bluuebunny/crossref_metadata_2025 huggingface dataset:
Cannabis and sport
Authors: Saugy M , Avois L , Saudan C , Robinson N , Giroud C , Mangin P , Dvorak J
Published: June 2006

Background and objectives:Cannabis is on the list of prohibited substances in the practice of sport, although its performance enhancing effect has not yet been proved. Its popularity among the younger generations as a social drug puts cannabis at the top of the list of compounds detected by the anti-doping laboratories accredited by the World Anti-Doping Agency worldwide. The management of the results of urine analysis is quite difficult for the medical and disciplinary committees not only because of the social use of the substance, but also because of the interpretation of the analytical data from urine samples. This paper gives an overview of what is presently known about cannabis in relation with the practice of sport.

Methods:Review of literature on the cannabis and exercise, its effect in the body, and the problems with interpretation of results when it is detected in urine.

Results:The paper outlines the major effects of cannabis in the context of its social use and its use for sport activities. The difficulties in the interpretation of urine sample analysis results because of the protracted excretion time of the main metabolite, long after the intake, are described.

Conclusions:There is an urgent need for sport authorities to take measures necessary to avoid players misusing cannabis.
Inhaled β2agonists and performance in competitive athletes
Authors: Kindermann W , Meyer T
Published: June 2006

Objectives:To provide an overview of the current literature on the use of inhaled β2agonists in non-asthmatic competitive athletes, and to assess the performance enhancing effect of inhaled β2agonists.

Methods:Review of the literature.

Results:Twenty randomised, placebo controlled studies (19 double blind, one single blind) were located. Only three studies reported a performance enhancing effect of inhaled β2agonists. However, methodological shortcomings were most likely responsible for these findings (for example, non-elite athletes, inconsistent results in different tests, subgroups with above-average responsiveness).

Conclusions:This review reveals that there is no ergogenic potential of inhaled β2agonists in non-asthmatic athletes. In view of the epidemiology of asthma in athletes and the considerable workload involved in provision of therapeutic use exemptions the inclusion of inhaled β2agonists on the list of prohibited substances should be reconsidered.
Medicolegal aspects of doping in football
Authors: Graf-Baumann T
Published: June 2006

This article describes the historical background of the medicolegal aspects of doping in sports and especially in football. The definitions of legal terms are explained and the procedure of individual case management as part of FIFA’s approach to doping is presented. Finally, three medicolegal problems awaiting urgent solution are outlined: firstly, the difficulties in decision making arising from the decrease of the T/E ratio from 6 to 4; secondly, the therapeutic application of α-reductase inhibitors for male pattern baldness in the face of the classification of finasteride as a forbidden masking agent; and lastly, the increasing use of recreational drugs and its social and legal implications in positive cases.
Neoliberalism and the Environment in Latin America
Authors: Liverman Diana M. , Vilas Silvina
Published: June 2006

▪ Abstract  This review examines how neoliberal policies that include free trade and less government have altered environmental management of industry, forests, water, agricultural land, and fisheries in Latin America. We examine theories and case studies about the privatization and pricing of environmental services and common property resources, the environmental impacts of free trade, and the transfer of environmental management to local or nongovernmental institutions. We conclude that neoliberalism has had some profound influences on the environment and on environmental management in Latin America and that the implementation and impacts of neoliberal policies on local environments have varied greatly by nation and by place as a result of different political, institutional, economic, environmental, and social conditions. Although many studies of neoliberalism and environment paint a negative picture, there are places and people that have adapted well to and benefited from neoliberal policies. Unfortunately, judgments on the success of neoliberal policies are limited by data and by the lack of detailed and balanced case studies.
Recurrent hypoglycemia reduces the glucose sensitivity of glucose-inhibited neurons in the ventromedial hypothalamus nucleus
Authors: Song Zhentao , Routh Vanessa H.
Published: June 2006

Recurrent hypoglycemia blunts the brain's ability to sense and respond to subsequent hypoglycemic episodes. Glucose-sensing neurons in the ventromedial hypothalamus nucleus (VMN) are well situated to play a role in hypoglycemia detection. VMN glucose-inhibited (GI) neurons, which decrease their firing rate as extracellular glucose increases, are extremely sensitive to decreased extracellular glucose. We hypothesize that recurrent hypoglycemia decreases the glucose sensitivity of VMN GI neurons. To test our hypothesis, 14- to 21-day-old Sprague-Dawley rats were subcutaneously injected with regular human insulin (4 U/kg) or saline (control) for three consecutive days. Blood glucose levels 1 h after insulin injection on day 3 were significantly lower than on day 1, reflecting an impaired ability to counteract hypoglycemia. On day 4, the glucose sensitivity of VMN GI neurons was measured using conventional whole cell current-clamp recording. After recurrent insulin-induced hypoglycemia, VMN GI neurons only responded to a glucose decrease from 2.5 to 0.1, but not 0.5, mM. Additionally, lactate supplementation also decreased glucose sensitivity of VMN GI neurons. Thus our findings suggest that decreases in glucose sensitivity of VMN GI neurons may contribute to the impairments in central glucose-sensing mechanisms after recurrent hypoglycemia.
Spontaneous, homeostatic, and inflammation-induced sleep in NF-κB p50 knockout mice
Authors: Jhaveri K. A. , Ramkumar V. , Trammell R. A. , Toth L. A.
Published: June 2006

The dimeric transcription factor nuclear factor-κB (NF-κB) regulates several endogenous sleep-modulatory substances and thereby serves as a pivotal mediator of sleep-wake homeostasis. To further define the role of NF-κB in sleep regulation, we monitored sleep and temperature in mice that lack the p50 subunit of NF-κB [p50 knockout (KO) mice]. Compared with the control B6129PF2/J strain, p50 KO mice spend more time in slow-wave sleep (SWS) and rapid eye movement sleep (REMS) under normal conditions and show enhanced homeostatic recovery of sleep after sleep loss. p50 KO mice also show increased SWS and reduced REMS and temperature after the administration of lipopolysaccharide, yet they are behaviorally less responsive to challenge with influenza virus. These data support a role for NF-κB, and, in particular, for the p50 subunit, in the regulation of sleep in healthy mice and in mice experiencing immune challenge.
Hyperhomocysteinemia increases arterial permeability and stiffness in mice
Authors: Mullick Adam E. , Zaid Ussama B. , Athanassious Christian N. , Lentz Steven R. , Rutledge John C. , Symons J. David
Published: June 2006

We have reported that hyperhomocysteinemia (HHcy) evoked by folate depletion increases arterial permeability and stiffness in rats and that low folate without HHcy increases arterial permeability in mice. In this study, we hypothesized that HHcy independently increases arterial permeability and stiffness in mice. C57BL/6J mice that received rodent chow and water [control (Con), n = 12] or water supplemented with 0.5% l-methionine (HHcy, n = 12) for 18 ± 3 wk had plasma homocysteine concentrations of 8 ± 1 and 41 ± 1 μM, respectively ( P < 0.05), and similar liver folate (∼12 ± 2 μg folate/g liver). Carotid arterial permeability, assessed as dextran accumulation using quantitative fluorescence microscopy, was greater in HHcy (3.95 ± 0.4 ng·min−1·cm−2) versus Con (2.87 ± 0.41 ng·min−1·cm−2) mice ( P < 0.05). Stress versus strain curves generated using an elastigraph indicated that 1) maximal stress (N/mm2), 2) physiological stiffness (low-strain Young's modulus, mN/mm), and 3) maximal stiffness (high-strain Young's modulus, N/mm) were higher ( P < 0.05) in aortas from HHcy versus Con mice. Thus, chronic HHcy increases arterial permeability and stiffness. Carotid arterial permeability also was assessed in age-matched C57BL/6J mice before and after incubation with 1) xanthine (0.4 mg/ml)/xanthine oxidase (0.2 mg/ml; X/XO) to generate superoxide anion (O2−) or 50 μM dl-homocysteine in the presence of 2) vehicle, 3) 300 μM diethylamine-NONOate (DEANO; a nitric oxide donor), or 4) 10−3M 4,5-dihydroxy-1,3-benzene disulfonic acid (tiron; a nonenzymatic intracellular O2−scavenger). Compared with preincubation values, X/XO and dl-homocysteine increased ( P < 0.05) permeability by 66 ± 11% and 123 ± 8%, respectively. dl-Homocysteine-induced increases in dextran accumulation were blunted ( P < 0.05) by simultaneous incubation with DEANO or tiron. Thus, acute HHcy increases arterial permeability by generating O2−to an extent whereby nitric oxide bioavailability is reduced.
Increased serum erythropoietin but not red cell production after 4 wk of intermittent hypobaric hypoxia (4,000–5,500 m)
Authors: Gore Christopher J. , Rodríguez Ferran A. , Truijens Martin J. , Townsend Nathan E. , Stray-Gundersen James , Levine Benjamin D.
Published: June 2006

This study tested the hypothesis that athletes exposed to 4 wk of intermittent hypobaric hypoxia exposure (3 h/day, 5 days/wk at 4,000–5,500 m) or double-blind placebo increase their red blood cell volume (RCV) and hemoglobin mass (Hbmass) secondary to an increase in erythropoietin (EPO). Twenty-three collegiate level athletes were measured before (Pre) and after (Post) the intervention for RCV via Evans blue (EB) dye and in duplicate for Hbmassusing CO rebreathing. Hematological indexes including EPO, soluble transferrin receptor, and reticulocyte parameters were measured on 8–10 occasions spanning the intervention. The subjects were randomly divided among hypobaric hypoxia (Hypo, n = 11) and normoxic (Norm, n = 12) groups. Apart from doubling EPO concentration 3 h after hypoxia there was no increase in any of the measures for either Hypo or Norm groups. The mean change in RCV from Pre to Post for the Hypo group was 2.3% (95% confidence limits = −4.8 to 9.5%) and for the Norm group was −0.2% (−5.7 to 5.3%). The corresponding changes in Hbmasswere 1.0% (−1.3 to 3.3%) for Hypo and −0.3% (−2.6 to 3.1%) for Norm. There was good agreement between blood volume (BV) from EB and CO: EB BV = 1.03 × CO BV + 142, r2= 0.85, P < 0.0001. Overall, evidence from four independent techniques (RCV, Hbmass, reticulocyte parameters, and soluble transferrin receptor) suggests that INTERMITTENT HYPOBARIC HYPOXIA EXPOSURE did not accelerate erythropoiesis despite the increase in serum EPO.
Postnatal developmental changes in CO2sensitivity in rats
Authors: Davis S. E. , Solhied G. , Castillo M. , Dwinell M. , Brozoski D. , Forster H. V.
Published: June 2006

Ventilatory sensitivity to CO2in awake adult Brown Norway (BN) rats is 50–75% lower than in adult Sprague-Dawley (SD) and salt-sensitive Dahl S (SS) rats. The purpose of the present study was to test the hypothesis that this difference would be apparent during the development of CO2sensitivity. Four litters of each strain were divided into four groups such that rats were exposed to 7% inspired CO2for 5 min in a plethysmograph every third day from postnatal day (P) 0 to P21 and again on P29 and P30. From P0 to P14, CO2exposure increased pulmonary ventilation (V̇e) by 25–50% in the BN and SD strains and between 25 to over 200% in the SS strain. In all strains beginning around P15, the response to CO2increased progressively reaching a peak at P19–21 when V̇e during hypercapnia was 175–225% above eucapnia. There were minimal changes in CO2sensitivity between P21 and P30, and at both ages there were minimal between-strain differences. At P30, the response to CO2in the SS and SD strains was near the adult response, but the response in the BN rats was 100% greater at P30 than in adults. We conclude that 1) CO2-sensing mechanisms, and/or mechanisms downstream from the chemoreceptors, change dramatically at the age in rats when other physiological systems are also maturing (∼P15), and 2) there is a high degree of age-dependent plasticity in CO2sensitivity in rats, which differs between strains.
Effect of caffeine supplementation on the extracellular heat shock protein 72 response to exercise
Authors: Whitham Martin , Walker Gary J. , Bishop Nicolette C.
Published: June 2006

The stimulus for the release of 72-kDa heat shock protein (HSP72) during exercise in humans is currently unclear. Recent evidence in an animal model is suggestive of an involvement of catecholamines. The present study, therefore, investigated the effect of caffeine supplementation, a known stimulator of sympathetic activity, on the extracellular (e)HSP72 response to prolonged exercise. Ten healthy male endurance-trained cyclists were recruited (age: 21 ± 1 yr, maximum O2uptake 61.1 ± 1.7 ml·kg−1·min−1, mean ± SE). Each subject was randomly assigned to ingest either 6 mg/kg body mass of caffeine (Caff) or placebo (Pla) 60 min before one of two 90-min bouts of cycling at 74 ± 1% maximum O2uptake. Trials were performed at least 7 days apart in a counterbalanced design. Venous blood samples were collected by venepuncture at pretreatment, preexercise, postexercise, and 1 h postexercise. Serum caffeine and plasma catecholamines were determined using a spectrophotometric assay and high-performance liquid chromatography, respectively. Plasma HSP72 and cortisol were determined by ELISA. Serum caffeine concentrations were significantly increased throughout Caff, while no increases were detected in Pla. Caffeine supplementation and exercise was associated with a greater eHSP72 response than exercise alone (postexercise Caff 8.6 ± 1.3 ng/ml; Pla 5.9 ± 0.9 ng/ml). This greater eHSP72 response was associated with a greater epinephrine response to exercise in Caff. There was a significant increase in norepinephrine and cortisol, with no intertrial differences. The present data suggest that, in humans, catecholamines may be an important mediator of the exercise-induced increase in eHSP72 concentration.
Age-dependent changes in the mechanical properties of tail tendons in TGF-β inducible early gene-1 knockout mice
Authors: Bensamoun Sabine F. , Tsubone Tetsu , Subramaniam Malayannan , Hawse John R. , Boumediene Emir , Spelsberg Thomas C. , An Kai-Nan , Amadio Peter C.
Published: June 2006

The purpose of this study is to investigate age-dependent changes in the architecture and mechanical properties of tendon in TGF-β inducible early gene-1 (TIEG) knockout mice. Wild-type and TIEG knockout mice, aged 1, 2, and 15 mo, were used. The mechanical properties of tail tendons isolated from these mice were determined using uniaxial tensile ramp (0.05 mm/s) and relaxation (5 mm/s) tests, with a strain of 10%. Mechanical parameters (Young's modulus from the ramp test; fast and static stresses from the relaxation test) were measured and recorded. The structure of the tail tendon fascicle was characterized by transmission electron microscopy. The results of the mechanical testing revealed no significant difference between the knockout and wild-type groups at 1 or 15 mo of age. However, the fascicles of the knockout mice at 3 mo of age exhibited decreased fast and static stresses compared with those of the wild-type mice. Electron microscopy revealed an increase in fibril size in the knockout mouse tendons relative to wild-type controls at 1 and 3 mo of age. These data indicate an important role for TIEG in tendon microarchitecture and strength in adult mice.
Influence of sex steroid hormones on cerebrovascular function
Authors: Krause Diana N. , Duckles Sue P. , Pelligrino Dale A.
Published: June 2006

The cerebral vasculature is a target tissue for sex steroid hormones. Estrogens, androgens, and progestins all influence the function and pathophysiology of the cerebral circulation. Estrogen decreases cerebral vascular tone and increases cerebral blood flow by enhancing endothelial-derived nitric oxide and prostacyclin pathways. Testosterone has opposite effects, increasing cerebral artery tone. Cerebrovascular inflammation is suppressed by estrogen but increased by testosterone and progesterone. Evidence suggests that sex steroids also modulate blood-brain barrier permeability. Estrogen has important protective effects on cerebral endothelial cells by increasing mitochondrial efficiency, decreasing free radical production, promoting cell survival, and stimulating angiogenesis. Although much has been learned regarding hormonal effects on brain blood vessels, most studies involve young, healthy animals. It is becoming apparent that hormonal effects may be modified by aging or disease states such as diabetes. Furthermore, effects of testosterone are complicated because this steroid is also converted to estrogen, systemically and possibly within the vessels themselves. Elucidating the impact of sex steroids on the cerebral vasculature is important for understanding male-female differences in stroke and conditions such as menstrual migraine and preeclampsia-related cerebral edema in pregnancy. Cerebrovascular effects of sex steroids also need to be considered in untangling current controversies regarding consequences of hormone replacement therapies and steroid abuse.
Cardiopulmonary resuscitation in a rat model of chronic myocardial ischemia
Authors: Fang Xiangshao , Tang Wanchun , Sun Shijie , Huang Lei , Chang Yun-Te , Huang Zitong , Weil Max Harry
Published: June 2006

Our group has developed a rat model of cardiac arrest and cardiopulmonary resuscitation (CPR). However, the current rat model uses healthy adult animals. In an effort to more closely reproduce the event of cardiac arrest and CPR in humans with chronic coronary disease, a rat model of coronary artery constriction was investigated during cardiac arrest and CPR. Left coronary artery constriction was induced surgically in anesthetized, mechanically ventilated Sprague-Dawley rats. Echocardiography was used to measure global cardiac performance before surgery and 4 wk postsurgery. Coronary constriction provoked significant decreases in ejection fraction, increases in left ventricular end-diastolic volume, and increases left ventricular end-systolic volume at 4 wk postintervention, just before induction of ventricular fibrillation (VF). After 6 min of untreated VF, CPR was initiated on three groups: 1) coronary artery constriction group, 2) sham-operated group, and 3) control group (without preceding surgery). Defibrillation was attempted after 6 min of CPR. All the animals were resuscitated. Postresuscitation myocardial function as measured by rate of left ventricular pressure increase at 40 mmHg and the rate of left ventricular pressure decline was more significantly impaired and left ventricular end-diastolic pressure was greater in the coronary artery constriction group compared with the sham-operated group and the control group. There were no differences in the total shock energy required for successful resuscitation and duration of survival among the groups. In summary, this rat model of chronic myocardial ischemia was associated with ventricular remodeling and left ventricular myocardial dysfunction 4 wk postintervention and subsequently with severe postresuscitation myocardial dysfunction. This model would suggest further clinically relevant investigation on cardiac arrest and CPR.
Particle Size of Hydroxyapatite Granules Calcified from Red Algae Affects the Osteogenic Potential of Human Mesenchymal Stem Cells in vitro
Authors: Weissenböck Martina , Stein Elisabeth , Undt Gerhard , Ewers Rolf , Lauer Günter , Turhani Dritan
Published: June 2006

Hydroxyapatite (HA) microparticles as a carrier in an injectable tissue-engineered bone filler are considered promising candidates for the treatment of small bone defects in the craniomaxillofacial region. HA granules calcified from red algae, varying in size, were evaluated in vitro for their suitability to be used as a carrier for human mesenchymal stem cells (hMSCs). Three groups of granules were produced in grain sizes of 10–100, 200–500 and 600–1,000 µm. After seeding and culturing hMSCs under osteogenic differentiation conditions onto HA particles for 3, 6 and 9 days, cellular proliferation (tetrazolium salt, XTT), alkaline phosphatase (ALP)-specific activity and total protein synthesis were investigated. The osteoblastic phenotype of the cells was evaluated by assaying the bone-specific genes osteocalcin, osteopontin and collagen type I. XTT assay revealed significantly higher (p < 0.01) proliferation of cells grown on the smallest grain size after 9 days of culture. Regarding ALP-specific activity, significantly higher levels of activity were detected in cells grown on the smallest grain size. Different grain sizes had no significant effects on the secretion of osteocalcin and osteopontin. Collagen type I production was significantly higher (p < 0.05) in cells grown on the biggest grain size in comparison with the two other grain sizes. These results show that the particle size of HA microparticles affects the osteogenic potential of cultured hMSCs and lead to the conclusion that particle size has differential effects on ALP-specific activity and collagen type I production.
Morphology and Function of Ovine Articular Cartilage Chondrocytes in 3-D Hydrogel Culture
Authors: Schagemann Jan C. , Mrosek Eike H. , Landers Rüdiger , Kurz Haymo , Erggelet Christoph
Published: June 2006

Different cell- and biomaterial-based tissue engineering techniques are under investigation to restore damaged tissue. Strategies that use chondrogenic cells or tissues in combination with bioresorbable delivery materials are considered to be suitable to regenerate bio-artificial cartilage. Three-dimensional (3-D) cell embedding techniques can provide anchorage-independent cell growth and homogenous spatial cell arrangement, which play a key role in the maintenance of the characteristic phenotype and thus the formation of differentiated tissue. We developed a new injectable high water content (90%) hydrogel formulation with 5% sodium alginic acid and 5% gelatin as a temporary supportive intercellular matrix for 3-D cell culture. The objective was to determine whether the in vitro hydrogel culture of chondrocytes could preserve hyaline characteristics and thus could provide cartilage regeneration in vitro. Chondrocytes harvested from knee joints of skeletally mature sheep were cultured 3-D in hydrogel (7 × 106 cells/ml, 2.8-µl beads) for up to 10 weeks. Cell morphology and viability were evaluated with light microscopy, and proliferative activity was assessed with antibromodeoxyuridine immunofluorescence. Expression of collagens type I (COL1) and II (COL2), cartilage proteoglycans (PG) and hyaluronan synthases (HAS) were studied immunohistochemically. We observed that up to 36% of chondrocytes proliferated, while almost 100% presented a differentiated spheroidal phenotype. After an initial decrease at 2 weeks, cell density recovered to 85% of the initial absolute value at 10 weeks. Expression of hyaline matrix molecules resembled the in vivo pattern with increasing spatial deposition of PG and COL2. The proportion of PG-positive cells increased from initially 13 to 53% after 10 weeks, in contrast to consistently 100% COL2-positive cells. We conclude that 3-D hydrogel culture, even without mechanical stimulation or growth factor application, can keep chondrocytes in a differentiated state and provides a chondrogenic cell environment for in vitro cartilage regeneration for at least 10 weeks. Moreover, this hydrogel appears to be a suitable cell delivery material for subsequent in vivo implantation.
Effects of Epidermal Growth Factor and Keratinocyte Growth Factor on the Growth of Oropharyngeal Keratinocytes in Coculture with Autologous Fibroblasts in a Three-Dimensional Matrix
Authors: Blaimauer Karin , Watzinger Elisabeth , Erovic Boban M. , Martinek Helga , Jagersberger Tamara , Thurnher Dietmar
Published: June 2006

Tissue engineering of oropharyngeal mucosa is rendered complex by the fact that oropharyngeal keratinocytes are difficult to culture in the long term and do not grow well after several subcultivations. Three populations of oropharyngeal keratinocytes were isolated by a method based on different levels of β1-integrin expression. In particular, keratinocytes were isolated between cell fractions that adhere rapidly on collagen-IV-coated culture dishes (RAC-IV) and populations that are less adherent (RAC-IV-D). The total fraction of both subpopulations served as a control (RAC-IV-T). The epidermal growth factor (EGF) and the keratinocyte growth factor (KGF) were examined with regard to their effects on the growth of the three populations. Growth curves of all three cell fractions grown with or without EGF were generated, and different concentrations of EGF and KGF were tested. EGF did not change any growth characteristics of the cells, with the exception of the speed of growth. Best growth was achieved with a physiologic EGF concentration of 0.15–1.5 ng/ml and a KGF concentration of 15 ng/ml. Finally, we cocultured oropharyngeal keratinocytes and their autologous fibroblasts in a three-dimensional matrix using Matrigel™. Oropharyngeal keratinocytes grown in coculture formed larger colonies than keratinocytes grown without fibroblasts. In conclusion, we were able to optimize the supplement of EGF and KGF in standard medium for the long-term culture of primary oropharyngeal keratinocytes. The use of Matrigel as a scaffold for three-dimensional cocultures of oropharyngeal keratinocytes and fibroblasts might signify a step forward in the development of a transplantable mucosa construct.
Percutaneous Coronary Intervention in a Patient with Congenital Factor XI Deficiency and Acquired Inhibitor
Authors: Mungee Sudhir , Lapin Reuven , Cavusoglu Erdal , Clark Luther T. , Marmur Jonathan D.
Published: June 2006

Background: Factor XI deficiency has been associated with bleeding diathesis mostly secondary to trauma and post-operatively depending on the severity of deficiency. Cases with factor XI deficiency having undergone cardiac surgery and coronary intervention after appropriate replacement therapy have been reported in the past. The presence of inhibitor in factor XI deficiency poses a hematological challenge and literature regarding coronary intervention in such patients is limited. Immunosuppressive therapy, plasma exchange and factor VII product transfusions have been used prior to cardiac interventions in few such reported cases. Method: We report our approach in such a case of Percutaneous Transluminal Coronary Angioplasty in a 72-year-old male of Jewish origin who has congenital factor XI deficiency complicated with acquired inhibitor. Results: In some cases, the acuity of the coronary syndrome may mandate immediate coronary intervention. However, patient’s history of factor XI deficiency and acquired inhibitor pose a major dilemma of further course of action. We performed percutaneous balloon angioplasty in this case with no anti-coagulant and with favorable outcome. Conclusion: Under these circumstances of significant coagulation disorder and based on the case report, we recommend that balloon angioplasty be undertaken with no additional anti-coagulation other than Aspirin.
Cardiomyopathy Related to Antimalarial Therapy with Illustrative Case Report
Authors: Costedoat-Chalumeau Nathalie , Hulot Jean-Sebastien , Amoura Zahir , Delcourt Annick , Maisonobe Thierry , Dorent Richard , Bonnet Nicolas , Sablé Régis , Lechat Philippe , Wechsler Bertrand , Piette Jean-Charles
Published: June 2006

The antimalarial agents, chloroquine (CQ) and hydroxychloroquine (HCQ) are used in long-term treatment of connective tissue diseases and dermatological disorders and are generally regarded as safe. We present one case of cardiotoxicity in a 59-year-old woman treated with antimalarials during 13 years for a discoid lupus erythematosus. She progressively developed conduction disturbances and congestive heart failure (CHF). When the diagnosis of antimalarials toxicity was suspected, CQ was withdrawn. However, heart transplantation had to be performed in the following 4 months for severe CHF. Indeed, rare but severe cardiotoxicity may develop following prolonged use of antimalarials with both conduction disturbances (45 patients) and CHF (25 patients). These cardiac toxic effects have been reported with CQ and less frequently with HCQ use alone. Diagnoses are often delayed since the toxicity of the drug might be misattributed to other factors in these patients. The endomyocardial biopsy, or in some cases the muscle biopsy, are essential to confirm the antimalarials toxicity. Antimalarials have been stopped in 12 cases of CHF, leading to improvement in 8 cases (within 3 months to 5 years) and to deaths or to heart transplantation in 4 cases (within 1 week to 3 months). In the latter cases, as in our patient, the lack of improvement may have been explained by the severity of the cardiomyopathy at diagnosis and the short delay since withdrawal. As a consequence, the potential for reversibility and the severity in undiagnosed cases of these toxic cardiomyopathies emphasize the importance of recognizing early signs of toxicity in order to withdraw antimalarials before the occurrence of life-threatening CHF.
Thymus Involution and Cerebral White Matter Damage in Extremely Low Gestational Age Neonates
Authors: Kuban Joshua David , Allred Elizabeth N. , Leviton Alan
Published: June 2006

Background: Among newborns who die, those who have cerebral white matter damage are more likely than others to have thymus involution and low thymus weights. Objective: We sought to evaluate in a population of preterm newborns who did not die if those who developed a cerebral white matter damage (as defined by an echolucency) are more likely than others to have thymus involution as assessed on chest radiographs. Method: The 89 infants whose data were evaluated were born before the 28th week of gestation, had at least one chest radiograph within the first 2 days of life (to determine thymus size), and at least one cranial ultrasonogram to assess for white matter echolucency. Results: Eighty-five percent of these infants had a small thymus within the first 2 weeks of life. Median time to thymus involution in those born before the 26th week of gestation was 36 h, and in those born during or after the 26th week of gestation was 140 h. Infants who developed involution before the median time in their respective gestational age groups were classified as early involuters (group 1) and were compared to their peers with late/no involution (group 2). Infants with an echolucency were more likely to have had early involution than infants without an echolucency (89% vs. 44%) (p = 0.01). This relationship was not distorted by potential confounders. The echolucency odds ratio associated with early thymus involution was consistently above 8 in all strata of the sample. Conclusion: These results are consistent with the possibility that early thymus involution and neonatal white matter damage are not independent phenomena and may have common antecedents.
Mechanism of Non-Capacitative Ca2+ Influx in Response to Bradykinin in Vascular Endothelial Cells
Authors: Leung Pan-Cheung , Cheng Kwong-Tai , Liu Cuiling , Cheung Wing-Tai , Kwan Hiu-Yee , Lau Kin-Ling , Huang Yu , Yao Xiaoqiang
Published: June 2006

Bradykinin is a potent vasoactive nonapeptide. It elicits a rise in cytosolic Ca2+ (Ca2+)i in endothelial cells, resulting in Ca2+-dependent synthesis and release of endothelial vasodilators. In the present study, we investigated the mechanism of bradykinin-induced Ca2+ influx in primary cultured rat aortic endothelial cells and in a mouse heart microvessel endothelial cell line (H5V). Bradykinin-induced Ca2+ influx was resolved into capacitative Ca2+ entry (CCE) and non-CCE. The non-CCE component was inhibited by a B2 receptor antagonist (HOE140; 1 µM) and a phospholipase C (PLC) inhibitor (U73122; 10 µM). The action of bradykinin could be mimicked by 1-oleoyl-2-acetyl-glycerol, an analogue of diacylglycerol (DAG), and by RHC80267, a DAG-lipase inhibitor. Immunoblots showed that TRPC6 was one of the main TRPC channels expressed in endothelial cells. Transfection of H5V cells with two siRNA constructs against TRPC6 both markedly reduced the TRPC6 protein level and, at the same time, decreased the percentage of cells displaying bradykinin-induced non-CCE. siRNA transfection also reduced the magnitude of non-CCE among the cells responding to bradykinin. Taken together, our data suggest that bradykinin-induced non-CCE is mediated via the B2-PLC pathway, and that DAG may be involved in this process. Further, TRPC6 is one of the important channels participating in bradykinin-induced non-CCE in endothelial cells.
Oral but Not Parenteral Aspirin Upregulates COX-2 Expression in Rat Stomachs
Authors: Mashita Yuji , Taniguchi Masaki , Yokota Aya , Tanaka Akiko , Takeuchi Koji
Published: June 2006

Aim: We compared the ulcerogenic effects of aspirin (ASA) and indomethacin in the rat gastric mucosa depending on the route of administration, together with the expression of COX-2. Methods: Animals fasted for 18 h were given ASA or indomethacin, either p.o. or s.c., and the stomach was examined 4 h later. Results: Indomethacin decreased mucosal PGE2 level, increased gastric motility, and caused gastric lesions with the up-regulation of COX-2 expression, irrespective of the route of administration. ASA induced both damage and COX-2 expression in the stomach when given p.o. but not s.c., despite decreasing the PGE2 level similarly via either route of administration. Gastric motility was temporarily increased and gastric potential difference (PD) was markedly decreased by ASA given p.o. PGE2 and atropine, although preventing ASA-induced gastric lesions as well as hypermotility, affected neither the COX-2 expression nor PD reduction induced by p.o. ASA. By contrast, the COX-2 expression induced by indomethacin was prevented by both PGE2 and atropine. Conclusion: ASA given p.o. caused damage in the stomach, together with the up-regulation of COX-2 expression, and this expression may be due to the topical irritative action, rather than being a result of PG deficiency. The expression of COX-2 after indomethacin is associated with gastric hypermotility due to PG deficiency.
Relationship of Underlying Abnormalities in Rectal Sensitivity and Compliance to Distension with Symptoms in Irritable Bowel Syndrome
Authors: Lee Kwang Jae , Kim Jin Hong , Cho Sung Won
Published: June 2006

Background/Aims: Abnormalities in rectal physiology play an important role in the genesis of symptoms in irritable bowel syndrome (IBS). However, their relationship to symptoms is unclear. Our aim was to investigate the association of abnormalities in rectal sensitivity and compliance to specific symptoms in IBS. Methods: Fifty-six IBS patients and 14 healthy controls participated in this study. The intensities of individual IBS symptoms in the past 4 weeks were scored on a graded 5-point Likert scale. Using a barostat, isobaric rectal distensions were performed before and after a meal. Results: Rectal hypersensitivity and hypocompliance in the fasting state were observed in 68 and 52% of IBS patients, respectively. Postprandial hypersensitivity of the rectum was significantly more prevalent in the diarrhea-predominant IBS (D-IBS) group compared to the constipation-predominant IBS (C-IBS) group. The D-IBS group showed a significant postprandial decrease in rectal compliance, but the C-IBS group did not. A significant correlation was observed between a sense of incomplete evacuation and increased bowel movements with postprandial rectal hypersensitivity or hypocompliance. Conclusion: A sense of incomplete evacuation and increased bowel movements are related to postprandial abnormalities in rectal sensitivity and compliance to distension. The other IBS symptoms do not seem to predict such abnormalities.
Ketoconazole-Tacrolimus Coadministration in Kidney Transplant Recipients: Two-Year Results of a Prospective Randomized Study
Authors: El-Dahshan Khalid Farouk , Bakr Mohamed Adel , Donia Ahmed Farouk , Badr Ali El-Sayed , Sobh Mohamed Abdel-Kader
Published: June 2006

Background/Aims: In developing countries, kidney transplantation is greatly hindered by financial problems, especially due to costly newer immunosuppressive medications. Ketoconazole increases blood levels of tacrolimus and cyclosporine through inhibition of cytochrome P450 microsomal enzymes. We previously reported on the 6-month safety and the outstanding impact on treatment costs of the ketoconazole-tacrolimus combination in kidney transplant recipients. Data of this combination are still lacking in the literature. We hereby report on the 2-year results of our trial. Methods: This prospective, randomized study included 70 live-donor kidney transplant recipients receiving tacrolimus (age 16–45 years, 54 males and 16 females). Patients were randomized into two equal groups: group 1, where ketoconazole 100 mg/day was added, and group 2 (control group). Results: After 2 years, group 1 (ketoconazole) patients still showed a highly significant reduction of the tacrolimus dose (by 53.8%) and cost (by 52.9%) compared with the control group (p < 0.001) and a significant improvement in graft function in comparison to their own initial graft function (p = 0.002). Throughout the 2 years, no side effects of ketoconazole were noted. Conclusion: We conclude that the long-term ketoconazole-tacrolimus combination therapy in kidney transplant recipients during the 2 years is safe, has an outstanding impact on treatment costs and improves graft outcome.
The Sertoli Cell – A Hormonal Target and ‘Super’ Nurse for Germ Cells That Determines Testicular Size
Authors: Petersen Cecilia , Söder Olle
Published: June 2006

The somatic Sertoli cell plays an essential role in embryonic determination of male somatic sex and in spermatogenesis during adult life. One individual Sertoli cell supplies a clone of developing germ cells with nutrients and growth factors and it is well established that the number of Sertoli cells present is closely correlated to both testicular size and sperm output. Sertoli cells continue to proliferate and differentiate until the beginning of puberty, when they cease dividing and start nursing the germ cells. At this point in time, the future capacity of the testis for sperm production has thus been determined. Prior to puberty the Sertoli cells are immature and differ considerably with respect to morphology and biochemical activity from the mature cell. The several investigations that have focused on hormonal and paracrine regulation of the functions of the mature cell are reviewed here, but the mechanisms underlying the maturation and general maintenance of well-functioning Sertoli cells remain obscure. An alarming decline in male reproductive health has been observed in several Western countries during recent decades. Disturbance of Sertoli cell differentiation is thought to be involved in the pathogenesis of both a poor sperm count and testicular cancer. It is speculated that environmental agents that disrupt the estrogenic/androgenic balance in the testis may play a role in this connection.
Central Application of IGF-1 Postpones Time of Vaginal Opening in Normally Fed, but Not in Food-Restricted Rats
Authors: Zeinoaldini S. , Swarts J.J.M. , Van de Heijning B.J.M.
Published: June 2006

Background/Aims: Central but also peripheral IGF-1 is suggested to play a role in the initiation of puberty as it directly affects GnRH synthesis and release. A possible intermediate in the effects of IGF-1 on puberty might be the adiposity-signaling hormone leptin, whose plasma levels are decreased in food-restricted (FR) rats. Methods: IGF-1 was chronically centrally infused in 23-day-old prepubertal female rats which were either normally fed or 30% FR, and the effects on time of vaginal opening (VO) and plasma leptin levels were monitored. Results: FR treatment postponed time of VO and decreased plasma leptin levels. In normally fed rats centrally infused with IGF-1, time of VO was found to be postponed to the same extent as FR treatment did. The IGF-1 infusion did not affect plasma leptin levels in normally fed animals but increased leptin levels in the FR group compared to controls. Daily food intake was equal between all groups but body weight course was lower in FR rats. IGF-1 treatment did not significantly affect food intake or body weight course. Conclusion: FR treatment delays the moment of vaginal opening to the same extent as observed in normally fed rats that were centrally infused with IGF-1.
Effect of Vitamin A on the CD44 Expression in the Small Intestine of Rats with Obstructive Jaundice
Authors: Sen Meral , Inan Aydın , Yenidünya Sibel , Ergin Metin , Dener Cenap
Published: June 2006

Hypothesis: In this study, the influence of obstructive jaundice on the CD44 expression in the rat small intestine and the alterations of this CD44 expression by vitamin A given intraperitoneally (200 IU/g/day) are evaluated. Materials and Methods: In a prospective animal model study, 32 Sprague-Dawley rats were randomized into four groups: group A rats (n = 8) underwent sham operation and were given daily saline intraperitoneally for 2 weeks (sham + saline); group B animals (n = 8) underwent sham operation and were given daily vitamin A intraperitoneally for 2 weeks (sham + vitamin A); group C rats (n = 8) underwent common bile duct ligation and were given daily saline intraperitoneally for 2 weeks (obstructive jaundice + saline), and group D animals (n = 8) underwent common bile duct ligation and were given daily vitamin A intraperitoneally for 2 weeks (obstructive jaundice + vitamin A). After 2 weeks, standardized jejunum and ileum segments were harvested from all animals. The expression of CD44 on the cell surface was evaluated immunohistochemically. Comparisons among the four groups were done. Results: The plasma bilirubin, aspartate transaminase, alanine transaminase, alkaline phospatase, and γ-glutamyltransferase levels in groups C and D (obstructive jaundice groups) were higher than those in groups A and B (sham groups; p < 0.05). There was no difference between groups A and B (sham groups) with regard to the number of cells expressing surface CD44 in jejunum and ileum. When groups A and B were compared with group C (obstructive jaundice + saline) animals, the number of cells expressing surface CD44 was significantly decreased in both jejunum and ileum in group C. The difference between sham groups (A and B) and group C was found to be significant (p < 0.05). When group D (obstructive jaundice + vitamin A) was compared with group C (obstructive jaundice + saline), the number of cells expressing surface CD44 was significantly increased in jejunum and ileum in group D animals (p < 0.05), higher than in the sham groups (A and B). The difference between group D and sham groups (A and B) was found to be significant (p < 0.05). Conclusion: Obstructive jaundice for 2 weeks significantly decreased the CD44 expression in the rat small intestine. We found that daily intraperitoneal administration of vitamin A in rats with obstructive jaundice for 2 weeks significantly restored the impaired CD44 expression.
Uncinatectomy: A Novel Surgical Option for the Management of Intraductal Papillary Mucinous Tumors of the Pancreas
Authors: Sharma Mahesh S. , Brams David M. , Birkett Desmond H. , Munson J. Lawrence
Published: June 2006

An intraductal papillary mucinous tumor (IPMT) is a rare cystic lesion of the pancreas, comprising only 1% of all pancreatic exocrine neoplasms. The prognosis for these lesions is typically favorable as compared with invasive ductal carcinomas. Nevertheless, the management of IPMTs involves surgical resection due to their malignant potential. When located in the pancreatic head, the conventional treatment for IPMT is pancreatoduodenectomy. Some authors have advocated limited pancreatectomy for low-grade IPMTs of the pancreas, thereby decreasing the morbidity of more extensive resection. In this report, we describe our technique of minimal pancreatectomy, whereby the uncinate process and associated branch duct were completely extirpated while preserving remainder of the pancreatic head, duodenum, and pancreatic ducts. The case presented underscores the feasibility and advantages of minimal pancreatic resection in the management of such tumors.
Changes in the Allergenicity during Different Preparations of Pomfret, Hilsa, Bhetki and Mackerel Fish as Illustrated by Enzyme-Linked Immunosorbent Assay and Immunoblotting
Authors: Chatterjee U. , Mondal G. , Chakraborti P. , Patra H.K. , Chatterjee B.P.
Published: June 2006

Background: Although the identification and characterization of several fish allergens have already been reported, there is almost no data on Indian fish allergens and the effect of thermal processing on their allergenicity. This study aimed at the evaluation of the changes in the level of allergenicity of 4 highly consumed Indian fishes, i.e. pomfret, hilsa, bhetki and mackerel, that occurred after boiling and frying. Methods: In this study 110 patients with fish hypersensitivity as evidenced by clinical history and symptoms were recruited based on their positive skin prick test results. The raw, boiled and fried muscle extracts of the 4 fishes were prepared, and each extract was tested by ELISA and immunoblotting with patients’ sera. Results: ELISA and immunoblotting studies demonstrated that the raw muscle extracts of pomfret, hilsa, bhetki and mackerel were allergenic. While the allergenicity of boiled and fried extracts of pomfret and hilsa was considerably reduced, maximum allergenicity of bhetki was demonstrated in the fried extract. The degree of allergenicity of bhetki was demonstrated in the order fried > boiled > raw while that of mackerel followed the order raw > boiled ≃ fried. Conclusion: The specificIgE-binding activity and immunoblot profile clearly showed that pomfret and hilsa fish allergens are heat-labile, while allergens of bhetki and mackerel maintained strong reactivity even after thermal treatment.
A Natural Antibody to Oxidized Cardiolipin Binds to Oxidized Low-Density Lipoprotein, Apoptotic Cells, and Atherosclerotic Lesions
Authors: Tuominen Anu , Miller Yury I. , Hansen Lotte F. , Kesäniemi Y. Antero , Witztum Joseph L. , Hörkkö Sohvi
Published: June 2006

Objective—Cardiolipin (CL) is found in membranes of bacteria, in the inner membrane of mitochondria and in plasma low-density lipoprotein (LDL). Anticardiolipin antibodies (aCL) are associated with disease states, and we have suggested that many aCL bind to oxidized CL (oxCL) but not native CL. To determine the immunogenicity and origins of oxCL in vivo, we cloned a natural antibody to oxCL.

Methods and Results—A monoclonal IgM antibody to oxCL (LRO1) was cloned from a nonimmunized LDLR−/−mouse. The VHsequence originated from the VHGam3.8 germline with one nucleotide difference, and the Vκ was 100% identical to Vκ19–20 germline gene, making LRO1 a natural antibody. LRO1 bound specifically to oxCL and oxidized-LDL, but not to native CL or native LDL. LRO1 epitopes were demonstrated in apoptotic, but not in viable, Jurkat cells by flow cytometry, immunofluorescence and deconvolution microscopy. Human and rabbit atherosclerotic lesions contained LRO1 epitopes. Human LDL (n=113) showed LRO1 immunoreactivity, which correlated with aCL IgG titers (r=0.32,P=0.0004).

Conclusions—These data demonstrate that some aCL antibodies are highly conserved natural antibodies binding to oxCL in oxLDL, apoptotic cells, and atherosclerotic lesions. This suggests that oxCL is one of the pathogen-associated molecular patterns of innate immunity and gives insight into the pathogenic events of diseases with increased titers of aCL antibodies.