no effect, while TNF-α reduced cytoviability by 30% in NHPSC and 22% in A431. Anti-TNF-α reversed the effect produced by TNF-α in NHPSC and reduced it in A431 (11.8%, p < 0.05). We concluded that in vitro in normal human primary keratinocytes, toxicity and inflammatory responses are enhanced by EtOH.
Pharmacological Effects of a Specific Leukotriene B<sub>4</sub> Receptor Antagonist (VML 295) on Blood Leukocytes, Cutaneous Inflammation and Epidermal Proliferation
Authors: Seegers Bianca A.M.P.A. , Andriessen Monique P.M. , van Hooijdonk Candida A.E.M. , de Bakker Els S.M. , van Vlijmen-Willems Ivonne M.J.J. , Parker Gerry L. , van Erp Piet E.J. , van de Kerkhof Peter C.M. 
Published: April 2003

VML 295 (LY 293111) is a potent and specific leukotriene<sub>4</sub> receptor antagonist. It has previously been shown in human volunteers that VML 295 at a dosage of 48 mg twice daily inhibits the ex vivo leukotriene B<sub>4</sub> (LTB<sub>4</sub>)-induced upregulation of CD11b on peripheral blood neutrophils. A clear dose-response relatinship was shown. In addition, VML 295 inhibits various inflammatory aspects resulting from LTB<sub>4</sub> challenge of the skin, again showing a dose-response relationship. In view of the large variation in the elimination half-life of VML 295 (25–88.5 h) in individual human subjects, the present pharmacological study was designed to provide information on the pharmacodynamics of the drug by the assessment of VML 295 plasma concentrations, ex vivo LTB<sub>4</sub>-induced CD11b upregulation of neutrophils, neutrophil accumulation in the skin following epicutaneous application of LTB<sub>4</sub> and epidermal regeneration following standardized surface trauma. A group of 36 healthy volunteers were treated in a double-blind study with VML 295 at 200 mg twice daily, VML 295 at 200 mg once daily or placebo for 7 days. Before treatment, at the end of treatment and following discontinuation of treatment, VML 295 plasma concentrations and CD11b upregulation of blood neutrophils were assessed. In 18 subjects, the effects of the three treatments on LTB<sub>4</sub>-induced inflammatory were assessed before and at the end of treatment, and in the remaining 18 subjects the effects of these treatments on epidermal regeneration were assessed similarly. VML 295 at 200 mg either twice or once daily has a profound inhibitory effect on ex vivo LTB<sub>4</sub>-induced CD11b upregulation of blood neutrophils, LTB<sub>4</sub>-induced neutrophil accumulation in the skin, trauma-induced hyperproliferation of the epidermis and regenerative keratinization. The twice daily dose schedule was significantly more effective than the once daily regimen in reducing ex vivo CD11b stimulation of neutrophils, in blood samples collected 24 h after discontinuation of VML 295 treatment. The twice daily schedule tended to be more efficient in skin biopsies, although this difference was not statistically significant in the number of subjects investigated. A plasma concentration of 100 ng/ml proved to be the threshold for these effects. The profound biological effects, both systemically and cutaneously, as well as the safety profile, make VML 295 a promising drug for skin disorders characterized by epidermal proliferation and neutrophil accumulation.