bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibitory effect of probiotic Escherichia coli strain Nissle 1917 on adhesion to and invasion of intestinal epithelial cells by adherent–invasive E. coli strains isolated from patients with Crohn's disease
Authors: Boudeau J. , Glasser A.‐L. , Julien S. , Colombel J.‐F. , Darfeuille‐Michaud A.
Published: July 2003

Background : Pathogenic adherent–invasive Escherichia coli have been isolated from ileal lesions of Crohn's disease.

Aim : To investigate the non‐pathogenic E. coli strain Nissle 1917 (Mutaflor) as possible maintenance therapy in inflammatory bowel disease by testing its ability to prevent adherent–invasive E. coli strains from adhering to and invading human intestinal epithelial cells in vitro.

Methods : Bacterial adhesion to and invasion of intestinal epithelial cells (Intestine‐407) were assessed by counting the colony‐forming units. The inhibitory effect of E. coli Nissle 1917 was determined after co‐incubation with adherent–invasive E. coli strains or after pre‐incubation of the intestinal epithelial cells with this probiotic strain prior to infection with adherent–invasive E. coli strains.

Results : Strain Nissle 1917 exhibited dose‐ and time‐dependent adherence to intestinal epithelial cells and inhibited the adhesion and invasion of various adherent–invasive E. coli strains. In co‐infection experiments, the inhibitory effect on adherent–invasive E. coli adhesion reached 78–99.9%. Pre‐incubation of intestinal epithelial cells with strain Nissle 1917 reduced adherent–invasive E. coli adhesion by 97.2–99.9%. The inhibitory effect on adherent–invasive E. coli invasion paralleled that on adhesion.

Conclusion : As strong and significant inhibitory effects on adherent–invasive E. coli adhesion and invasion were observed in co‐infection and pre‐infection experiments, E. coli Nissle 1917 could be efficient for preventive or curative probiotic therapy in patients with Crohn's disease.
Basiliximab (anti‐CD25) in combination with steroids may be an effective new treatment for steroid‐resistant ulcerative colitis
Authors: Creed T. J. , Norman M. R. , Probert C. S. J. , Harvey R. F. , Shaw I. S. , Smithson J. , Anderson J. , Moorghen M. , Gupta J. , Shepherd N. A. , Dayan C. M. , Hearing S. D.
Published: July 2003

Background : Steroid resistance represents a major clinical problem in the treatment of ulcerative colitis. In vitro, interleukin‐2 renders lymphocytes steroid resistant.

Aim : To explore the therapeutic potential of interleukin‐2 receptor blockade in steroid‐resistant ulcerative colitis with both in vitro measures and a pilot in vivo study.

Methods : Ten patients with steroid‐resistant ulcerative colitis received a single bolus of 40 mg of intravenous basiliximab plus steroid treatment in an open‐label, uncontrolled, 24‐week study. The outcome was assessed using the Ulcerative Colitis Symptom Score, rectal biopsy and Inflammatory Bowel Disease Questionnaire. Lymphocyte steroid sensitivity was measured in vitro in 39 subjects in the presence or absence of basiliximab.

Results : Nine of the 10 patients achieved clinical remission within 8 weeks. At 24 weeks, seven patients were in clinical remission. Marked improvement in the Ulcerative Colitis Symptom Score was seen by 1 week (P = 0.004) and on rectal biopsy and Inflammatory Bowel Disease Questionnaire by 2 weeks (both P < 0.05). Improvements persisted to 24 weeks (Ulcerative Colitis Symptom Score, Inflammatory Bowel Disease Questionnaire, both P < 0.005). Eight of the nine responders relapsed (median, 9 weeks), but remission was re‐achieved with further corticosteroids and the addition of azathioprine. At 24 weeks, seven patients were in full clinical remission, five off all steroid therapy. In vitro measurement of lymphocyte steroid sensitivity demonstrated steroid resistance in 22% of subjects. All were rendered steroid sensitive in the presence of basiliximab.

Conclusions : Basiliximab appears to be effective at inducing remission in steroid‐resistant ulcerative colitis. In vitro, basiliximab also produced a dramatic increase in lymphocyte steroid sensitivity in healthy subjects. Confirmation in randomized controlled studies is required.
Randomized, double‐blind, placebo‐controlled trial of prednisolone in post‐infectious irritable bowel syndrome
Authors: Dunlop S. P. , Jenkins D. , Neal K. R. , Naesdal J. , Borgaonker M. , Collins S. M. , Spiller R. C.
Published: July 2003

Background : Post‐infectious irritable bowel syndrome is associated with increased serotonin‐containing enterochromaffin cells and lymphocytes in rectal biopsies. Animal studies have suggested that steroids reduce the lymphocyte response and suppress some of the post‐infectious changes in neuromuscular function.

Aim : To evaluate whether steroids reduce the number of enterochromaffin cells and improve the symptoms of post‐infectious irritable bowel syndrome.

Methods : Twenty‐nine patients with post‐infectious irritable bowel syndrome underwent a randomized, double‐blind, placebo‐controlled trial of 3 weeks of oral prednisolone, 30 mg/day. Mucosal enterochromaffin cells, T lymphocytes and mast cells were assessed in rectal biopsies before and after treatment, and bowel symptoms were recorded in a daily diary.

Results: Initial enterochromaffin cell counts were increased and correlated with initial lamina propria T‐lymphocyte counts (r = 0.460, P = 0.014). Enterochromaffin cell counts did not change significantly after either prednisolone (− 0.8% ± 9.2%) or placebo (7.9% ± 7.9%) (P = 0.5). Although lamina propria T‐lymphocyte counts decreased significantly after prednisolone (22.0% ± 5.6%, P = 0.003), but not after placebo (11.5% ± 8.6%, P = 0.1), this was not associated with any significant treatment‐related improvement in abdominal pain, diarrhoea, frequency or urgency.

Conclusions : Prednisolone does not appear to reduce the number of enterochromaffin cells or cause an improvement in symptoms in post‐infectious irritable bowel syndrome. Other approaches to this persistent condition are indicated.
Mitogen‐activated protein kinases in chronic intestinal inflammation — targeting ancient pathways to treat modern diseases
Authors: Waetzig G. H. , Schreiber S.
Published: July 2003

Conventional treatment of chronic inflammatory disorders, including inflammatory bowel diseases, employs broad‐range anti‐inflammatory drugs. In order to reduce the side‐effects and increase the efficacy of treatment, several strategies have been developed in the last decade to interfere with intercellular and intracellular inflammatory signalling processes. The highly conserved mitogen‐activated protein kinase pathways regulate most cellular processes, particularly defence mechanisms such as stress reactions and inflammation. In this review, we provide an overview of the current knowledge of the specificity and interconnection of mitogen‐activated protein kinase pathways, their functions in the gut immune system and published and ongoing studies on the role of mitogen‐activated protein kinases in inflammatory bowel disease. The development of mitogen‐activated protein kinase inhibitors and their use for the therapy of inflammatory disorders is a paradigm of the successful bridging of the gap between basic research and clinical practice.
Heartburn severity can predict pathologic oesophageal reflux in gastro‐oesophageal reflux disease patients treated with a proton‐pump inhibitor
Authors: Gardner J. D. , Sloan S. , Robinson M. , Miner P. B.
Published: July 2003

Background : In gastro‐oesophageal reflux disease (GERD) subjects treated with a gastric anti‐secretory agent, it is not known whether there is a relationship between heartburn severity and oesophageal acid exposure.

Methods : Oesophageal pH and heartburn severity were determined in 27 GERD subjects at baseline and on days 1, 2 and 8 of treatment with 20 mg omeprazole or 20 mg rabeprazole in a randomized, two‐way crossover fashion.

Results : Receiver operating characteristic (ROC) analysis was used to determine values for heartburn severity that gave optimal cut‐off points for distinguishing between normal and pathologic oesophageal reflux. Using these cut‐off points, we found that the probability of no pathologic oesophageal reflux (Y) could be best fitted by an exponential equation: Y = a(e–bX) + c, where a, b and c are constants and X is the value of heartburn severity. There was close agreement between predicted and observed percentages of subjects with pathologic oesophageal reflux during different days of treatment.

Conclusions : In GERD subjects treated with a proton‐pump inhibitor, the value of heartburn severity following a single standard meal can predict the likelihood of pathologic oesophageal reflux over the entire 24‐h period.
Helicobacter pylori eradication and peptic ulcer healing: the impact of deleting the proton pump inhibitor and using a once‐daily treatment
Authors: Wheeldon T‐U. , Hoang T. T. H. , Phung D. C. , Björkman A. , Granström M. , Sörberg M.
Published: July 2003

Aim: To compare cheaper and simpler once‐daily regimens, with and without a proton pump inhibitor, with standard, twice‐daily, triple therapy.

Methods: A randomized, placebo‐controlled, treatment trial in Vietnam allocated 296 Helicobacter pylori‐infected patients with peptic ulcer of ≥ 5 mm to one of three regimens: (i) twice‐daily: lansoprazole 30 mg, clarithromycin 250 mg and tinidazole 500 mg; (ii) once‐daily: lansoprazole 60 mg, clarithromycin 500 mg and tinidazole 1000 mg; (iii) once‐daily: placebo, clarithromycin 500 mg and tinidazole 1000 mg. H. pylori status was assessed by culture and immunoblot, ulcer healing by endoscopy and side‐effects by structured questionnaires.

Results: Per protocol eradication (N = 256) was higher with standard therapy (87%) than with once‐daily therapy (72%), and both were better than once‐daily therapy without proton pump inhibitor (39%). Per protocol ulcer healing after standard therapy (83%) was not significantly better than that after once‐daily therapy (73%), but better than that after therapy without proton pump inhibitor (65%). Side‐effects were reported at similar rates in all groups.

Conclusions: Proton pump inhibitor was needed for optimal eradication and ulcer healing. Twice‐daily administration showed improved success rates when compared with once‐daily therapies. Peptic ulcer healing was achieved even in patients treated with antibiotics only, confirming the central role of H. pylori in the pathophysiology of peptic ulcer disease.
A comparison of the upper gastrointestinal mucosal effects of valdecoxib, naproxen and placebo in healthy elderly subjects
Authors: Goldstein J. L. , Kivitz A. J. , Verburg K. M. , Recker D. P. , Palmer R. C. , Kent J. D.
Published: July 2003

Background : In long‐term outcomes studies, cyclooxygenase COX‐2 specific inhibitors spare COX‐1 at supratherapeutic doses and therefore demonstrate improved gastrointestinal safety over nonspecific nonsteroidal anti‐inflammatory drugs (NSAIDs). However, in clinical practice, anti‐inflammatory drugs are often used for short‐term treatment of pain.

Aim : To compare the short‐term upper gastrointestinal mucosal effects of naproxen with the new COX‐2 specific inhibitor, valdecoxib, or placebo, in elderly subjects.

Methods : In this multicentre, double‐blind, randomized, study, elderly subjects (65–76 years old), with a normal baseline esophagogastroduodenoscopy (EGD), received oral valdecoxib (a supratherapeutic 40 mg b.d. dosage, n = 62), naproxen (500 mg b.d., n = 62), or placebo (n = 62) for 6.5 days. Upper gastrointestinal mucosal injury was evaluated post‐treatment by EGD (day 7).

Results : Subjects receiving naproxen (11/60, 18%) had significantly more gastroduodenal ulcers post‐treatment than those receiving placebo (2/61, 3%; P < 0.01) or valdecoxib (0/60, 0%; P < 0.001). A similar significant finding was observed for gastric ulcer rates. All treatments had similar adverse event rates and clinical laboratory findings.

Conclusions : Valdecoxib, even at supratherapeutic doses, was associated with an ulcer rate significantly lower than naproxen but similar to placebo in healthy elderly subjects, despite the short duration of therapy (6.5 days). Naproxen and valdecoxib were as well tolerated as placebo.
Is it possible to predict treatment response to a proton pump inhibitor in functional dyspepsia?
Authors: Bolling‐Sternevald E. , Lauritsen K. , Talley N. J. , Junghard O. , Glise H.
Published: July 2003

Background: The efficacy of proton pump inhibitors in functional dyspepsia is modest and the prognostic factors are almost unknown.

Methods: Data were pooled on patients (n = 826) with a diagnosis of functional dyspepsia from two placebo‐controlled trials who were treated with omeprazole, 10 or 20 mg once daily, for 4 weeks. Self‐administered questionnaires for the assessment of symptoms and health‐related quality of life were completed before entry, and epigastric pain/discomfort was recorded on diary cards. Treatment success was defined as the complete absence of epigastric pain/discomfort on each of the last 3 days of week 4. Prognostic factors were identified by multiple logistic regression analysis.

Results: The most discriminating predictor of treatment success (P < 0.0001) was the number of days with epigastric pain/discomfort during the first week of treatment. Fewer days with symptoms during the first week led to higher response rates at 4 weeks. In addition, age > 40 years, bothersome heartburn, low scores for bloating, epigastric pain and diarrhoea, history of symptoms for < 3 months and low impairment of vitality at baseline were identified as positive predictors of outcome.

Conclusions: Early response to treatment with a proton pump inhibitor, during the first week, seems to predict the outcome after 4 weeks in patients with functional dyspepsia.
Proton‐pump inhibitor therapy for acetylsalicylic acid associated upper gastrointestinal symptoms: a randomized placebo‐controlled trial
Authors: Laheij R. J. F. , . Van Rossum L. G. M , Jansen J. B. M. J. , Verheugt F. W. A.
Published: July 2003

Objective : Patients using acetylsalicylic acid (aspirin) have an increased risk of upper gastrointestinal discomfort. The aim of this study was to assess whether gastric acid suppression improves upper gastrointestinal symptoms in patients using low‐dose aspirin for cardiovascular disease.

Methods : In a double‐blind, placebo‐controlled randomised trial, 150 patients using low‐dose (80 mg) acetylsalicylic acid with upper gastrointestinal symptoms who had been admitted at the Coronary Care Unit of the University Medical Center Nijmegen were assigned to treatment with rabeprazole (20 mg once daily) or placebo for 4 weeks. Treatment success, defined as complete upper gastrointestinal symptom relief, could be evaluated in 143 patients.

Results : At 4 weeks after randomization, 34 of the 73 patients assigned to rabeprazole therapy (47%) as compared with 30 of the 70 patients given placebo (43%) reported complete upper gastrointestinal symptom relief (P = 0.54). Rabeprazole therapy did lead to a 52% improvement of heartburn symptoms [25% vs. 16%; odds ratio (OR) 0.48, 95% confidence interval (CI): 0.24–0.97]. Epigastric pain, regurgitation, bloating and nausea symptoms did not statistically change after treatment. Patients with a history of dyspepsia more often reported treatment success in comparison to those without (75% vs. 40%; OR 0.25, 95% CI: 0.09–0.70).

Conclusions : Proton‐pump inhibitor therapy significantly reduced heartburn, but not other acetylsalicylic acid associated symptoms.
High‐dose rabeprazole–amoxicillin versus rabeprazole–amoxicillin–metronidazole as second‐line treatment after failure of the Japanese standard regimen for Helicobacter pylori infection
Authors: Isomoto H. , Inoue K. , Furusu H. , Enjoji A. , Fujimoto C. , Yamakawa M. , Hirakata Y. , Omagari K. , Mizuta Y. , Murase K. , Shimada S. , Murata I. , Kohno S.
Published: July 2003

Background : There is currently no optimal second‐line treatment after failure of Helicobacter pylori triple therapy.

Aim : To determine effective salvage therapy after failure of lansoprazole–amoxicillin–clarithromycin.

Methods : After failure of lansoprazole–amoxicillin–clarithromycin 123 out‐patients were randomized to receive either 2‐week rabeprazole (20 mg b.d.) + amoxicillin (1000 mg b.d.) (RA group) or 1‐week rabeprazole (10 mg b.d.) + amoxicillin (750 mg twice b.d.) + metronidazole (250 mg b.d.) (RAM group). Eradication was assessed by the 13C‐urea breath test. We also evaluated cytochrome p450 (CYP) 2C19 genotype status, determined by polymerase chain reaction – restriction fragment length polymorphism, and susceptibility to clarithromycin and metronidazole.

Results : On an intention‐to‐treat basis, H. pylori infection cure was achieved in 37 of 63 (59%) patients in the RA group and in 49 of 60 (82%) patients in the RAM group. Per protocol‐based eradication rates in the RA and RAM groups were 66% (37/56) and 88% (49/56), respectively. In both analytic sets there were significant differences between the treatment groups (P < 0.01 in each). Mild adverse events were observed in eight and five patients from the RA and RAM groups, respectively. Genetic predisposition of CYP2C19 and antibiotic resistance did not influence the treatment outcome either regimen.

Conclusions : The rabeprazole + amoxicillin + metronidazole therapy yielded satisfactory results. In contrast, the cure rate in high‐dose rabeprazole + amoxicillin was below an acceptable level.
The contributions of deficient androgen action in spermatogenic disorders
Authors: Ochsenkühn Robert , De Kretser David M.
Published: July 2003

The contributions of deficient androgen actions in spermatogenic disorders causing idiopathic male infertility are reviewed. The physiological role of androgens in spermatogenesis, the mechanism of actions of testosterone and the clinical implication of androgen deficiency are explained. The role of mutations in the androgen receptor (AR) in idiopathic infertility and, in particular, the contribution of expanded cytosine‐adenine‐guanine (CAG) repeats in exon 1 of the AR gene to the occurrence of male idiopathic infertility is highlighted. Possible future aspects of treatment for such patients are discussed.
Assessment of Sertoli cell functional reserve and its relationship to sperm parameters
Authors: Adamopoulos Dimitrios , Kapolla Niki , Nicopoulou Stamatina , Pappa Athina , Koukkou Eftyhia , Gregoriou Achilleas
Published: July 2003

Sertoli cell functional reserve was assessed in normozoospermic men and oligozoospermic patients and its prognostic potential was evaluated for patient selection and treatment. For the first objective, three groups of normo‐follicle‐stimulating hormone (FSH)/normozoospermic fertile men (n:12), normo‐FSH/oligozoospermic (n:21) and hyper‐FSH/oligozoospermic subfertile men participated in the study whereas for the second objective 24 normo‐FSH oligozoospermic patients volunteered for a pilot therapeutic trial. For the first part, high purity (hp) FSH (225 i.u., i.m.), human chorionic gonadotropin (hCG) (1500 i.u., i.m.) or their combination was given separately at weekly intervals, with samplings at 0, 3, 24 and 48 h. For the pilot trial, rec‐FSH (150 i.u./48 h, i.m.) or placebo were prescribed for 6 months. The main outcome measures for the study were inhibin‐B (inh‐B), insulin‐like growth factor (IGF)‐I, testosterone and oestradiol concentrations and the main sperm parameters. Bolus administration of hp‐FSH or hp‐FSH/hCG combination in normozoospermic men resulted in a significant rise of inh‐B in normozoospermic men (mean ± SD, basal: 183.8 ± 24.2 pg/mL in hp‐FSH and 175.2 ± 23.5 in hp‐FSH/hCG treatment; 48 h: 256.1 ± 34.2 and 246.3 ± 19.0, respectively, p < 0.001 for both). In oligozoospermic groups basal inh‐B concentration was lower than in normozoospermic men (normo‐FSH: 117.4 ± 16.5, hyper‐FSH: 81.2 ± 19.8, p < 0.001 for both) with a post‐stimulation increase noted only in normo‐FSH patients (hp‐FSH 24‐h: 132.8 ± 19.7, p < 0.01; hp‐FSH/hCG 0 min: 105.7 ± 20.1, 24‐h: 119.5 ± 20.6, p < 0.05). Total sperm number and progressive motility showed significant improvements (p < 0.05 for both) after 6 months of rec‐FSH treatment in the group of patients with a satisfactory response to hp‐FSH stimulation. In conclusion, the basal and reserve activity of Sertoli cells, as judged by inh‐B secretion, was higher in normozoospermic than in dyspermic men, with a better therapeutic outcome noted in those patients with an adequate response to hp‐FSH stimulation.
Clinical significance of the Acridine Orange test performed as a routine examination: comparison with the CASA estimates and strict criteria
Authors: Shibahara Hiroaki , Onagawa Tamaho , Ayustawati  , Jorsaraei Sayedgholamali , Hirano Yuki , Suzuki Tatsuya , Takamizawa Satoru , Suzuki Mitsuaki
Published: July 2003

The aim of the present study is to clarify the clinical significance of the Acridine Orange (AO) test (a sperm function test) as a routine examination by investigating the relationships between chromatin decondensation assessed by the AO test and routine semen analysis. Totally 543 semen samples were obtained from 286 infertile men. The AO test was performed, and spermatozoa displaying green fluorescence were considered as mature. The threshold of green AO fluorescence as 50% was adopted and the values <50% were considered as positive in the test. Computer‐aided sperm analysis (CASA) and strict criteria were used for routine semen analysis. Twenty‐two (4.05%) of 543 semen samples were positive in the AO test. In 20 semen samples obtained from men with severe male infertility treated by intracytoplasmic sperm injections (ICSI), the positive rate was 30.0%, which was significantly higher than that (2.63%) treated by conventional in vitro fertilization (IVF) (p = 0.01). As for the basic sperm parameters, there were significant correlations between the AO test and sperm motility (p < 0.001), and between the AO test and normal sperm morphology (p = 0.02). However, there was no relationship between the AO test and sperm concentration (p = 0.585). Sperm motion parameters assessed by CASA, including amplitude of lateral head displacement (ALH), curvilinear velocity (VCL) and rapid sperm movement (Rapid), were significantly correlated with the AO test. The information obtained using the AO test was indicated to be useful in planning treatment strategy for infertile couples.
The Spleen ofZaedyus pichiy, (Mammalia, Dasypodidae): a Light and Electron Microscopic Study
Authors: Galíndez E. J. , Estecondo S. , Casanave E. B.
Published: July 2003

Armadillos are ancient mammals important as models for biomedical, evolutive and ecological studies, because they have adaptive and primitive morpho‐physiological characteristics. In this work we study the splenic microarchitecture of the ‘Patagonian Piche’,Zaedyus pichiy, as an attempt to understand the relationship between the organizational plan of the organ and the particular features of this species.

The organ samples were classically processed for light and electron microscopic study.

The microanatomy of the organ as well as its different cell types are studied. The spleen is non‐sinusoidal, with the typical arrangement for storage functions. White pulp is well defined. Red pulp is a meshwork of circulating, immunocompetent and haemopoietic cells. The general structure of the organ agrees with the semi‐fossorial habit and the adaptability of the species. Comparative aspects with other armadillos or other less specialized groups are discussed. Persistence of haemopoietic spleen activity in the adult suggests the existence of specific inductive functions of the stroma. Better knowledge of spleen structure and function in ancient mammals may give important information about their phylogeny.
Morphometry and Histochemistry of the Semitendinosus Muscle of Tufted Capuchin Monkeys (Cebus apella Linnaeus, 1758)**
Authors: Roque D. D. , Andreo J. C. , De Oliveira J. A. , Roque J. S. , Buchaim R. L. , Rodrigues A. C.
Published: July 2003

Considering monkeys are animals closely related to the human, and semitendinosus muscle has been used in many postural research experiments, we have decided to study its histochemical characteristics. Samples were removed from the proximal, middle and distal regions of the semitendinosus muscles of five adult male tufted capuchin monkeys and observed for reaction with m‐ATPase (with alkaline and acid pre‐incubation), nicotinamide adenine dinucleotide tetrazolium reductase, and haematoxylin and eosin. The muscle fibres were classified as fast glycolytic (FG), fast oxidative glycolytic (FOG) and slow oxidative (SO) and quantified in terms of frequency and area. The three regions of the semitendinosus muscle showed no significant differences in frequency or area of the respective fibre types, and therefore the muscle can be considered histoenzymologically homogeneous. FG fibres presented higher frequencies and larger areas. The sum of FOG and SO fibres was 57.5%, suggesting that the semitendinosus muscle of the tufted capuchin monkey is adapted to an action involved in posture maintenance and in long arboreal dislocation. The present data agrees with the notion of differentiated quadrupedalism in some primates, which support a lower percentage of their weight on the fore limbs.
The Course of the Nasolacrimal Duct in Brachycephalic Cats
Authors: Breit S. , Künzel W. , Oppel M.
Published: July 2003

Casts of the nasolacrimal duct system were obtained from 50 euthanised cats including brachy‐, meso‐ and dolichocephalic breeds. The course of the nasolacrimal duct, which was assessed radiographically and gross‐anatomically, was strongly related to the shape of the skull. In meso‐ and dolichocephalic cats the nasolacrimal duct formed a dorsally opened arch with the descending part being directed rostroventrally. The main part of the duct passed the nasal cavity in a rather horizontal course parallel to the hard palate and was located ventrally to the lacrimal foramen. However, foreshortening of the face was associated with a right‐angled or even acute‐angled alignment of the duct. In higher degrees of brachycephaly the main part of the duct ascended beyond the level of the lacrimal foramen and passed the nasal cavity dorsal to the level of the lacrimal foramen. This specific course of the nasolacrimal duct in brachycephalic cats was consistent with a steeper alignment and attachment of the maxilloturbinate. Accessory orifices of the nasolacrimal duct opening into the nasal cavity had never been observed. The present results strongly suggest that the specific course of the nasolacrimal duct in brachycephalic cats might hinder the drainage of the lacrimal fluid irrespective of the diameter of the lumen of the nasolacrimal duct system.
Neurotrophin 3 and its Receptor TrkC Immunoreactivity in Glucagon Cells of Buffalo Pancreas
Authors: Lucini C. , Costagliola C. , Borzacchiello G. , Castaldo L.
Published: July 2003

Neurotrophin 3 (NT3), a member of the neurotrophin family, and its specific receptor tyrosine kinase C (TrkC) are involved in the differentiation, survival, and maintenance of many neuronal populations. Recently, NT3 and TrkC were also retained involved in the biology of non‐neuronal tissues. In this study, we report the presence of NT3‐ and TrkC‐immunoreactive cells in the endocrine pancreas of adult buffalos. They were usually distributed at the periphery of islets and showed intense immunoreactivity. By double immunohistochemical staining, NT3‐ and TrkC‐IR resulted to be colocalized in glucagon immunoreactive cells. These findings suggest endocrine and/or autocrine roles of NT3 in pancreatic A cells.
Extrinsic Cardiac Nerve Segments in the Domestic Dog (Canis familiaris– Linnaeus, 1758). Comparative Study in Young and Adult Dogs
Authors: Brugnaro M. , De Souza R. R. , Ribeiro A. A. C. M.
Published: July 2003

In this paper, important connections between the two main contingents of the autonomic nervous system, intrinsic and extrinsic visceral plexus were analysed. Concerning heart innervation, the territories of extrinsic innervation are very important in the treatment of congenital or acquired cardiopathy, thoracic neoplasia and aortic arch persistence, among others. This research compared young and adult extrinsic cardiac innervation and described the surgical anatomic nerve segments. Animals were perfused with a 10% formaldehyde solution in PBS (0.1 m) (pH 7.4) and submitted to macro‐ and meso‐scopic dissection immersed in 60% acetic acid alcoholic solution and 20% hydrogen peroxide aqueous solution. The nerve segments were assigned as: right vagus nerve segment, left vagus nerve segment, right middle cervical ganglion segment, left middle cervical ganglion segment, right caudal laryngeal nerve segment, left caudal laryngeal nerve segment, right phrenic nerve segment and left phrenic nerve segment.
Histochemical Study of Innervation and NADPH‐D Activity of the Thymus
Authors: Danko J. , Ondrašovič M. , Švický E. , Jenča A. , Pospieszny N. , Ondrašovičová O.
Published: July 2003

Acetylcholinesterase (ACHE)‐positive nerve fibres in the thymus of the rat form perivascular plexuses as well as free ACHE‐positive nerves, which do not follow the course of the vessels. A higher number of ACHE‐positive nerves was observed in corticomedullary border and the medulla, a lower number in the cortex of the thymus lobuli. A gradual reduction of ACHE‐positive intrathymus nerve formation was recorded and correlated with the increasing age of the rats. Nicotinamide adenine dinucleotide phosphate‐diaphorase positive cells observed in the rat thymus were irregular with numerous projections and were located on the boundary of the cortex and medulla.
Macro and Microstructural Organization of the Dog's Caudal Mesenteric Ganglion Complex (Canis Familiaris‐Linnaeus, 1758)
Authors: Gagliardo K. M. , Guidi W. L. , Da Silva R. A. , Ribeiro A. A. C. M.
Published: July 2003

The caudal mesenteric ganglion (CMG) is located ventral to the abdominal aorta involving the initial portion of the caudal mesenteric artery. Its macro and microstructural organization was studied in 40 domestic dogs. From the CMG, there were three nerves: the main hypogastric, the left hypogastric and the right hypogastric. The main hypogastric nerve emits two branches: the left colonic nerve and the cranial rectal nerve. Afterwards they give rise to branches to the descending colon (colonic nerves) and rectum (rectal nerves). The cranial rectal nerve, and left and right hypogastric nerves were directed to the pelvic ganglia. The microscopic study permitted the observation of the histological organization of the CMG, which is a ganglionic complex composed of an agglomeration of ganglionic units. Each ganglionic unit is composed of three major cell types: principal ganglion neurones (PGNs), glial cells and small intensely fluorescent (SIF) cells, and they were separated by nerve fibres, septa of connective tissue (types 1 and 3 collagen fibres), fibroblasts and intraganglionic capillaries. Hence, the ganglionic unit is the morphological support for the microstructural organization of the CMG complex. Further, each ganglionic unit is constituted by a cellular triad (SIF cells, PGN and glial cells), which is the cytological basis for each ganglionic unit.
Myosin Heavy Chain Isoforms of the Murine Masseter Muscle During Pre‐ and Post‐natal Development
Authors: Usami A. , Abe S. , Ide Y.
Published: July 2003

Masticatory muscles that are derived from the branchial arches express different compositions of myosin heavy chain (MHC) isoforms during the transitional phase from suckling to mastication. To clarify the developmental changes of murine masseter muscle, the composition of MHC isoforms was examined using immunohistochemical staining and competitive reverse transcription PCR. We found that MHC1 was expressed transiently in the pre and post‐natal stages. In the compositional change of isoforms, the embryonic type MHCp was expressed consistently, whereas the adult isoforms increased with the developmental process. In particular, a significant change was observed between embryonic days 14 and 16, a stage when murine facial development is conspicuous. This suggests that the development of murine masseter muscle is closely associated with facial development.
A Detailed Subgross Morphometric Study on the Auditory Ossicles of the New Zealand Rabbit
Authors: Kurtul I. , Cevik A. , Bozkurt E. U. , Dursun N.
Published: July 2003

This study was designed to reveal, in detail, the features of the auditory ossicles of the New Zealand rabbit, one of the most frequently used animals in scientific researches. Heads of 10 dead adult New Zealand rabbits of both sexes weighing 2.5 ± 0.2 kg were used in the study. The auditory ossicles were gently removed from their situs and observed. The auditory ossicles were three small bones: the malleus, the incus and the stapes. The lenticular bone seemed to be the lenticular process, as is in human beings. In general, macroanatomic features of the bones were similar to those reported in the literature. Findings in this study, however, differed greatly, especially in detail. There were statistically significant differences in the morphometric data of the features of the auditory ossicles between the right‐ and left‐hand sides. Data from the right‐hand side were significantly higher.
Histochemical alterations of re‐innervated rat extensor digitorum longus muscle after end‐to‐end or graft repair: a comparative histomorphological study
Authors: Lehnert M. , Steudel W. I. , Marzi I. , Mautes A.
Published: July 2003

Changes in the histochemical profile of 43 rat extensor digitorum longus muscles undergoing de‐innervation and re‐innervation were recorded. Assessment of fibre type composition and muscle fibre cross‐sectional area was performed at 15, 30, 90 and 180 days post operative (p.o.) after either primary end‐to‐end repair or autologous graft repair of the common peroneal nerve (n= 5 per time point and type of repair). The size and histochemical profile of single muscle fibres were analysed by computer‐assisted quantification on the basis of their myofibrillar ATPase (pH 4.3) and succinate dehydrogenase (SDH) activities in serial, whole‐muscle cross‐sections. Accordingly, four muscle‐fibre types could be functionally identified: (1) slow oxidative (SO, type I); (2) fast‐oxidative glycolytic (FOG, type IIA); (3) fast glycolytic (FG, type IIB); and (4) succinate dehydrogenase intermediate (SDH‐INT). At 15 days following end‐to‐end repair, the SDH‐INT muscle fibre type was observed. By contrast, 15 days following graft repair, no changes in fibre type composition were observed (vs. control). At 30 days p.o. in the group that received end‐to‐end repair, type SDH‐INT reached its maximum and was significantly higher than in the group that underwent graft repair. At 90 days p.o., the amount of SDH‐INT fibres declined after end‐to‐end repair, but it was still significantly higher than in the group treated with a nerve graft. The increase of the SDH‐INT fibre type was mirrored by a proportional disappearance of FG and FOG fibres. These changes were time‐dependent, not reversible at 180 days p.o and largely blunted after nerve graft. Muscle‐fibre size decreased at 15 and 30 days after both types of nerve repair. This decrease was transient and reversible within 90 days p.o. These findings reflect the fact that the reorganization of the histochemical profile in re‐innervated muscles is both time dependent and long lasting. The degree of this reorganization is significantly higher after end‐to‐end repair than after graft repair.
Muscle satellite (stem) cell activation during local tissue injury and repair
Authors: Hill Maria , Wernig A. , Goldspink G.
Published: July 2003

In post‐mitotic tissues, damaged cells are not replaced by new cells and hence effective local tissue repair mechanisms are required. In skeletal muscle, which is a syncytium, additional nuclei are obtained from muscle satellite (stem) cells that multiply and then fuse with the damaged fibres. Although insulin‐like growth factor‐I (IGF‐I) had been previously implicated, it is now clear that muscle expresses at least two splice variants of the IGF‐I gene: a mechanosensitive, autocrine, growth factor (MGF) and one that is similar to the liver type (IGF‐IEa). To investigate this activation mechanism, local damage was induced by stretch combined with electrical stimulation or injection of bupivacaine in the rat anterior tibialis muscle and the time course of regeneration followed morphologically. Satellite cell activation was studied by the distribution and levels of expression of M‐cadherin (M‐cad) and related to the expression of the two forms of IGF‐I. It was found that the following local damage MGF expression preceded that of M‐cad whereas IGF‐IEa peaked later than M‐cad. The evidence suggests therefore that an initial pulse of MGF expression following damage is what activates the satellite cells and that this is followed by the later expression of IGF‐IEa to maintain protein synthesis to complete the repair.
Measurement of the linear dynamics of the descent of the bovine fetal testis
Authors: Edwards M. J. , Smith M. S. R. , Freeman B.
Published: July 2003

Measurements were made on 86 male bovine fetuses collected from abattoirs in the vicinity of Sydney, Australia. The fetal body length was used to calculate the approximate day of gestational age (DGA); most fetuses were between 60 and 150 DGA. The distances from the caudal pole of the kidney (metanephros) to, respectively, the tip of the scrotum, the distal end of the testis and the internal ring of the inguinal canal were measured, as well as the dimensions of the testis and gubernaculum testis. Distances of (1) testis to inguinal canal, (2) inguinal canal to scrotum, (3) testis to scrotum and (4) gubernaculum to scrotum were calculated from these measurements, which were made on both left and right sides. The total length of the gubernaculum testis increased during transabdominal passage and during transinguinal passage of the testis. Furthermore, the gubernaculum appeared to maintain the testis at a relatively fixed distance from the scrotum during transabdominal passage so that the inguinal canal appeared to move towards the testis. The greatest distance between the testis and the tip of the scrotum was found during the transinguinal passage of the testis and was 2.8 cm for the left testis and 2.3 cm for the right. When located within the scrotum, each testis was still 1.6–1.7 cm from the tip of the scrotum, so the distance to be traversed was only 0.6–1.2 cm. Following passage of the testis through the inguinal canal, the gubernaculum became shorter and its distal tip was displaced toward the distal end of the scrotum. Traction by the gubernaculum could account for the final transposition of the testis from the external inguinal ring to the scrotum. Other factors involved in displacement of the testis include differential growth patterns as well as increases in the dimensions of the testis itself.
Neurotrophins and the immune system
Authors: Vega José A. , García‐Suárez Olivia , Hannestad Jonas , Pérez‐Pérez Marta , Germanà Antonino
Published: July 2003

The neurotrophins are a family of polypeptide growth factors that are essential for the development and maintenance of the vertebrate nervous system. In recent years, data have emerged indicating that neurotrophins could have a broader role than their name might suggest. In particular, the putative role of NGF and its receptor TrkA in immune system homeostasis has become a much studied topic, whereas information on the other neurotrophins is scarce in this regard. This paper reviews what is known about the expression and possible functions of neurotrophins and their receptors in different immune tissues and cells, as well as recent data obtained from studies of transgenic mice in our laboratory. Results from studies to date support the idea that neurotrophins may regulate some immune functions. They also play an important role in the development of the thymus and in the survival of thymocytes.
Force‐ and moment‐generating capacities of muscles in the distal forelimb of the horse
Authors: Brown Nicholas A. T. , Pandy Marcus G. , Kawcak Christopher E. , McIlwraith C. Wayne
Published: July 2003

A detailed musculoskeletal model of the distal equine forelimb was developed to study the influence of musculoskeletal geometry (i.e. muscle paths) and muscle physiology (i.e. force–length properties) on the force‐ and moment‐generating capacities of muscles crossing the carpal and metacarpophalangeal joints. The distal forelimb skeleton was represented as a five degree‐of‐freedom kinematic linkage comprised of eight bones (humerus, radius and ulna combined, proximal carpus, distal carpus, metacarpus, proximal phalanx, intermediate phalanx and distal phalanx) and seven joints (elbow, radiocarpal, intercarpal, carpometacarpal, metacarpophalangeal (MCP), proximal interphalangeal (pastern) and distal interphalangeal (coffin)). Bone surfaces were reconstructed from computed tomography scans obtained from the left forelimb of a Thoroughbred horse. The model was actuated by nine muscle–tendon units. Each unit was represented as a three‐element Hill‐type muscle in series with an elastic tendon. Architectural parameters specifying the force‐producing properties of each muscle–tendon unit were found by dissecting seven forelimbs from five Thoroughbred horses. Maximum isometric moments were calculated for a wide range of joint angles by fully activating the extensor and flexor muscles crossing the carpus and MCP joint. Peak isometric moments generated by the flexor muscles were an order of magnitude greater than those generated by the extensor muscles at both the carpus and the MCP joint. For each flexor muscle in the model, the shape of the maximum isometric joint moment–angle curve was dominated by the variation in muscle force. By contrast, the moment–angle curves for the muscles that extend the MCP joint were determined mainly by the variation in muscle moment arms. The suspensory and check ligaments contributed more than half of the total support moment developed about the MCP joint in the model. When combined with appropriatein vivomeasurements of joint kinematics and ground‐reaction forces, the model may be used to determine muscle–tendon and joint–reaction forces generated during gait.
The detection of mature T‐ and B‐cells during development of the lymphoid tissues of the tammar wallaby (Macropus eugenii)
Authors: Old J. M. , Deane E. M.
Published: July 2003

The distribution of T‐ and B‐cells in the developing lymphoid and immunohaematopoietic tissues of the tammar wallaby were investigated using antibodies to the mature cell surface markers, CD3, CD5 and CD79b. In the thymus, CD3‐ and CD5‐positive T‐cells were first observed at day 12 postpartum whilst rare B‐cells were first detected at day 23. Both T‐ and B‐lymphocytes were first stained on day 21 postpartum in the spleen and day 24 in lymph nodes. In one sample from a 7‐day‐old animal, rare CD79b‐positive (CD79b+) lymphocytes were observed in the gut‐associated lymphoid tissues. However, CD3+ cells were not apparent until day 12 and CD5+ cells were not detected until day 74 postpartum. No lymphocytes were detected in liver or bone marrow samples and no bronchus‐associated lymphoid tissues were observed. The pattern of development and the distribution of T‐ and B‐cells in the lymphoid and immunohaematopoietic tissues were similar to those observed in eutherian mammals and in limited studies of other metatherians. However, the detection of apparently mature T‐ and B‐cells in the thymus and gut‐associated lymphoid tissues (GALT) at the same postnatal age highlights the need for a more substantial study of the development of GALT. This is, at present, limited by availability of marsupial‐specific antibodies.
Ultrastructural distribution of glycinergic and GABAergic neurons and axon terminals in the rat dorsal cochlear nucleus, with emphasis on granule cell areas
Authors: Alibardi Lorenzo
Published: July 2003

A knowledge of neurotransmitters in the neurons of the rat cochlear nuclear complex is of importance in understanding the function of auditory circuits. Using post‐embedding ultrastructural immunogold labelling, the distribution of glycinergic and GABAergic neurons and axonal terminals has been studied in the molecular, fusiform and polymorphic layers of the rat dorsal cochlear nucleus (DCN). This technique is not limited by the penetration of antibodies into the nervous tissue as in pre‐embedding methods, and allows a fine neurochemical mapping of the nervous tissue. Numerous glycinergic and GABAergic axon terminals contain pleomorphic and flat synaptic vesicles, and are present in all layers (1, 2, 3) of the dorsal cochlear nucleus. Glycine and GABA‐negative large terminals (mossy fibres) are mainly seen in granule cell areas of layer 2 (fusiform layer). Mossy fibres contact the dendrites of GABA‐ and glycine‐negative granule cells and of the few unipolar brush cells (excitatory neurons). The least common cells in the granule cell areas are GABAergic and glycinergic Golgi‐stellate neurons. In unipolar brush cells, aggregations of vesicles seem to be the origin of their characteristic ringlet‐bodies. Golgi‐stellate cells send their inhibitory terminals to the dendrites of granule and unipolar brush cells, occasionally directly to mossy fibres. Small or (less frequently) large GABAergic terminals contact the soma or the main dendrite of unipolar brush cells. The circuit of a hypothetical functional unit of neurons in the DCN is proposed. The inputs from auditory tonotopic or non‐auditory non‐tonotopic mossy fibres eventually reach pyramidal cells through axons from the granule cells or unipolar brush cells. Pyramidal cells convey an excitatory signal from the DCN to higher mesencephalic nuclei for further elaboration of the acoustic signal.
Chlamydomonas reinhardtii as a eukaryotic photosynthetic model for studies of heavy metal homeostasis and tolerance
Authors: Hanikenne M.
Published: July 2003

The green alga Chlamydomonas reinhardtii is a useful model of a photosynthetic cell. This unicellular eukaryote has been intensively used for studies of a number of physiological processes such as photosynthesis, respiration, nitrogen assimilation, flagella motility and basal body function. Its easy‐to‐manipulate and short life cycle make this organism a powerful tool for genetic analysis. Over the past 15 yr, a dramatically increased number of molecular technologies (including nuclear and organellar transformation systems, cosmid, yeast artificial chromosome (YAC) and bacterial artificial chromosome (BAC) libraries, reporter genes, RNA interference, DNA microarrays, etc.) have been applied to Chlamydomonas. Moreover, as parts of the Chlamydomonas genome project, molecular mapping, as well as whole genome and extended expressed sequence tag (EST) sequencing programs, are currently underway. These developments have allowed Chlamydomonas to become an extremely valuable model for molecular approaches to heavy metal homeostasis and tolerance in photosynthetic organisms.
Thlaspi caerulescens, an attractive model species to study heavy metal hyperaccumulation in plants
Authors: Assunção Ana G. L. , Schat Henk , Aarts Mark G. M.
Published: July 2003

Studying heavy metal hyperaccumulation is becoming more and more interesting for ecological, evolutionary, nutritional, and environmental reasons. One model species, especially in the era of high throughput genomics, transcriptomics, proteomics and metabolomics technologies, would be very advantageous. Although there are several hyperaccumulator species known, there is no single model species yet. The Zn, Cd and Ni hyperaccumulator species Thlaspi caerulescens has been studied to a great extent, especially for Zn and Cd hyperaccumulation and tolerance. Its physiological, morphological and genetic characteristics, and its close relationship to Arabidopsis thaliana, the general plant reference species, make it an excellent candidate to be the plant heavy metal hyperaccumulation model species.