bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential regulation of TGF-β signal in hepatic stellate cells between acute and chronic rat liver injury
Authors: Tahashi Yoshiya , Matsuzaki Koichi , Date Masataka , Yoshida Katsunori , Furukawa Fukiko , Sugano Yasushi , Matsushita Masanori , Himeno Yasuo , Inagaki Yutaka , Inoue Kyoichi
Published: August 2002

During chronic liver injury, transforming growth factor β (TGF-β) plays a prominent role in stimulating liver fibrogenesis by myofibroblast-like cells derived from hepatic stellate cells (HSCs). On the other hand, Smad 7 was recently shown to antagonize the TGF-β-induced activation of signal-transducing Smads (2 and 3). In this study, we investigated the regulatory mechanisms of the TGF-β signals in rat HSCs during acute liver injury and myofibroblasts (MFBs) during chronic liver injury, focusing on the roles of Smad 2 and antagonistic Smad 7. In acute liver injury, HSC-derived TGF-β increased plasminogen activator inhibitor type 1 (PAI-1) and α2(I) procollagen (COL1A2) transcripts. Smad 2 in HSCs during liver injury and primary cultured HSCs were activated by an autocrine mechanism, because high levels of Smad 2 phosphorylation and induction of PAI-1 transcript by TGF-β were observed in HSCs. Thereafter, Smad 7 induced by TGF-β negatively regulated the Smad 2 action. These results indicated that endogenous TGFβ-mediated Smad 7 in HSCs terminated the fibrotic signals mediated by signal-transducing Smads, and might be involved in the transient response to autocrine TGF-β signal after acute liver injury. By contrast, Smad 7 was not induced by the autocrine TGF-β signal, and constitutive Smad 2 activation was observed in MFBs throughout chronic liver injury, although Smad 7 could inhibit the TGF-β signal requiring Smad 2 phosphorylation by activated TGF-β receptor in cultured MFBs. This constitutive phosphorylation of Smad 2 by endogenous TGF-β under a low level of Smad 7 could be involved in the progression of liver fibrosis.
Inhibition of internal ribosomal entry site-directed translation of HCV by recombinant IFN-α correlates with a reduced La protein
Authors: Shimazaki Takeo , Honda Masao , Kaneko Shuichi , Kobayashi Kenichi
Published: August 2002

Translation of the hepatitis C virus (HCV) polyprotein is mediated by an internal ribosome entry site (IRES) that is located within the 5′-nontranslated region (5′NTR). We investigated the effect of interferon alfa (IFN-α) on the IRES-directed translation of HCV, using two stably transformed cell lines, RCF-1 and RCF-26, of Huh7 cells derived from human hepatocellular carcinoma that express dicistronic reporter proteins, Renilla luciferase (RL) and firefly luciferase (FL), separated by HCV-IRES. After the administration of IFN-α or poly(I)-poly(C), HCV-IRES-directed translation was inhibited in a dose-dependent manner. The relative HCV-IRES activity (F/L) decreased to 60% at 5,000 IU/mL of IFN-α and 45% at 40 μg/mL of poly(I)-poly(C). Thus, IFN-α or poly(I)-poly(C) inhibited HCV-IRES-directed translation more efficiently than a cellular cap-dependent translation. 2′,5′-oligoadenylate synthetase (2′,5′AS) protein level in cells analyzed significantly increased after the administration of IFN-α, but not upon poly(I)-poly(C). Overexpression of double-stranded RNA-activated protein kinase (PKR) gene did not mimic the selective inhibition of HCV-IRES-directed translation in the transformant cells, suggesting that neither the 2′,5′AS nor the PKR system are involved in this selective inhibition. Interestingly, the expression of the autoantigen, La, which has been reported to enhance HCV-IRES-directed translation, was significantly reduced after the administration of IFN-α and poly(I)-poly(C) in a dose-dependent manner. Transient expression of La protein completely restored the selective inhibition of HCV-IRES-directed translation by IFN-α and poly(I)-poly(C). These findings suggested a new antiviral mechanism induced by IFN-α in that IFN-α or poly(I)-poly(C) selectively inhibited HCV-IRES-directed translation compared with the eukaryotic cap-dependent translation through the reduction of La protein.
Protection against acetaminophen-induced liver injury and lethality by interleukin 10: Role of inducible nitric oxide synthase
Authors: Bourdi Mohammed , Masubuchi Yasuhiro , Reilly Timothy P. , Amouzadeh Hamid R. , Martin Jackie L. , George John W. , Shah Anjali G. , Pohl Lance R.
Published: August 2002

Mechanistic study of idiosyncratic drug-induced hepatitis (DIH) continues to be a challenging problem because of the lack of animal models. The inability to produce this type of hepatotoxicity in animals, and its relative rarity in humans, may be linked to the production of anti-inflammatory factors that prevent drug-protein adducts from causing liver injury by immune and nonimmune mechanisms. We tested this hypothesis by using a model of acetaminophen (APAP)-induced liver injury in mice. After APAP treatment, a significant increase was observed in serum levels of interleukin (IL)-4, IL-10, and IL-13, cytokines that regulate inflammatory mediator production and cell-mediated autoimmunity. When IL-10 knockout (KO) mice were treated with APAP, most of these mice died within 24 to 48 hours from liver injury. This increased susceptibility to APAP-induced liver injury appeared to correlate with an elevated expression of liver proinflammatory cytokines, tumor necrosis factor (TNF)-α, and IL-1, as well as inducible nitric oxide synthase (iNOS). In this regard, mice lacking both IL-10 and iNOS genes were protected from APAP-induced liver injury and lethality when compared with IL-10 KO mice. All strains, including wild-type animals, generated similar amounts of liver APAP-protein adducts, indicating that the increased susceptibility of IL-10 KO mice to APAP hepatotoxicity was not caused by an enhanced formation of APAP-protein adducts. In conclusion, these findings suggest that an important feature of the normal response to drug-induced liver injury may be the increased expression of anti-inflammatory factors such as IL-10. Certain polymorphisms of these factors may have a role in determining the susceptibility of individuals to idiosyncratic DIH.
Activation of eNOS in rat portal hypertensive gastric mucosa is mediated by TNF-α via the PI 3-kinase-Akt signaling pathway
Authors: Kawanaka Hirofumi , Jones Michael K. , Szabo Imre L. , Baatar Dolgor , Pai Rama , Tsugawa Kouji , Sugimachi Keizo , Sarfeh James I. , Tarnawski Andrzej S.
Published: August 2002

Activation of endothelial nitric oxide synthase (eNOS) in portal hypertensive (PHT) gastric mucosa leads to hyperdynamic circulation and increased susceptibility to injury. However, the signaling mechanisms for eNOS activation in PHT gastric mucosa and the role of TNF-α in this signaling remain unknown. In PHT gastric mucosa we studied (1) eNOS phosphorylation (at serine 1177) required for its activation; (2) association of the phosphatidylinositol 3-kinase (PI 3-kinase), and its downstream effector Akt, with eNOS; and, (3) whether TNF-α neutralization affects eNOS phosphorylation and PI 3-kinase-Akt activation. To determine human relevance, we used human microvascular endothelial cells to examine directly whether TNF-α stimulates eNOS phosphorylation via PI 3-kinase. PHT gastric mucosa has significantly increased (1) eNOS phosphorylation at serine 1177 by 90% (P < .01); (2) membrane translocation (P < .05) and phosphorylation (P < .05) of p85 (regulatory subunit of PI 3-kinase) by 61% and 85%, respectively; (3) phosphorylation (P < .01) and activity (P < .01) of Akt by 40% and 52%, respectively; and (4) binding of Akt to eNOS by as much as 410% (P < .001). Neutralizing anti-TNF-α antibody significantly reduced p85 phosphorylation, phosphorylation and activity of Akt, and eNOS phosphorylation in PHT gastric mucosa to normal levels. Furthermore, TNF-α stimulated eNOS phosphorylation in human microvascular endothelial cells. In conclusion, these findings show that in PHT gastric mucosa, TNF-α stimulates eNOS phosphorylation at serine 1177 (required for its activation) via the PI 3-kinase-Akt signal transduction pathway.
Recombinant factor VIIa improves clot formation but not fibrolytic potential in patients with cirrhosis and during liver transplantation
Authors: Lisman Ton , Leebeek Frank W.G. , Meijer Karina , Van Der Meer Jan , Nieuwenhuis Karel H. , De Groot Philip G.
Published: August 2002

Cirrhosis is associated with a bleeding tendency, which is particularly pronounced during orthotopic liver transplantation (OLT). A novel approach to treating the bleeding diathesis of patients with cirrhosis is administration of recombinant factor VIIa (rFVIIa). This study examined whether the efficacy of rFVIIa in cirrhosis might be explained in part by enhanced down-regulation of fibrinolysis by thrombin-activatable fibrinolysis inhibitor (TAFI). Addition of therapeutic or supratherapeutic doses of rFVIIa to plasma of 12 patients with stable cirrhosis did not result in a prolongation of clot lysis time, though clotting times were significantly reduced. Also, clot lysis assays of plasma samples taken during and after OLT, which was performed with or without a single bolus dose of rFVIIa, did not show any effect of rFVIIa on plasma fibrinolytic potential. In conclusion, this study shows no evidence for an antifibrinolytic effect of rFVIIa in cirrhotic patients or in patients undergoing OLT.
The cyclooxygenase system participates in functional mdr1b overexpression in primary rat hepatocyte cultures
Authors: Ziemann Christina , Schäfer Dirk , Rüdell Gudrun , Kahl Georg F. , Hirsch-Ernst Karen I.
Published: August 2002

Overexpression of mdr1-type P-glycoproteins (P-gps) is thought to contribute to primary chemotherapy resistance of untreated hepatocellular carcinoma. However, mechanisms of endogenous multidrug resistance 1 (mdr1) gene activation still remain unclear. Because recent studies have demonstrated overexpression of cyclooxygenase-2 (COX-2) in hepatocytes during early stages of hepatocarcinogenesis, we investigated whether the COX system, which catalyzes the rate-limiting step in prostaglandin synthesis, participates in mdr1 gene regulation. In the present study, primary rat hepatocyte cultures, exhibiting time-dependent mdr1b overexpression, demonstrated basal COX-2 and COX-1 mRNA expression and liberation of prostaglandin E2 (PGE2), indicative of an active COX-dependent arachidonic acid metabolism. PGE2 accumulation in culture supernatants was further enhanced by arachidonic acid (1μmol/L) and epidermal growth factor (EGF) (16 nmol/L). PGE2 and prostaglandin F2α (PGF2α) (3-6μg/mL), added directly to the culture medium, significantly up-regulated intrinsic mdr1b mRNA overexpression and mdr1-dependent transport activity. Up-regulation was maximal after 3 days of culture. Like prostaglandins, the COX substrate, arachidonic acid, also induced mdr1b gene expression. Apart from this, structurally different COX inhibitors (indomethacin, meloxicam, NS-398) mediated significant inhibition of time-dependent and EGF-induced mdr1b mRNA overexpression, resulting in enhanced intracellular accumulation of the mdr1 substrate, rhodamine 123 (Rho123). Thus, the present data support the conclusion that the release of prostaglandins through activation of the COX system participates in endogenous mdr1b gene regulation. COX-2 inhibition might constitute a new strategy to counteract primary mdr1-dependent chemotherapy resistance.
Role of mitochondrial permeability transition in diclofenac-induced hepatocyte injury in rats
Authors: Masubuchi Yasuhiro , Nakayama Shintaro , Horie Toshiharu
Published: August 2002

Hepatotoxicity of diclofenac has been known in experimental animals and humans but its mechanism has not been fully understood. The present study examined the role of mitochondrial permeability transition (MPT) in the pathogenesis of diclofenac-induced hepatocyte injury by using isolated mitochondria and primary culture hepatocytes from rats. Incubation of energized mitochondria with succinate in the presence of Ca2+ and diclofenac resulted in mitochondrial swelling, leakage of accumulated Ca2+, membrane depolarization, and oxidation of nicotinamide adenine dinucleotide phosphate and protein thiol. All of these phenomena were suppressed by coincubation of the mitochondria with cyclosporin A, a typical inhibitor of MPT, showing that diclofenac opened the MPT pore. It was also suggested that reactive oxygen species probably generated during mitochondrial respiration and/or voltage-dependent mechanism was involved in MPT, which are proposed as mechanisms of MPT by uncouplers of mitochondrial oxidative phosphorylation. Culture of hepatocytes for 24 hours with diclofenac caused a decrease in cellular ATP, leakage of lactate dehydrogenase and membrane depolarization. The hepatocyte toxicity thus observed was attenuated by coincubation of the hepatocytes with cyclosporin A and verapamil, a Ca2+ channel blocker. In conclusion, these results showed the important role of MPT in pathogenesis of hepatocyte injury induced by diclofenac and its possible contribution to human idiosyncratic hepatotoxicity.
Ureteral Obstruction After Ureteroneocystostomy in Dogs Assessed by Technetium Tc 99m Diethylenetriamine Pentaacetic Acid (DTPA) Scintigraphy
Authors: Barthez Paul Y. , Smeak Daniel D. , Wisner Erik R. , Dibartola Stephen P. , Chew Dennis J.
Published: August 2002

Objective—To use technetium Tc 99m diethylenetriamine pentaacetic acid (99mTc‐DTPA) renal scintigraphy to monitor ureteral obstruction after ureteroneocystostomy in a canine model of partial ureteral obstruction.

Study Design—Experimental study.

Animals—Eight normal adult dogs.

Methods—Partial ureteral obstruction was created in 8 dogs by incomplete ligation of the terminal right ureter. Two weeks later, ureteroneocystostomy was performed in 7 dogs with unilateral partial ureteral obstruction and in 1 dog that had developed bilateral partial ureteral obstruction.99mTc‐DTPA scintigraphy was performed intermittently for 2 weeks after ureteroneocystostomy. Renal transit time of each kidney, as assessed by the time to maximal uptake (time of peak), and glomerular filtration rate, as assessed by percentage of kidney uptake of the radiopharmaceutical between 1 and 3 minutes, were estimated. Comparison between affected and nonaffected kidneys was performed with the Wilcoxon rank sum test.

Results—Unilateral partial ureteral obstruction was induced successfully in 7 dogs. In 1 dog, bilateral partial obstruction was induced inadvertently. After ureteroneocystostomy, percentage of kidney uptake of99mTc‐DTPA was low in 4 affected kidneys. The uptake returned to within normal limits in 2 of the kidneys during the observation period. The time activity curve had a more rounded appearance or was increasing continuously for all affected kidneys. A significant increase in renal transit time was observed 2 and 4 days after ureteroneocystostomy. Transit time progressively returned to normal by 4 to 11 days for all affected kidneys except 1.

Conclusion—Ureteroneocystostomy resulted in persistent partial ureteral obstruction for 4 to 11 days as determined by99mTc‐DTPA scintigraphy.

Clinical Relevance—99mTc‐DTPA scintigraphy may be a useful procedure for monitoring renal function and ureteral obstruction after ureteroneocystostomy. Persistent partial ureteral obstruction may be seen 1 to 2 weeks after ureteral reimplantation in dogs with previously existing dilated ureters.
An In Vitro Comparison of Cordopexy, Cordopexy and Laryngoplasty, and Laryngoplasty for Treatment of Equine Laryngeal Hemiplegia
Authors: Jansson Nicolai , Ducharme Norm G. , Hackett Richard P. , Mohammed Hussni O.
Published: August 2002

Objective—To examine the effect of cordopexy, laryngoplasty, and cordopexy combined with a modified laryngoplasty on airway mechanics.

Study Design—Experimental airway mechanics were determined by subjecting equine cadaveric larynges to airflows similar to inspiratory airflow of exercising horses.

Animals or Sample Population—Twenty equine larynges.

Methods—Using cadaveric larynges, we developed and tested a new technique of arytenoid cartilage abduction. All larynges had the right arytenoid cartilage abducted to mimic the degree of arytenoid abduction that occurs at maximal exertion in live horses. Three surgical techniques were used to stabilize the left arytenoid cartilage of treated larynges; the left arytenoid cartilage was not stabilized in control larynges. Technique 1: Cordopexy—a suture was placed between the vocal ligament and the lamina of the thyroid cartilage. Technique 2: Standard laryngoplasty—a suture was placed between the muscular process of the arytenoid cartilage and the caudomedial aspect of the cricoid cartilage. Technique 3: Cordopexy plus modified laryngoplasty—the cordopexy suture was placed with a second suture between the horizontal ridge rostral to the muscular process of the left arytenoid cartilage and the lamina of the thyroid cartilage. Translaryngeal impedances (TI) were determined for each surgical technique by subjecting the larynges to increasing airflows and measuring the translaryngeal pressure differences. The arytenoid right to left angle quotient (RLQ) and the glottic cross‐sectional area (CSA) were also measured.

Results—At maximal airflow, the adjusted means for the arytenoid RLQ and the TI for the cordopexy plus modified laryngoplasty (1.48 ± 0.04, 0.69 ± 0.05 cm H2O/L/s) and the standard laryngoplasty (1.39 ± 0.04, 0.78 cm H2O/L/s,) were different (P< .05) from values obtained after cordopexy alone (2.74 ± 0.37, 1.76 ± 0.48 cm H2O/L/s) or in control larynges (3.66 ± 0.54, 4.16 ± 0.96 cm H2O/L/s). Overall, a cordopexy plus modified laryngoplasty (9.69 cm2), a standard laryngoplasty (9.34 cm2), and a cordopexy alone (9 cm2) resulted in an increased glottic CSA greater than that for control larynges (6.94 cm2;P= .0001).

Conclusions—Cordopexy alone did not improve airflow in a left laryngeal hemiplegic model. Cordopexy plus modified laryngoplasty was as efficacious as the standard laryngoplasty in alleviating the effects of left laryngeal hemiplegia on TI, glottic CSA, and arytenoid RLQ.

Clinical Relevance—Fixation of the vocal cord (cordopexy) in addition to a laryngoplasty procedure may prove useful in the surgical treatment of equine laryngeal hemiplegia.
The Effect of Implanting Gentamicin‐Impregnated Polymethylmethacrylate Beads in the Tarsocrural Joint of the Horse
Authors: Farnsworth Kelly D. , White Nathaniel A. , Robertson John
Published: August 2002

Objective—To determine the effect of intra‐articular gentamicin‐impregnated polymethylmethacrylate (PMMA) beads inserted in the equine tarsocrural joint on the synovial fluid, synovial lining, and cartilage, and to determine the peak and sustainable gentamicin concentrations in synovial fluid and plasma.

Study Design—Pharmacokinetic, cytologic, and histologic study of the effect of gentamicin‐impregnated PMMA on normal equine tarsocrural joints.

Animals—Five healthy adult horses.

Methods—Gentamicin‐impregnated PMMA bead strands (3 strands each of 40 beads, with each strand containing 100 mg gentamicin) were surgically inserted into one radiographically normal tarsocrural joint in 5 horses. Each horse had both joints flushed with 1 L of lactated Ringer's solution before bead administration. Synovial fluid total protein concentration, white blood cell (WBC) count, gentamicin concentration, synovial histology, cartilage integrity, and cartilage glycosaminoglycan (GAG) concentrations were determined.

Results—Gentamicin concentration (mean ± SEM peak concentration, 27.9 ± 2.27 μg/mL) occurred in the first 24 hours and remained above 2 μg/mL for 9 days. Gentamicin concentrations in control joints and the plasma remained below detectable levels. The synovial fluid WBC count for treated joints was increased compared with control joints for 72 hours, but was similar at day 6. The synovial protein concentration in gentamicin‐treated joints remained increased for 21 days. Synovium in treated joints had diffuse synovitis, whereas control joints had less fibrovascular proliferation. Superficial cartilage erosion was present in all treated joints. There was no difference in the GAG content of treated and control joint cartilage.

Conclusions—Short‐term implantation of gentamicin (300 mg)‐impregnated PMMA beads can provide therapeutic levels of gentamicin (>2 μg/mL) in the normal tarsocrural joint for 9 days; however, gentamicin‐impregnated PMMA beads induce synovitis and superficial cartilage erosion.

Clinical Relevance—Temporary intra‐articular administration of antibiotic‐impregnated PMMA may be an effective way to treat septic joints that require constant high concentrations of antibiotics.
Podotrochlear Bursa Endoscopy in the Horse: A Cadaver Study
Authors: Cruz Antonio M. , Pharr John W. , Bailey Jeremy V. , Barber Spencer M. , Fretz Peter B.
Published: August 2002

Objectives—To evaluate podotrochlear bursa (navicular bursa) endoscopy as a diagnostic technique in horses and to correlate observations to radiographic and pathologic findings.

Study Design—Descriptive study.

Sample Population—Seventeen equine cadaver forelimbs.

Methods—Five standard radiographic views of the navicular region and a bursographic study with lateromedial and caudal tangential radiographic views were taken of each forelimb. Radiographic scoring of the navicular bone (0, excellent; 1, good; 2, fair; 3, poor) was performed using a previously reported technique. Endoscopic examination was performed using a 30° wide‐angle forward oblique–viewing, 4‐mm outside diameter (OD), arthroscope. Four examiners using recorded videotapes made independent evaluations of bursal endoscopy. The specimens were then dissected and examined to verify radiographic and endoscopic findings.

Results—The distribution of radiographic scores (RS) were 0 (5 limbs), 1 (7), 2 (2), and 3 (3). Abnormal endoscopic findings (fibrillation of the deep digital flexor tendon, a defect in the navicular bone fibrocartilage, and synovial hyperplasia) were identified in 3 limbs (2 with an RS of 1, and 1 with an RS of 3). The endoscopic observations made in the two RS 1 bursae were not confirmed on gross examination, whereas they were in the RS 3 specimen, which also had the only abnormal bursogram. Evaluation of the bursa on the side ipsilateral to the arthroscope portal was difficult. Complications of the technique included inadvertent penetration of the distal interphalangeal joint and the digital sheath, and superficial scoring of the navicular bone fibrocartilage.

Conclusions—Podotrochlear bursa endoscopy is feasible and may be a useful technique in identifying early abnormalities associated with podotrochleosis.

Clinical Relevance—In horses with podotrochleosis, endoscopic examination of the podotrochlear bursa may improve identification of pathologic changes within the bursa.
An Evaluation of Two Autologous Tendon Grafting Techniques in Ponies
Authors: Reiners Scott R. , Jann Henry W. , Stein Larry E. , Good James K. , Claypool P. Larry
Published: August 2002

Objective—To compare the healing and mechanical strength of a multiple split autologous tendon graft (MG) to a whole autologous tendon graft (WG) in the deep digital flexor tendon of ponies.

Study design—In vitro evaluation of two different tendon‐grafting techniques.

Animals or sample population—Six ponies of mixed gender and age.

Methods—Tenotomies performed in forelimb deep digital flexor tendons (DDFT) distal to the insertion of the accessory ligament (AL‐DDFT) were repaired with free autologous grafts from the hindlimb lateral digital extensor tendon (LDET). Grafts were either whole (WG) or split into three longitudinal strips (multiple graft, MG). Tendons and graft sites were collected and loaded (2.54 cm/s) to failure at either 4 or 8 weeks after surgery. Cross‐sectional area was determined by both impression cast (IC) and an inkblot (IB) method. Tissue maturity and inflammation were evaluated by microscopy.

Results—Gap formation was a consistent finding in all repair sites. No statistical differences were found in healing or mechanical variables between MG and WG techniques. The failure stress for the 8‐week repairs (15.51 ± 3.1 MPa IB and 11.73 ± .77 MPa IC, 16.13 ± 2.2 MPa IB and 10.22 ± .76 MPa IC for MG and WG, respectively) were significantly greater (P< .0005) than for 4‐week repairs (3.71 ± 1.7 MPa IB and 2.68 ± 1.44 MPa IC, 2.81 ± 1.46 MPa IB and 2.3 ± 1.7 MPa IC for MG and WG, respectively). The repair tissue was more mature (P< .05) at 8 weeks than at 4 weeks, but there was no significant difference in inflammatory responses at 4 and 8 weeks.

Conclusions—There was a sixfold increase in strength between 4 and 8 weeks of healing, but no significant difference in healing or strength between the MG and WG techniques.

Clinical relevance—In ponies, autologous tendon grafting contributes to a strong repair during the early convalescent period, but splitting a tendon graft seemingly offers no appreciable advantage over use of a whole graft.
Epidural Morphine and Detomidine Decreases Postoperative Hindlimb Lameness in Horses after Bilateral Stifle Arthroscopy
Authors: Goodrich Laurie R. , Nixon Alan J. , Fubini Susan L. , Ducharme Norm G. , Fortier Lisa A. , Warnick Lorin D. , Ludders John W.
Published: August 2002

Objective—To determine whether preoperative epidural administration of morphine and detomidine would decrease postoperative lameness after bilateral stifle arthroscopy in horses.

Study design—Prospective clinical controlled study.

Animals—Eight adult horses that had bilateral arthroscopic procedures, including drilling of cartilage and subchondral bone within the femoropatellar joints.

Methods—Horses were randomly separated into 2 groups. Preoperatively, 4 horses were administered a combination of epidural morphine (0.2 mg/kg) and detomidine (30 μg/kg), and 4 horses were administered an equivalent volume of epidural saline (0.9% NaCl) solution. Postoperative pain was assessed using 6 video recordings made at hourly intervals of each horse at a walk. Assessments began 1 hour after recovery from anesthesia. The recordings were scrambled out of sequence and evaluated by 3 observers, unaware of treatment groups, who scored lameness from 0 to 4. Lameness scores of the 2 groups of horses were compared using a Wilcoxon's rank sum test. Heart and respiratory rates were also measured at each hourly interval and compared between groups using a repeated‐measures ANOVA; statistical significance was set atP< .05.

Results—Preoperative administration of epidural morphine and detomidine significantly decreased lameness and heart rates after bilateral stifle arthroscopy. The greatest decrease was detected at hours 1 and 2 after recovery from anesthesia.

Conclusion—We conclude that horses undergoing a painful arthroscopic procedure of the stifle joint benefit from the administration of preoperative epidural morphine and detomidine.

Clinical relevance—Preoperative epidural administration of detomidine and morphine may be useful in decreasing postoperative pain after stifle arthroscopy as well as pain associated with other painful disorders involving the stifle joint, such as septic arthritis and trauma.
The Effect of Equine Recombinant Growth Hormone on Second Intention Wound Healing in Horses
Authors: Dart Andrew J. , Cries Lucile , Jeffcott Leo B. , Hodgson David R. , Rose Reuben J.
Published: August 2002

Objective—To evaluate the effect of intramuscular administration of recombinant equine growth hormone on healing of full thickness skin wounds on equine limbs.

Study design—Experimental.

Animals—Nine Standardbred horses.

Methods—In study 1, standardized full thickness skin wounds (2.5 × 2.5 cm) were made over the dorsomedial aspect of the mid‐cannon bone of 1 forelimb and 1 hindlimb in 9 horses. Wounds were bandaged without treatment (control subjects) and videorecorded twice weekly until healed. Then, in study 2, similar wounds were created on the opposite limbs; 6 horses were administered intramuscular recombinant equine growth hormone (10 μg/kg daily for 7 days, then 20 μg/kg daily for 49 days), and 3 horses (control subjects) were administered equivalent volumes of sterile water. Wounds were videorecorded twice weekly until healed. Wound healing variables were measured from the videorecordings using a computer software package and analyzed as a randomized complete block design factorial analysis of variance; significance was set atP< .05.

Results—No differences in the measured variables were detected between wounds in study 1 and the control wounds in study 2. In recombinant equine growth hormone–treated horses, wounds retracted more during treatment and contracted faster after treatment stopped when compared with wounds from untreated horses. No other treatment effects were detected.

Conclusions—Recombinant equine growth hormone seemingly increases wound retraction. After treatment ceases, wound contraction increases.

Clinical relevance—Intramuscular administration of recombinant equine growth hormone (10 μg/kg daily for 7 days, then 20 μg/kg daily for 49 days) does not appear to have any beneficial clinical effect on healing of equine limb wounds.
Are Circular External Fixators Weakened by the use of Hemispheric Washers?
Authors: Marcellin‐Little Denis J. , Roe Simon C. , Rovesti Gian Luca , Bosio Alessandro , Ferretti Antonio
Published: August 2002

Objectives—To compare the axial mechanical stability of 3 circular external fixators systems with and without hemispheric washers.

Study design—Experimental study.

Methods—The axial stiffness and load necessary to produce 0.5 and 1 mm of displacement of 10 circular external fixator constructs from 3 manufacturers were tested on a materials testing machine. The constructs tested included the Small Bone fixator (SBF; Hofmann S.a.S., Monza, Italy), the IMEX ring fixator (IMEX Inc., Longview, TX), and the Multiplanar C‐Fix (MCF; PanVet Distribuzione, Seriate, Italy). Five configurations were tested for each construct: (1) conventional nut fixation, (2) hemispheric washer fixation with connecting rods offset by 0, (3) 1, and (4) 2 holes, and (5) with a ring placed at maximum angulation.

Results—The loads resisted at 0.5 and 1 mm of displacement did not differ when frame configurations were compared (P=.25733 and .33769, respectively). The linear stiffness of the following configurations were decreasingly stiff: standard constructs, hemispheric washers with connecting rods perpendicular to rings, hemispheric washers with connecting rods offset by 1 hole, hemispheric washers with connecting rods offset by 2 holes, and ring offset in relation to bone model. The SBF constructs tested were 34% and 41% more rigid than the IMEX and MCF constructs tested despite the larger diameter of the connecting rods for the IMEX frames (6 mm) compared with the SBF frames (5 mm). The IMEX constructs tested were 6% more rigid than the MCF constructs tested.

Conclusions—Adding hemispheric washers and angling connecting rods in relation to rings did not influence the loads resisted at 0.5 and 1 mm displacement but decreased construct stiffness.

Clinical relevance—The use of hemispheric washers had minor effects on the biomechanical performance of fixator frames tested in this study when used to angle a ring in relation to connecting rods for circular external fixators.
The meaning of `public understanding of science' in the United States after World War II
Authors: Lewenstein Bruce V.
Published: August 2002

In the United States after World War II, the term `public understanding of science' became equated with `public appreciation of the benefits that science provides to society'. This equation was the result of the independent, but parallel, social and institutional needs of four different groups with an interest in popularizing science: commercial publishers, scientific societies, science journalists, and government agencies. A new, more critical era of popular science began in the 1960s.
Science on display: the representation of scientific controversy in museum exhibitions
Authors: Macdonald Sharon , Silverstone Roger
Published: August 2002

This article raises issues concerning popular representations of science, and in particular of scientific controversy, through a case-study of the treatment of food poisoning controversy in a museum exhibition. It is argued that the science that is created for the public is shaped not only by the overt intentions of the exhibition makers but also by constraints inherent in structural aspects of the exhibition-making process and exhibition philosophies. More specifically, we argue that some of the strategies intended to foster public understanding of science create problems for the representation of scientific controversy, and, more generally, for certain types of science. The article also gives attention to scientific sources and the politics of the museum's relationship with the scientific community and the food industry. The contrast with other media is made throughout the article as a means of highlighting the different strategies employed, and constraints experienced, by the various institutions involved in putting science on display for the public.
Mass media coverage of technological and environmental risks: a survey of research in the United States and Germany
Authors: Dunwoody Sharon , Peters Hans Peter
Published: August 2002

Research on media communication of risks has become a reasonably well funded and popular domain for scholars around the world. Although one can find a great deal of collaboration among these scholars within countries, cross-cultural collaborations are far more rare. In this article, an American and a German scholar attempt to bring results from studies in both their countries to bear on some of the more popular questions being asked by risk communication researchers and practitioners. With a few exceptions, studies from the two countries demonstrate highly consonant results, suggesting great similarities between (1) the general social and technological cultures of these two developed countries, (2) the ways in which their scientific and journalistic cultures deal with the concept of risk, and (3) the ways in which risk communication researchers in these two countries conceptualize and operationalize this domain of inquiry. The review concentrates on studies that examine the construction of risk stories by journalists but offers a framework within which to examine story effects as well.
Science in magazines, and its readers
Authors: Jacobi Daniel , Schiele Bernard
Published: August 2002

How do magazines make science accessible and appealing to a broad readership? To answer this question, we studied an article which was published in Le Figaro magazine, the weekly magazine supplement of a large French daily newspaper. The article, which presents information on cancer and immunology, is illustrated with three large and spectacular colour photographs of microscopic corpuscles. A semio-linguistic and communications analysis revealed that a general series of elements, made up of headlines, photos and captions, forms a kind of narrative that can be read like a short melodrama. The text of the interview with the researcher proposes reformulations, directed to conscientious readers who take the trouble to understand the specialized terms. Finally, in the infratext, experts and specialists are able to discern references and allusions to different sorts of issues at play. In short, we show how an article can simultaneously attract different categories of readers.
Reading risk: public response to print media accounts of technological risk
Authors: Hornig Susanna
Published: August 2002

Two clearly defined positions on the evaluation of technological risks have emerged in the scholarly literature in a variety of disciplines: a `rationalist' perspective and a `subjectivist' perspective. This paper argues from a subjectivist position that differences between scientific and lay responses to risk information (as presented in media accounts) are not necessarily generally attributable to `misinterpretations' by nonscientific readers, and that the process through which lay publics interpret mass media accounts of risk is worthy of more study. Data are presented from twenty focus group discussions, involving 114 student respondents, of a range of print media articles about risky technologies. The results suggest that lay publics work with an `expanded vocabulary of risk' that takes into account a variety of issues having to do with information, implementation, regulation, and ethical considerations, as well as the cost and benefit factors traditionally weighed by risk assessors. The scientific community needs to recognize that the public expects this kind of broader accountability, and media accounts need to be written to respond to needs in these areas.
Life in the laboratory: public responses to experimental biology
Authors: Turney Jon
Published: August 2002

Present-day public attitudes to biological manipulation are ambivalent, many surveys show. This paper explores evidence of earlier attitudes to experimental biology, before survey data exists, by examining published responses in the press to the idea that biologists would `create life'. This remarkable claim achieved wide currency in the early years of this century, particularly linked to the work of two prototypical `visible scientists': Jacques Loeb and Alexis Carrel. Analysis of press responses to accounts of their work reveals deep disquiet about its possible implications, at a time when science and technology in general were regarded very positively. The evidence is augmented by studying commentary on a Presidential Address by Edward Schafer to the British Association meeting of 1912. It is concluded that feelings of ambivalence toward the manipulative power of biology are apparent at a very early stage in the development of modern biology, and that this makes it implausible that more recent manifestations of such ambivalence can be ascribed to some generalized `anti-science' sentiment which has gathered strength in recent years.
The development of young American adults' attitudes about the risks associated with nuclear power
Authors: Pifer Linda K.
Published: August 2002

Young American adults' assessment of the risks associated with nuclear power was examined by using data from the Longitudinal Study of American Youth (LSAY). A structural equation model was estimated using LISREL8 to examine the development of young adults' attitudes toward nuclear power. Many factors that have been associated with general attitudes toward science and technology were found to have no effect on young adults' assessment of the risks of nuclear power. Science achievement, academic science attitudes, and enrolment in high school and college science courses were found to have no effect on young adults' attitudes. Twelfth grade students who believed that the risks of nuclear power were relatively low were more likely to hold the same beliefs as young adults. Plans to have a career in science, mathematics, or engineering in grade twelve had the second greatest total effects, while gender's total effects were nearly identical in magnitude. Partisan identification had the fourth greatest total effects on attitudes about the risks of nuclear power. Peer science push, parent college push, parent science push, and parent education had lesser, but significant effects on the attitudes of young adults about the risks of nuclear power.
Science on TV: forms and reception of science programmes on French television
Authors: de Cheveigné Suzanne , Véron Eliséo
Published: August 2002

We report a study of the reception by adults of science programmes broadcast on French television. Long, semi-directive interviews were carried out during which a number of short fragments of the programmes were shown. This research, which is part of a wider study (including children, scientists and professionals involved in the production of such programmes), shows that there are not one but several, very different, readings of science programmes. That implies that, from the point of view of the public, there is no unique, `ideal' form for a science programme and that, indeed, the term `popularization of science' can have several very different meanings.
When science and the public meet: training for genetic counseling
Authors: da Rosa Vivian Leyser , Solomon Joan
Published: August 2002

Genetic counseling is beginning to be recognized as a very complex endeavor, as is its training. Attempts to list the separate purposes to be achieved, like the findings of research and evaluation of the process, have been unsatisfactory and even contradictory. These attempts are compared with somewhat similar results in quite different fields of the public understanding of science. The paper discusses these results in the context of first-year and post-graduate courses in human genetics given in a Brazilian university. We suggest that the students' reactions to genetic counseling may be better understood on a two domain model of knowing, and that an explicit understanding of this perspective might be of assistance to trainee genetic counselors while they are learning how to help clients more effectively.
How the public understands genetics: non-deterministic and non-discriminatory interpretations of the “blueprint” metaphor
Authors: Condit Celeste M.
Published: August 2002

Critics have worried that recent mass media coverage of genetics encourages genetic determinism and discriminatory attitudes in the public. They have identified the “blueprint” metaphor as one major component of public discourse that encourages such undesirable public opinions. To assess public interpretations of popular discourse about genetics, this audience study exposed 137 college students to sample genetics news articles and asked for their interpretations of the “blueprint” metaphor and of genetics in general. A larger group, the plurality, offered non-deterministic interpretations and perspectives on genetics. A small minority offered discriminatory interpretations, whereas a plurality offered explicit antidiscriminatory interpretations and opinions. Non-deterministic views were based on interpretations of the blueprint metaphor that understood genes as operating in a partial and probabilistic fashion, and that interpreted genes as malleable through individual will or technological intervention.
Genetic testing and the moral dynamics of family life
Authors: Juengst Eric T.
Published: August 2002

American families are a segment of the public that will feel the impact of the Human Genome Project most acutely: but they are also one of the least well studied segments with regard to that impact. Three sets of ethical problems, in particular, deserve more scrutiny: the effect of increased genetic risk assessment on family members' willingness to assist their kin discover mutually incriminating genetic risks, its impact on the candor with which extended families communicate within themselves about their genetic health risks, and its influence on the ways that families seek to protect the interests of their most vulnerable members. In each of these areas, anecdotal experience already shows how genetic testing can undermine a family's commitment to its own interdependence in these ways, and that traditional, multigenerational, sessile families are likely to experience more disruption than either blended families or “virtual families” linked primarily through electronic communication.
Laypeople's viewpoints about the reasons for expert controversy regarding food additives
Authors: Kajanne Anna , Pirttilä-Backman Anna-Maija
Published: August 2002

The focus in this study is on the thoughts and opinions of the general public to the divergence in expert standpoints regarding additives in food. The relation of education, length of work experience, occupational field, gender, and people's ideas on this matter, as well as the changes in it, were of interest. Fifty-nine young and middle-aged Finnish adults were interviewed during the years 1986-1988 and again in 1993-1994. The semi-structured interview included straightforward questions about reasons for disagreements among experts regarding additives; in other parts of the interview people could spontaneously comment on the discrepancies. Three main categories of reasons for the disagreement emerged. General difficulty in obtaining scientific knowledge was the most common reason given. In the second interview round, a greater number of less well-educated interviewees expressed views in this category. The second category was various interest-related reasons. The increase of these notions was statistically significant among the academics. The least common category concerned differences in the caliber and personal background of experts. Especially people with long experience in working life increased their notions in all three categories. The results showed that people are well aware of the many factors that may influence the acquisition of scientific knowledge, as well as its use. Moreover, the results showed that the more education people have the more aware they are of the various interests. Because laypeople have experiences and viewpoints about various open questions and risks, it is suggested here that their opinions should receive more attention in the public discussion of similar issues.
Creating (public) science in the Noah's Ark case
Authors: Edmond Gary , Mercer David
Published: August 2002

This paper explores how a recent “Creation Science” case from the Australian Federal Courts was used by an informal alliance of science popularizers (science litigant Ian Plimer, science journalists, and the Australian Skeptics) as a vehicle for the celebratory “boundary working” of “public science,” despite the case's contingent and messy processes and unfavourable legal outcome. This “boundary working” was pursued mainly through the mass media, in which a narrow range of narrative strategies involving well-worn metaphors and clichés conforming to the ideology of science dominated the case's coverage. The dominance of these narratives resulted in a marginalized coverage of the legal/policy ramifications of the case, particularly the role of the courts in preserving/limiting freedom of speech. We will conclude our analysis by identifying some similarities between the Ark case and the Science Wars, nothing that both instances show how the “boundary working” of “public science” can be pursued in a cultural space located at a significant distance from contexts where more tangible science policies are being negotiated.
An overview of science and technology coverage in Indian English-language dailies
Authors: Dutt Bharvi , Garg K. C.
Published: August 2002

News items on science and technology in English-language newspapers published in different parts of India during January-December 1996 were analyzed. Results indicate that the greatest proportion of newspaper space was devoted to nuclear science and technology, followed by defense, space research, and astronomy. The Pioneer, The Hindu, and The Times of India were the newspapers that together devoted about 23 percent of the total space to items on science and technology. The sources for most of the articles (97 percent) on policy issues originated from within India, while for other stories foreign sources, including those from the United States and the United Kingdom, also contributed. Many of the items were supported by illustrations such as photographs and diagrams. The study indicates that, on average, Indian newspapers devoted far less than one percent of the total printed space to articles and stories related to science and technology.