bluuebunny/crossref_metadata_2025 huggingface dataset:
Two‐ to three‐fold increase in blood tacrolimus (FK506) levels during diarrhea in liver‐transplanted children
Authors: Berengue Juan Iglesias , López‐Espinosa Jesús Alberto , Ortega‐López Juan , Sánchez‐Sánchez Luz , Castilla‐Valdes Patricia , Asensio‐Llorente Marino , Margarit‐Creixell Carlos
Published: May 2003

Abstract: Background: The diagnosis and treatment of diarrhea in liver transplant recipients often pose a challenge owing to the variety of infectious and non‐infectious causes. However, diagnosis is principally focused on ruling out an infectious etiology. Tacrolimus, an immunosuppressive agent generally used after liver transplantation, is absorbed mainly from the duodenum through the upper jejunum. It can be assumed that metabolism of the drug will be influenced by diarrhea.

Methods: Four liver transplant recipients who developed an episode of acute gastroenteritis. Infectious etiology was confirmed; trough tacrolimus levels were measured before, during and after gastroenteritis.

Results: All patients presented a two‐ to three‐fold increase in blood tacrolimus levels after the onset of gastroenteritis.

Conclusions: Until the role played by the intestine in the metabolism of tacrolimus is fully understood, it is prudent to recommend early dose reduction of tacrolimus and careful monitoring of trough levels during diarrheal disorders of any nature in pediatric liver‐transplanted patients.
The dynamics of antidonor antibody formation early after clinical kidney transplantation measured by flow cytometry and microcytotoxicity test
Authors: Groth Jürgen , Kaden Jürgen , May Gottfried , Schönemann Constanze
Published: May 2003

Abstract:  To study the dynamics of antidonor sensitization 92 patients were monitored for antibodies against donor T and B spleen lymphocytes before transplantation, within the first month after transplantation and 3 months after transplantation. Patients were monitored for donorreactive antibodies (DRA) of immunoglobulin G (IgG), IgA, and IgM isotype using flow cytometry (FC) and the standard microcytotoxicity test (CYT). Graft function was followed for at least 2 yrs, 51% of patients for 3 yrs after transplantation. Within the first month after transplantation the percentage of patients with antidonor sensitization detected by FC rose dramatically, so that the overall sensitization rate increased from 28 (30.4%) of 92 patients prior to transplantation to 63 (68.5%) of 92 patients after transplantation. Whereas preoperatively only one isotype (IgM for T lymphocytes, IgG for B lymphocytes) and only one target cell type (either T or B lymphocytes) dominated, the postoperative patterns of positive FC results were more variable regarding target and isotype, whereby FC‐DRA of the IgA class substantially contributed. Appearance of donor‐directed antibodies early after kidney transplantation is a frequent event. In our cases, sensitization with FC‐DRA per se seemed not to be detrimental to the graft outcome (p > 0.05) but CYT‐DRA did resulting in a significant poor graft outcome 3 months after transplantation (p < 0.001).
Recurrent allograft HCV presenting as acute cellular rejection: successful management with interferon and ribavirin alone
Authors: Leung Jessica Y , Abraczinskas Diane R. , Bhan Atul K , Terella Adam M , Pascual Manuel , Cosimi A Benedict , Chung Raymond T
Published: May 2003

Abstract:  Hepatitis C virus (HCV) is currently the leading indication worldwide for orthotopic liver transplantation. However, the majority of patients receiving transplant for HCV eventually develop histopathologic evidence of recurrent allograft HCV and approximately 10% die or require retransplantation within the first 5 post‐operative years because of accelerated graft injury and cirrhosis. Traditional induction immunosuppressive regimens and intensive immunosuppression used to treat episodes of acute cellular rejection (ACR) are associated with enhanced viral replication and higher likelihood and severity of recurrent HCV. At our institution, therefore, we have used low‐dose steroid therapy in an effort to limit HCV replication. However, this practice has been associated with frequent early presentations consistent with ACR. Here, we present three cases consistent with histologic ACR treated with conventional antirejection therapy that improved transiently, but evolved rapidly to progressive HCV. A fourth patient with a similar presentation experienced dramatic improvement in aminotransferases when treated solely with interferon and ribavirin. We propose that histologic characteristics traditionally associated with ACR may, in fact, represent early recurrent HCV as both processes share common immunopathogenetic mechanisms, or alternatively, that both ACR and recurrent HCV may be present simultaneously. We conclude that in cases suggestive of ACR, careful consideration should be given to treatment for recurrent HCV in lieu of or in concert with intensive immunosuppression.
A comparative kinetic study on the singlet molecular oxygen‐mediated photoxidation of α‐ and β‐chymotrypsins
Authors: Biasutti M.A. , Posadaz A. , García N.A.
Published: May 2003

Abstract: Kinetic aspects of the sensitized photooxidation of α‐ and β‐chymotrypsins have been studied at pH 6 and 8. The sensitization, employing classical O2(1Δg)‐photogenerators, such as xanthene dyes, is a kinetically intricate process because of the presence of ground state dye–protein associations and to the simultaneous participation of superoxide ion and singlet molecular oxygen [O2(1Δg)].

Both proteins, that possess the same distribution pattern of photooxidizable amino acids, suffer a pure O2(1Δg)‐mediated photodynamic attack, using the carbonylic sensitizer Perinaphthenone. Overall and reactive rate constants for the O2(1Δg)‐quenching (in the order of 108 and 107/M/s, respectively), and rates of oxygen consumption determined by time‐resolved, spectroscopic and polarographic methods indicate that α‐ and β‐chymotrypsins are less photooxidizable at pH 6, as a result of an enhancement of the O2(1Δg)‐physical quenching component. In general terms, β‐chymotrypsin exhibits the greater overall proclivity to interact with O2(1Δg), whereas structural factors, possibly evidenced by a higher exposure of the reactive tryptophan residues, impart an increased photooxidation degree to the proteins at pH 8, specially to the α‐chymotrypsin.
The biological consequences of replacing hydrophobic amino acids in deltorphin I with amphiphilic α‐hydroxymethylamino acids
Authors: Olma A. , Łachwa M. , Lipkowski A.W.
Published: May 2003

Abstract: New analogues of deltorphin I (DT I), in which the Phe residue in position 3, and the Val residue in position 5 or 6 are replaced with respective amphiphilic α‐hydroxymethylamino acid residues (HmAA), were synthesized and tested for receptor affinity and selectivity to μ and δ opioid receptors. The analogue with (R)‐HmPhe at position 3 lost receptor selectivity, as a result of a partial decrease of affinity to δ and a significant increase of affinity to μ receptors. In contrast, an analogue with (S)‐HmPhe in the same position, was very potent and more specific to δ receptors than parent DT I. The analogue with (R)‐HmVal at position 5 expressed higher δ affinity and selectivity than parent DT I. The analogue with other possible isomer (S)‐HmVal was less selective for δ opioid receptors, as a result of decreasing affinity to δ and increasing affinity to μ receptors. The analogues with (R)‐ or (S)‐HmVal in position 6 expressed equally low receptor affinity and selectivity. The data obtained support a previously proposed model of active conformation of deltorphins.
Valproate
Authors: Bowden Charles L
Published: May 2003

Objectives: This article summarizes the role of valproate as a treatment for bipolar disorder and related conditions.

Methods: Published studies and reviews were systematically reviewed. Results from randomized, parallel group, double‐blind, placebo‐controlled studies that included an active comparator are emphasized.

Results: Valproate is an effective treatment for manic patients. Valproate was superior to placebo in one 1‐year randomized, parallel group study in rate of recurrence requiring discontinuation, rate of depression requiring discontinuation, total early termination and time to 25% of patients relapsing with mania, and in controlling mild depressive symptoms. On some measures, including time to development of a manic episode, valproate did not differ from placebo. Assessments of maintenance efficacy of valproate and other putative prophylactic treatments for bipolar disorder are problematic, because of the need to analyze multiple indices of efficacy, and practical and ethical issues that limit generalizability of results of placebo‐controlled studies. Valproate has some advantages over lithium in treatment of mania for persons with more severe illnesses. Valproate benefits a broader spectrum of bipolar conditions than lithium. Valproate appears at best modestly effective for bipolar depression. Used in combination with several other treatments, additive benefits result, that are greater than with any of the treatments as monotherapy. Side effects are generally mild and manageable, particularly with divalproex. Weight gain and pharmacokinetic interaction with lamotrigine are perhaps the most consistent problems in use. Valproate contributes to neural tube defects if taken during the first trimester of pregnancy, and this risk must be conveyed to women.

Conclusions: Valproate is an effective and useful treatment for bipolar disorder. Studies clarifying its spectrum of efficacy, its safety and efficacy in combination regimens, and its mechanisms of action are warranted.
Recent concepts in plaque formation
Authors: Bernimoulin J.‐P.
Published: May 2003

Dental plaque is an adherent, bacterial film, and is the main pathological agent for periodontal diseases. The formation of dental plaque can occur both supragingivally and subgingivally. The development of plaque is a three‐step process. Following the formation of a pellicle, pioneer micro‐organisms will adhere to it, proliferate and form colonies. The final stage involves the aggregation of filamentous organisms and spirochetes into a cohesive biofilm. Many products of the plaque bacteria reach the subepithelial tissue, causing inflammatory responses such as increased vascularity and leukocyte diapedesis. Both supragingival and subgingival plaque may form a hard, mineralized mass called calculus. The surface of calculus harbours bacteria, which may exacerbate the inflammatory responses. An effective oral antiseptic must be active against a wide range of Gram‐positive and Gram‐negative bacterial species, including streptococci and fusobacteria. Ideally, an effective agent would also penetrate the plaque biofilm. Data show that essential oil and chlorhexidine mouthwashes have the broadest antimicrobial effects.
Evidence‐based control of plaque and gingivitis
Authors: Santos A.
Published: May 2003

Most adults brush and floss inadequately, and constant education and/or reinforcement is often required. Bacteria are usually left behind with mechanical oral health routines, and chemotherapeutic agents may have a key role as adjuncts to daily home‐care. To date, two antiseptic mouthwashes have received the ADA Seal of Acceptance: Peridex® (Zila Pharmaceuticals, Phoenix, AZ, USA; CHX, chlorhexidine) and Listerine® (Pfizer Consumer Healthcare, Morris Plains, NJ, USA; essential oil (EO) mouthwash). CHX has a strong affinity for tooth and tissue surfaces, but can cause brown staining on the teeth and tongue. Patients must also wait until all traces of toothpaste are removed before rinsing with CHX. Long‐term use of an EO mouthwash is microbiologically safe, with no changes observed in the bacterial composition of supragingival plaque, and no evidence of antimicrobial resistance. A number of trials have demonstrated the long‐term plaque‐ and gingivitis‐reducing properties of both CHX and EO mouthwashes. These studies clearly demonstrate that these agents have lasting efficacy, and can access hard‐to‐reach areas.
Additional properties and uses of essential oils
Authors: Seymour R.
Published: May 2003

Much evidence has been published supporting the use of mouthwashes in a number of crucial areas of oral health. These areas include antibacterial activity, home irrigation, maintenance of implant health, postsurgery uses, reduction of bacteria in dental aerosols and bacteraemia reduction. Although other commonly used mouthwashes (e.g. chlorhexidine) have been reviewed in other articles in this Supplement, this article concentrates solely on data supporting essential‐oil mouthwash use in these oral health areas.
Essential oil mouthwashes: a key component in oral health management
Authors: Claffey N.
Published: May 2003

This Supplement provides clear evidence that essential oil (EO) mouthwashes can be a beneficial, safe component of daily oral health routines. However, despite the wealth of supporting evidence, several issues are worthy of discussion. Patient compliance is a clear issue with oral home‐care routines, and the emphasis is on dental professionals to communicate the importance of adherence. The reasons for each step of the oral‐care routine (i.e. brushing, flossing, rinsing) should be clearly explained, and if required, additional motivation should be provided. Most mouthwashes contain denatured alcohol as a delivery vehicle, and some concern has been raised about the association of alcohol with oral cancer. However, a review by the Food and Drug Administration and American Dental Association found that the supporting evidence to date is inconsistent and contradictory. Some mouthwashes have a pH below 5.5, and some researchers believe that this can lead to tooth erosion. Studies have shown that although the pH of an EO mouthwash is below 5.5, salivary pH remains above 5.5 following rinsing and for 15 min postrinse.
The role of 3‐dimethylaminopropylamine and amidoamine in contact allergy to cocamidopropylbetaine
Authors: Foti Caterina , Bonamonte Domenico , Mascolo Giuseppe , Corcelli Angela , Lobasso Simona , Rigano Luigi , Angelini Gianni
Published: May 2003

Since it has been found that all subjects with contact allergy to cocamidopropylbetaine (CAPB) have positive reactions to 3‐dimethylaminopropylamine (DMAPA), and reports have appeared in literature of the sensitizing action of amidoamine in products containing CAPB, we aimed to verify the possibility that pure amidoamine may have a sensitizing role in subjects with positive reactions to CAPB. To this end, in 10 patients with contact allergy to a commercial CAPB, we tested DMAPA 1% aq. and a pure amidoamine in concentrations ranging from 0·5% aq. to 0·1% aq. The study showed that all patients with positive reactions to DMAPA reacted to amidoamine at 0·5% and 0·25% aq., while 4 of the 10 also had positive reactions to amidoamine at 0·1% aq. We consider that simultaneous allergic reaction to DMAPA and amidoamine represents cross‐reactivity and hypothesize that DMAPA is in fact the true sensitizing substance, while amidoamine, which may in any case release DMAPA in vivo as a result of enzymatic hydrolysis, may favour the transepidermal penetration of the sensitizing agent. In addition, we advise that testing of CAPB be suspended, because, as suggested by chemico‐structural analyses and demonstrated in vivo, when thoroughly purified, it no longer has a sensitizing action.
Deodorants: an experimental provocation study with hydroxycitronellal
Authors: Svedman C. , Bruze M. , Johansen J. D. , Andersen K. E. , Goossens A. , Frosch P. J. , Lepoittevin J.‐P. , Rastogi S. , White I. R. , Menné T.
Published: May 2003

Axillary dermatitis is a common problem, particularly in individuals with contact allergy to fragrances. Many individuals suspect their deodorant to be the causal product of their fragrance allergy. It has been shown that deodorants containing cinnamic aldehyde (cinnamal) can elicit axillary dermatitis in patients sensitized to this substance. The aim of the present investigation was to evaluate the importance of hydroxycitronellal used in deodorants for the development of axillary dermatitis, when applied by individuals with and without contact allergy to this fragrance chemical. Patch tests with deodorants and ethanolic solutions containing hydroxycitronellal, as well as repeated open application tests (ROAT) with roll‐on deodorants with and without hydroxycitronellal at different concentrations, were performed in 14 dermatitis patients, 7 with and 7 without contact allergy to hydroxycitronellal. A positive ROAT was noted only in the patients hypersensitive to hydroxycitronellal (P < 0·001) and only in the axilla to which the deodorants containing hydroxycitronellal had been applied (P < 0·001). Deodorants containing hydroxycitronellal in the concentration range of 0·032–0·32% used twice daily on healthy skin in individuals hypersensitive to hydroxycitronellal can elicit axillary dermatitis in a few weeks.
Student Power – Holberg's Ideas on Education
Authors: Bredsdorff Thomas
Published: May 2003

Ludvig Holberg (1684–1754) is the most prominent Scandinavian proponent of the ideas of the Enlightenment. A prolific writer in many genres throughout his life he was a great adaptor and compiler rather than an original thinker, except for two fields: gender and education. The paper deals with the latter, notably his ideas on adult education.

A childless bachelor, he had little to say about the rearing of children. He obtained his experience with young adults from his professional duties as a professor at the University of Copenhagen. Academics, now and then, tend to deduce their ideas of how to learn from their ideals of how to teach. Holberg's reasoning was quite the opposite. He held convictions about learning from which he drew conclusions concerning teaching. The resulting ideas were quite advanced in view of the backward and authoritarian institution he served.
Diderot et l'art –éducateur de la société
Authors: Bukdahl Else Marie
Published: May 2003

Denis Diderot est, sans conteste, le plus radical et le plus audacieux des philosophes des Lumières. Libre de tout préjugé, il ne cessa d'apporter, avec une énergie étonnante, ses idées personnelles à tous les nouveaux points de vue de son temps dans les sciences naturelles, la philosophie, l'esthétique et l'art.

Son œuvre est dominée par une démarche unificatrice qui ne s'enferme jamais dans une unité clairement exprimée. Il chercha toujours à créer un lien et une unité dans sa vision du monde, mais il se heurtait sans cesse à de nouveaux aspects et à des phénomènes inexplicables, instables, en perpétuelle évolution. En même temps il s'acharnait à trouver des solutions aux problèmes posés par l'émergence d'une nouvelle société, démocratique et plus humaine. Mais là aussi, il se heurtait à des expériences nouvelles et à des aspects qui transformaient ses conceptions. Il ne trouva jamais une solution qui le satisfasse complètement.
Sakramentaler Expressionismus? Zwei unveröffentlichte Briefe Georg Kaisers an Gustav Landauer
Authors: Krause Frank
Published: May 2003

Während Georg Kaiser in den zivilisations‐ und kulturkritischen Stücken seiner expressionistischen Produktionsphase jeden Versuch einer Ausrichtung der Praxis an metaphysischem Sinn grundlegend problematisiert, hält er in seinen Programmschriften an einem messianischen Verständnis von Literatur als Medium eines sakramentalen Aktes fest. Zwar lassen sich Kaisers programmatische Texte als Versuche interpretieren, mithilfe religiöser Deutungen die Legitimationsprobleme seiner widersprüchlichen Dramatik zu lösen; diese Interpretation setzt sich jedoch dem Einwand aus, Kaiser habe die messianische Programmatik den skeptischen Perspektiven seiner Stücke erst nachträglich aufgesetzt. Zwei bislang unveröffentlichte Briefe Kaisers an Landauer ermöglichen demgegenüber den Nachweis, daß Kaiser die zentralen Thesen dieser Programmatik bereits zur Zeit der Arbeit an seinen expressionistischen Stücken ab 1917 in Anspruch nimmt. Dieser Befund ist nicht nur für die Spezialforschung interessant, die Landauers Beitrag zu Kaisers mystischem Literaturverständnis bislang vernachlässigt hat. Als einer der zentralen Dramatiker des Expressionismus wäre Kaiser auch für die aktuelle Epochenforschung von Interesse, die das Verhältnis der literarischen Moderne zur Sakralisierung der Literatur uneinheitlich bewertet.
Use of antimicrobial agents during supportive periodontal therapy
Authors: Venezia E , Shapira L
Published: May 2003

Individual susceptibility to periodontal breakdown involves an interplay of genes, periodontal pathogens and other modulating factors. Anti‐infective treatment, which includes oral hygiene measures, mechanical debridement, pharmacologic intervention and surgery, has been shown to be effective in arresting the progression of periodontal disease. Nevertheless, due to the chronic nature of the disease, susceptible individuals who are not maintained in a supervised recall program subsequent to the active treatment phase, show signs of recurrent destruction. Supportive periodontal therapy (SPT) is an integral part of periodontal treatment for patients with history of periodontitis, and is needed to prevent recurrence of disease in susceptible individuals. To prevent re‐infection with periodontal pathogens, SPT includes elimination of dental plaque and bacteria from the oral cavity, thereby preventing the recurrence of pathogens into the gingival area. For individuals at risk of developing periodontitis, SPT should combine self‐performed and professional anti‐infective therapy, using mechanical and pharmacological means. The existing evidence suggests that the adjunctive use of antimicrobial pharmacologic therapy during SPT may enhance the results of mechanical debridement. The use of antimicrobials varies between patients, and is dependent on risk assessment and longitudinal monitoring of the clinical status of the periodontium.
Antimicrobials for the treatment of aggressive periodontitis
Authors: Dörfer CE
Published: May 2003

Aggressive periodontitis is characterized by a considerable attachment loss over a relatively short period of time. It may be the consequence of either the presence of highly aggressive pathogens or a highly susceptible host. In the first case, the use of antimicrobials should be beneficial in the treatment of those patients. However, due to the organization of the micro‐organisms as a biofilm, the increasing incidence of allergies and resistance against antimicrobials and their side‐effects, there is still controversy about their benefit in the treatment of periodontal disease. This paper discusses indications for the use of antimicrobials, the substances prescribed and the type of application under the conditions of aggressive periodontitis.
Deviance Regulation: A Theory of Action and Identity
Authors: Blanton Hart , Christie Charlene
Published: May 2003

The authors propose a behavioral decision theory relevant to the maintenance of desirable identities. The theory, termed deviance regulation theory (DRT), predicts that actions translate into meaningful identities to the extent that they cause the individual to deviate from reference group norms. This straightforward proposition is used to predict the patterning of behavior across a wide array of social contexts. The authors present evidence that predictions generalize across Eastern and Western cultures and to both personal and collective identities. Finally, they show how DRT alters current theoretical assumptions about social motives and social and cultural influence, and they illustrate how it can help explain the structure of both informal and formal social forces.
Military Conflict and Terrorism: General Psychology Informs International Relations
Authors: Bourne Lyle E. , Healy Alice F. , Beer Francis A.
Published: May 2003

Several experiments, focusing on decisions made by young, voting-age citizens of the United States about how to respond to incidents of international conflict, are summarized. Participants recommended measured reactions to an initial attack. Repeated attacks led to escalated reaction, however, eventually matching or exceeding the conflict level of the attack itself. If a peace treaty between contending nations was in place, women were more forgiving of an attack, and men were more aggressive. There was little overall difference in reactions to terrorist versus military attacks. Participants responded with a higher level of conflict to terrorist attacks on military than on cultural-educational targets.
Life is Pleasant—and Memory Helps to Keep it that Way!
Authors: Walker W. Richard , Skowronski John J. , Thompson Charles P.
Published: May 2003

People's recollections of the past are often positively biased. This bias has 2 causes. The 1st cause lies in people's perceptions of events. The authors review the results of several studies and present several new comparative analyses of these studies, all of which indicate that people perceive events in their lives to more often be pleasant than unpleasant. A 2nd cause is the fading affect bias: The affect associated with unpleasant events fades faster than the affect associated with pleasant events. The authors review the results of several studies documenting this bias and present evidence indicating that dysphoria (mild depression) disrupts such bias. Taken together, this evidence suggests that autobiographical memory represents an important exception to the theoretical claim that bad is stronger than good.
A rapid nonradioactive peptide phosphorylation assay
Authors: Zeller Martin , Essmann Frank , Jänicke Reiner U. , Schulze‐Osthoff Klaus , König Simone
Published: May 2003

Radioactive assays are commonly employed to monitor protein or peptide phosphorylation. They not only have all the disadvantages related to radioactivity, but also require large amounts of sample. An alternative is the use of mass spectrometric peptide mapping with sensitivities in the fmole range. We demonstrate here that desalting is a requirement for reproducible results, and we optimized the method for very hydrophilic peptide substrates. The method is very efficient with respect to time and effort.
Effects of combined in vivo treatment of transplantable solid mammary carcinoma in Wistar rats using vitamin E and cysteine peptidase inhibitors from human placenta
Authors: Saleh Yousif , Siewiñski Maciej , Sebzda Tadeusz , Grybos Marian , Pawelec Malgorzata , Janocha Anna
Published: May 2003

Cysteine cathepsin B and its endogenous inhibitor play an important role in tumor progression. Increase in cathepsin B expression and reduced levels of its inhibitors were associated with tumor malignancy in breast cancer. The objective of this study was to investigate the effects of a new therapy combining vitamin E and placental inhibitor on the level of endogenous protease inhibitor in sera and tumor tissues with mammary cancer. The inhibitor was used in doses of 100 and 200 μg per animal for 8 days. Vitamin E was added after the last treatment with inhibitor and was injected daily in doses of 10 and 20 mg per animal for one mouth. The size and survival time of treated animals as well as cathepsin B and the inhibitor activity in tumor and sera before and after treatment in comparison with the control groups were determined. The activity of cathepsin B significantly decreased both in tumor tissues and in sera (P ≤ 0.0001). Cathepsin B activity in tumor tissue homogenates and in sera decreased two‐fold and three‐fold, respectively, after the animals were treated with vitamin E at a dose of 20 mg, and decreased five‐fold and 15‐fold, respectively, when treated with vitamin E plus inhibitor in comparison with untreated animals. Endogenous inhibitor activity increased six‐fold and 12‐fold in the sera and tissue homogenates, respectively, after the animals were treated with 200 μg of cysteine protease inhibitor plus 20 mg of vitamin E, in comparison with untreated animals. The total cure responses were higher in eight of 10 rats, as compared with untreated animals. The combination of placental inhibitor and vitamin E resulted in a significant reduction in breast metastasis and might provide a therapeutic basis for anti‐metastasis therapy.
Epidermal growth factor and insulin short‐term increase hPepT1‐mediated glycylsarcosine uptake in Caco‐2 cells
Authors: Nielsen C. U. , Amstrup J. , Nielsen R. , Steffansen B. , Frokjaer S. , Brodin B.
Published: May 2003

Aims: Little is known about the physiological regulation of the human intestinal di/tri‐peptide transporter, hPepT1. In the present study we evaluated the effects of epidermal growth factor (EGF) and insulin on hPepT1‐mediated dipeptide uptake in the intestinal cell line Caco‐2.

Methods: Caco‐2 cells were grown on filters for 23–27 days. Apical dipeptide uptake was measured using [14C]glycylsarcosine([14C]Gly‐Sar). HPepT1 mRNA levels were investigated using RT‐PCR, cytosolic pH was determined using the pH‐sensitive fluorescent probe BCECF.

Results: Basolateral application of EGF increased [14C]Gly‐Sar uptake with an ED50 value of 0.77 ± 0.25 ng mL−1 (n = 3−6) and a maximal stimulation of 33 ± 2% (n = 3−6). Insulin stimulated [14C]Gly‐Sar uptake with an ED50 value of 3.5 ± 2.0 ng mL−1 (n = 3−6) and a maximal stimulation of approximately 18% (n = 3−6). Gly‐Sar uptake followed simple Michaelis‐Menten kinetics. Km in control cells was 0.98 ± 0.11 mM (n = 8) and Vmax was 1.86 ± 0.07 nmol cm−2 min−1 (n = 8). In monolayers treated with 200 ng mL−1 of EGF, Km was 1.11 ± 0.05 mM (n = 5) and Vmax was 2.79 ± 0.05 nmol cm−2 min−1 (n = 5). In monolayers treated with 50 ng mL−1 insulin, Km was 1.03 ± 0.08 mM and Vmax was 2.19 ± 0.06 nmol cm−2 min−1 (n = 5). Kinetic data thus indicates an increase in the number of active transporters, following stimulation. The incrased Gly‐Sar uptake was not accompanied by changes in hPepT1 mRNA, nor by measurable changes in cytosolic pH.

Conclusions: Short‐term stimulation with EGF and insulin caused an increase in hPepT1‐mediated uptake of Gly‐Sar in Caco‐2 cell monolayers, which could not be accounted for by changes in hPepT1 mRNA or proton‐motive driving force.
Muscle performance following fatigue induced by isotonic and quasi‐isometric contractions of rat extensor digitorum longus and soleus muscles in vitro
Authors: Vedsted P. , Larsen A. H. , Madsen K. , Sjøgaard G.
Published: May 2003

Aim: To study the effect of contraction mode on fatigue development.

Methods: Muscle fatigue was induced by isotonic and quasi‐isometric contractions in rat soleus (SOL) and extensor digitorum longus (EDL) muscles, using identical stimulation protocol (60 Hz, 400 ms s−1) for 100 s in SOL and 60 s in EDL. Fatigue was quantified as the decline in peak values of shortening, shortening velocity, relaxation and work during the isotonic contractions, and, correspondingly, of force, rate of force development, relaxation and work during the quasi‐isometric contractions. Maximal test contractions (60 Hz, 1.5 s) performed before and after fatigue were analysed for decline in force development (Fmax), rate of force development (dF/dtmax) and relaxation (−dF/dtmax).

Results: F
max declined to significantly lower values after isotonic than after quasi‐isometric fatiguing contractions (fatigued in percentage of unfatigued): 58.5 ± 6.4% vs. 64.4 ± 7.0% in SOL, and 30.4 ± 4.1% vs. 33.3 ± 3.6% in EDL, respectively. The same pattern was seen for dF/dtmax which decreased to: 46.3 ± 9.9% vs. 52.3 ± 8.5% in SOL, and 19.1 ± 4.3% vs. 22.3 ± 3.2% in EDL after isotonic and quasi‐isometric contractions, respectively. Similarly, when comparing fatigue development during the two contraction modes, the respective fatigue variables decreased more rapidly and to lower levels during isotonic vs. quasi‐isometric contractions. During maximal test contractions, the dynamic fatigue variables (±dF/dtmax) declined to significantly lower levels than Fmax.

Conclusions: Fatigue development was significantly larger during isotonic vs. quasi‐isometric contractions. The use of force as the only experimental fatigue variable may underestimate the functional impairment of fatigued muscle, neglecting the fatigue effect on time and length dimensions.
Strength, workload, anaerobic intensity and the immune response to resistance exercise in women
Authors: Miles M. P. , Kraemer W. J. , Nindl B. C. , Grove D. S. , Leach S. K. , Dohi K. , Marx J. O. , Volek J. S. , Mastro A. M.
Published: May 2003

Aim: The mechanism linking exercise intensity to the magnitude of the immune response is not completely understood. The purpose of this investigation was to determine whether the immune response to resistance exercise was associated with (1) changes in workload or (2) anaerobic exercise intensity.

Methods:  Previously untrained women underwent 6 months of resistance training for lower and upper body (TOTAL, n = 34) or for upper body alone (UPPER, n = 30). Lymphocyte subsets [T (CD3+), CD4+, CD8+, NK and B], functional markers (CD45RA+ and CD45RO+), and mitogen (phytohemagglutinin‐M, concanavalin A and pokeweed mitogen) and superantigen (staphylococcus a. cowans)‐stimulated proliferation were measured from blood samples collected pre‐ and post‐exercise for a squat resistance exercise consisting of six sets of 10 repetitions at 75% of one repetition maximum. This protocol was performed before (T0) and after 3 (T3) and 6 months (T6) of training.

Results:  Lymphocyte recruitment to the circulation and proliferation following resistance exercise did not differ between training groups at any time, although the TOTAL group performed at a higher workload as training progressed. With respect to anaerobic intensity, exercise‐induced increases in NK, CD4+, CD8+ and B lymphocyte concentrations were 42 (P = 0.07), 76 (P < 0.05), 72 (P < 0.05) and 242% (P < 0.01) greater in women in the highest compared with the lowest post‐exercise lactate quartiles. Lymphocyte proliferation did not differ between lactate quartiles.

Conclusions: Anaerobic intensity, rather than increased strength and workload, is associated with the number of lymphocytes recruited to the circulation, but not T and B cell proliferation responses.
Coronary smooth muscle adaptation to exercise: does it play a role in cardioprotection?
Authors: Bowles D. K. , Wamhoff B. R.
Published: May 2003

Substantial evidence exists supporting the role of chronic exercise in reducing the incidence and severity of coronary vascular disease. Physical inactivity is an independent risk factor for coronary heart disease suggesting that the cardioprotective effect of exercise is due, in part, to an intrinsic adaptation within the coronary vasculature. Surprisingly, a paucity of information exists regarding the intrinsic cellular changes within the coronary vasculature associated with exercise training and even less is known regarding the effect of physical activity on long‐term phenotypic modulation of coronary smooth muscle (CSM). The purpose of this symposium is to provide a concise update on the current knowledge regarding CSM adaptation to exercise training and the potential for these adaptations to contribute to exercise‐induced cardioprotection. The potential role of CSM in exercise‐induced cardioprotection will be approached from two perspectives. First, endurance exercise training effects on the regulation of coronary vasomotor tone via changes in CSM calcium regulation will be reviewed, i.e. short‐term functional adaptation. Secondly, we will discuss potential long‐term consequences of this altered calcium regulation, i.e. exercise‐induced phenotypic modulation of CSM. We propose that exercise training alters CSM intracellular calcium regulation to reduce Ca2+‐dependent activation of the contractile apparatus and Ca2+‐dependent gene transcription and increase activation of sarcolemmal potassium channels. The overall effect is to increase the gain of the vasomotor system and maintain a stable, contractile CSM phenotype.
Rates of deformation of an extensional growth fault/raft system (offshore Congo, West African margin) from combined accommodation measurements and 3‐D restoration
Authors: Rouby D. , Guillocheau F. , Robin C. , Bouroullec R. , Raillard S. , Castelltort S. , Nalpas T.
Published: May 2003

Abstracts

The aim of this paper is to quantify the evolution in time and space of the accommodation (space available for sedimentation) in the case of a growth fault structure resulting from gravity‐induced extension comprising a listric fault/raft system located along the West African margin. To achieve this, use was made of an original approach combining two complementary techniques (accommodation variation measurements and 3‐D restoration) in order to quantify vertical and horizontal displacement related to deformation, using a data set made up of a 3‐D seismic survey and well logs. We applied sequence stratigraphic principles to (i) define a detailed stratigraphic framework for the Albo‐Cenomanian and (ii) measure subsidence rates from accommodation variations. 3‐D restoration was used to (iii) reconstruct the evolution of the 3‐D geometry of the fault system. The rates of horizontal displacement of structural units were measured and linked to successive stages in the growth of the fault system.

Subsidence of the structural units exhibits three scales of variation: (1) long‐term variation (10 Ma) of c. 80 m Ma−1 for a total subsidence of about 1400 m, compatible with the general subsidence of a passive margin, and (2) short‐term variations (1–5 Ma) corresponding to two periods of rapid subsidence (about 150–250 m Ma−1) alternating with periods of moderate subsidence rate (around 30 m Ma−1). These variations are linked to the development of the fault system during the Albian (with downbuilding of the raft and development of the initial basin located in between). During the Cenomanian, the development of the graben located between the lower raft and the initial basin did not seem to affect the vertical displacements. (3) High‐frequency variations (at the scale of genetic unit sets) range between −50 and 250 m for periods of 0.2–2 Ma. Accommodation variations governed these cycles of progradation/retrogradation rather than sediment flux variations. In addition, the nine wells display a highly consistent pattern of variation in accommodation. This suggests that the genetic unit sets were controlled at a larger scale than the studied system (larger than 20 km in wavelength), for example, by eustatic variations. Translation rates are between 3 and 30 times higher than subsidence rates. Therefore, in terms of amplitude, the main parameter controlling the space available for sedimentation is the structural development of the fault system, that is to say, the seaward translation of the raft units, itself resulting from a regional gravity‐driven extension.
Linking hinterland evolution and continental basin sedimentation by using detrital zircon thermochronology: a study of the Khorat Plateau Basin, eastern Thailand
Authors: Carter A. , Bristow C. S.
Published: May 2003

The effectiveness of detrital zircon thermochronology as a means of linking hinterland evolution and continental basin sedimentation studies is assessed by using Mesozoic continental sediments from the poorly understood Khorat Plateau Basin in eastern Thailand. New uranium lead (U‐Pb) and fission‐track (FT) zircon data from the Phu Kradung Formation identify age modes at 141 ± 17 and 210 ± 24 Ma (FT) and 2456 ± 4, 2001 ± 4, 251 ± 3, and 168 ± 2 Ma (U‐Pb), which are closely similar to data from the overlying formations. The FT data record post‐metamorphic cooling, whereas the U‐Pb data record zircon growth events in the hinterland. Comparison is made between detrital zircon U‐Pb data from ancient and modern sources across Southeast Asia. The inherent stability of the zircon U‐Pb system means that 250 Myr of post‐orogenic sedimentary recycling fails to change the regional zircon U‐Pb age signature and this precludes use of the U‐Pb approach alone for providing unique provenance information.

Although the U‐Pb zircon results are consistent with (but not uniquely diagnostic of) the Qinling Orogenic Belt as the original source terrane for the Khorat Plateau Basin sediments, the zircon FT cooling data are more useful as they provide the key temporal link between basin and hinterland. The youngest zircon FT modes from the Khorat sequence range between 114 ± 6 (Phra Wihan Formation) and 141 ± 17 Ma (Phu Kradung Formation) that correspond to a Late Jurassic/Early Cretaceous reactivation event, which affected the Qinling Belt and adjacent foreland basins. The mechanism for regional Early Cretaceous erosion is identified as Cretaceous collision between the Lhasa Block and Eurasia. Thus, the Khorat Plateau Basin sediments might have originated from a reactivation event that affected a mature hinterland and not an active orogenic belt as postulated in previous models.
Post‐Jurassic tectono‐sedimentary evolution of the Northern Lusitanian Basin (Western Iberian margin)
Authors: Alves Tiago M. , Gawthorpe Robert L. , Hunt David W. , Monteiro José H.
Published: May 2003

Seismic reflection and well stratigraphic data are used to investigate the post‐Jurassic evolution of the Northern Lusitanian Basin, offshore west Iberia. Stratigraphic correlations between 11 exploration wells were attained in order to characterize the variations in depositional facies associated with salt tectonics. Latest Triassic–Hettangian salt, which generated multiple salt pillows during the Jurassic rifting, was reactivated after the early Aptian in two main phases. The first phase stretches from the late Turonian to the Maastrichtian. The second relates to Miocene tectonic inversion. The compression of the post‐salt overburden caused the amplification of Jurassic detachment folds, forming barriers to the westward progradation of sediment into distinct salt‐withdrawal sub‐basins. Particularly during the Miocene, thin‐skinned overburden shortening was accommodated by growing salt structures that suffered thrusting and extrusion. This structural style contrasts with that of salt‐scarce areas where a simple westerly tilted, fault‐bounded monocline was generated.
Incidence and prognosis of c‐KIT and FLT3 mutations in core binding factor (CBF) acute myeloid leukaemias
Authors: Care Rory S. , Valk Peter J. M. , Goodeve Anne C. , Abu‐Duhier Faisel M. , Geertsma‐Kleinekoort Wendy M. C. , Wilson Giu A. , Gari Mamdooh A. , Peake Ian R. , Löwenberg Bob , Reilly John T.
Published: May 2003

Summary. DNA from 110 adult de novo acute myeloid leukaemia (AML) patients exhibiting either inv(16) (n = 63) or t(8;21) (n = 47) was screened for mutations in the c‐KIT (exon 8 and Asp816) and FLT3 (ITD and Asp835) genes. c‐KIT exon 8 mutations were found in 15/63 (23·8%) inv(16) patients and 1/47 (2·1%) t(8;21) patients. c‐KIT Asp816 mutations were present in 5/63 (7·9%) inv(16) AML and 5/47 (10·6%) t(8;21) AML. FLT3 mutations were identified in five patients (7·9%) with inv(16) and three patients (5·6%) with t(8;21) AML. All mutations were mutually exclusive; 40% of inv(16) AML patients possessed either a c‐KIT or FLT3 mutation. c‐KIT exon 8 mutations were shown to be a significant factor adversely affecting relapse rate.
Biological and clinical features of low‐molecular‐weight heparin‐induced thrombocytopenia
Authors: Gruel Yves , Pouplard Claire , Nguyen Philippe , Borg Jeanne‐Yvonne , Derlon Annie , Juhan‐Vague Irène , Regnault Véronique , Samama Michel ,   The French Heparin‐Induced Thrombocytopenia Study Group
Published: May 2003

Summary. Heparin‐induced thrombocytopenia (HIT) is a common adverse effect of unfractionated heparin (UFH) therapy. In contrast, only a few patients have been reported with HIT following low‐molecular‐weight heparin (LMWH) therapy (LMW‐HIT). To define the clinical and biological characteristics of LMW‐HIT, 180 patients treated for suspected HIT at 15 French centres were investigated. Clinical history was recorded and HIT was confirmed in 59 patients with positive serotonin release assay results: 57 of them had high levels of antibodies (Abs) to heparin–platelet factor 4 complexes (H/PF4) and two had Abs to interleukin 8. Eleven patients were treated exclusively with LMWH (LMW‐HIT) and 48 with UFH either alone (UF‐HIT, n = 34) or combined with LMWH (UF/LMW‐HIT, n = 14). The LMW‐HIT and UF‐HIT groups were similar with respect to sex, age, platelet count before heparin therapy, frequency of bleeding and occurrence of disseminated intravascular coagulation. The interval to onset of HIT was longer in LMW‐HIT patients compared with UF‐HIT patients (P = 0·03). Severe thrombocytopenia (platelets < 15 × 109/l) was more frequent in the LMW‐HIT group (P = 0·04). Thrombosis occurred in three of 11 LMW‐HIT patients, i.e. as frequently as in UF‐HIT patients. LMW‐HIT is potentially severe and may be observed after longer heparin treatment compared with UF‐HIT. It is highly recommended, therefore, that platelet counts be monitored carefully whenever LMWH is administered.
Effects of Novelty Stress on Neuroendocrine Activities and Running Performance in Thoroughbred Horses
Authors: Hada T. , Onaka T. , Takahashi T. , Hiraga A. , Yagi K.
Published: May 2003

This study investigated the effects of novelty stress on neuroendocrine activities and running performance in Thoroughbred horses. First, to examine the neuroendocrine responses to novelty stress, we exposed horses to two types of novel environmental stimuli (audiovisual or novel field stimuli). After the stimuli, plasma concentrations of vasopressin, catecholamines and adrenocorticotropin (ACTH), as well as heart rates, were significantly increased in each experiment. Second, we investigated neuroendocrine activities during incremental exercise. Plasma concentrations of vasopressin, catecholamines, ACTH and blood lactate increased as the exercise load increased. Finally, we investigated the effects of novelty stimuli on neuroendocrine activities and running performance during supra‐maximal exercise (110% VHRmax). When the novelty stimuli were presented to horses, the increases in plasma vasopressin and catecholamines due to exercise load were significantly smaller than those in the control experiments. Blood lactate during supra‐maximal exercise was also significantly lower and total run time until exhaustion was prolonged in the novel environmental stimuli compared to the control. These results suggest that novelty stimuli facilitate vasopressin release from the posterior pituitary in addition to activating the sympatho‐adrenomedullary and the hypothalamic‐pituitary‐adrenocortical axes in thoroughbred horses, and increase exercise capacity, resulting in improvement of running performance during supra‐maximal exercise.
Regulation of Rat APJ Receptor Messenger Ribonucleic Acid Expression in Magnocellular Neurones of the Paraventricular and Supraopric Nuclei by Osmotic Stimuli
Authors: O'Carroll A.‐M. , Lolait S. J.
Published: May 2003

The novel apelin receptor (APJ receptor, APJR) has a restricted expression in the central nervous system suggestive of an involvement in the regulation of body fluid homeostasis. The endogenous ligand for APJR, apelin, is also highly concentrated in regions that are involved in the control of drinking behaviour. While the physiological roles of APJR and apelin are not fully known, apelin has been shown to stimulate drinking behaviour in rats and to have a regulatory effect on vasopressin release from magnocellular neurones of the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. To determine the role of APJR in the regulation of water balance, this study examined the effects of osmotic stimulation on the expression of APJR mRNA in the magnocellular PVN (mPVN) and SON of salt‐loaded and water‐deprived rats. Intake of 2% NaCl and water deprivation for 48 h induced expression of APJR mRNA in the mPVN and SON. Using dual‐label in situ hybridization histochemistry, we also investigated whether APJR is colocalized within vasopressin neurones in control, salt‐loaded and water‐deprived rats. APJR mRNA was found to colocalize with a small population of vasopressin‐containing magnocellular neurones in control and water‐deprived rats. Salt‐loading resulted in an increased colocalization of APJR and vasopressin mRNAs in the SON. These data verify a role for APJ receptors in body fluid regulation and suggest a role for apelin in the regulation of vasopressin‐containing neurones via a local autocrine/paracrine action of the peptide.