Understanding of and attitudes to xenotransplantation: a survey among Italian university students

Xenotransplantation is currently at the experimental stages on animal models and many problems still have to be overcome in the biomedical, immunological and ethical fields. Moreover, people's attitudes to xenotransplantation vary: surveys among intensive-care staff have revealed negative opinions, while the general public and students seem to be more positive. Little is known about the influence of schooling and the choice of university faculty on attitudes to xenotransplantation. The aims of this study were: (i) to evaluate university students' attitudes to xenotransplantation; (ii) to investigate any socio-demographic, religious and educational determinants behind students' opinions on xenotransplantation. University undergraduates on five different courses were surveyed at Padua University. A 24-item questionnaire was distributed to students at the end of lectures and completed anonymously immediately after its distribution. No information was given to students beforehand. Statistical analysis: chi-squared, Pearson's test; P-values <0.05 were considered significant. A total of 585 of 602 (97.2%) students completed the questionnaire (132 males, 453 females, mean age 20.4, range 19 to 43 yr). They were on courses in Medicine (33.85%), Agriculture (5.98%), Veterinary Medicine (11.45%), Psychology (18.46%) and Educational Sciences (30.26%). As for their previous schooling, they came from classical or scientific high school (58.3%), technical college (14.7%), language college (6.3%), teacher training college (11.9%) or others (8.8%). Concerning their religious beliefs, 83% were Catholics, and 56.2% defined themselves as practising Catholics. Eighty-eight percentage of the students knew of the possibility of animal organs being transplanted into humans and 77.9% of them approved of this idea. When grouped according to gender and education, a higher proportion of students approving of xenotransplantation were male (P = 0.017) and had attended classical or scientific high school (P = 0.011). Disapproval for moral, ethical or religious reasons was higher among practising than among non-practising Catholics; the latter rejected xenotransplantation more for immunological and infectious reasons (P = 0.014). As for the type of university course, a higher proportion of students approving of xenotransplantation attended science courses (Veterinary Medicine, Agriculture and Medicine vs. Educational Sciences and Psychology) (P = 0.013). University students generally approved of xenotransplantation. Male gender and a high-school education were associated with a greater acceptance of xenotransplantation. Practising vs. non-practising Catholics reported significantly different reasons for any disapproval of xenotransplantation. The choice of a science rather than an arts faculty at university was more strongly associated with a positive opinion on xenotransplantation.     

Solution structure of amyloid beta-peptide (25-35) in different media

The design of molecules able to interact with the amyloid peptides either as inhibitors of fibril formation or as inhibitors of amyloid membrane pore formation represents one of the most relevant approaches in the development of anti-Alzheimer therapies. Abeta-(25-35), sequence GSNKGAIIGLM, is a highly toxic synthetic derivative of amyloid beta-peptides (Abeta-peptides), which forms fibrillary aggregates. Here, we report the NMR and CD investigation of Abeta-(25-35) in a membrane-mimicking environment and in isotropic mixtures of water and fluoro-alcohols to scan its conformational properties as a function of the medium. The analysis of the 3D structures in the mentioned conditions indicates a propensity of the peptide to behave as a typical transmembrane helix in the lipidic environment. In media characterized by different polarity, it loses the structural regularity at specific points of the sequence as a function of the environment. Furthermore, a comparison with the solution structure of full-length amyloid peptides suggests a role for the 25-27 kink region, which appears to be a general feature of all peptides under the solution conditions explored.     

Isolated visceral small artery fibromuscular hyperplasia-induced ischemic colitis mimicking inflammatory bowel disease

A unique case of fibromuscular hyperplasia (FMH) of the visceral vasculature is presented. A 31-yr-old patient presented with a chronic colitis initially diagnosed as ulcerative colitis 1 yr earlier. On presentation, the endoscopic appearance showed deep linear ulcerations and cobblestoning and was more consistent with Crohn's disease. Biopsies of the area, however, suggested an ischemic etiology. The patient failed to respond to local 5ASA and prednisone therapy and progression of the disease led to a left hemicolectomy. A diagnosis of a small vessel fibromuscular arteriopathy was made on the resected specimen. This is the first case presentation of FMH mimicking inflammatory bowel disease. The lack of any systemic involvement of FMH with isolated small vessel disease has never been reported and serves as an index case of which clinicians should be aware. The literature is reviewed and the possible implications are discussed.     

Proteinase-activated receptor-1 (PAR-1) activation contracts the isolated human renal artery in vitro

1. The in vitro motor function of protease-activated recepter-1 (PAR-1), PAR-2 and PAR-4 and the presence by immunohistochemistry of PAR-1 in the human renal artery have been investigated. 2. Thrombin and the human PAR-1 (SFLLRN-NH(2)) activating peptide, but not the PAR-1 reverse peptide (NRLLFS-NH(2)), contracted both endothelial-intact and endothelial-denuded human renal artery strips, whereas no relaxation was observed either in strips non-precontracted or precontracted with phenylephrine. Maximum contraction by thrombin or SFLLRN-NH(2) was about 60% of phenylephrine. However, thrombin was approximately 1000-fold more potent than SFLLRN-NH(2). 3. PAR-1 desensitisation, using repeated applications of SFLLRN-NH(2), almost completely blocked the response to thrombin. The contractile effect produced by thrombin and SFLLRN-NH(2) was not affected by nitric oxide synthase inhibition, but was significantly reduced by cyclooxygenase blockade. 4. Trypsin, the PAR-2 (SLIGKV-NH(2) and SLIGRL-NH(2)) and PAR-4 (GYPGQV-NH(2) and AYPGKF-NH(2)) activating peptides did not produce any significant contraction or relaxation. 5. In agreement with the motor function data immunohistochemistry showed specific staining patterns for PAR-1 in the human renal artery. 6. Combined, these studies would suggest a possible role for PAR-1 in renal vascular homeostasis.     

Canalisation in human growth: a widely accepted concept reconsidered

According to the concept of canalisation, infants and children stay within one or two growth channels, and therefore, any crossing of height centiles always warrants further evaluation. In view of evidence against this concept we re-investigated the variability of individual growth in the First Zürich Longitudinal Growth Study. The investigation is based on height measurements of 232 children (112 females, 120 males) measured at annual intervals during childhood and half-yearly during adolescence. Height data were transformed into height standard deviation scores (SDS) and canalisation defined by the width of an individual's growth channel, i.e., by the differences between maximum and minimum height SDS, in the individual series of measurements. Many subjects of the First Zürich Longitudinal Growth Study crossed numerous centiles with patterns that often seemed to show characteristic features. For approximately two thirds of the subjects, the SDS channel during the whole growth process covers more than one SDS. In childhood, between the age of two and age of minimal height velocity, only about one fourth of the subjects have an SDS channel below 0.5, indicating acceptable canalisation. During childhood, growth in boys appeared slightly more canalised than in girls (P=0.02). Conclusion The present investigation does not support the concept of strict canalisation of individual growth. We suggest to consider crossing of centiles a normal event in child development, though in a clinical setting crossing centiles should still be taken seriously, at least at first until a medical cause for this has been excluded. Received: 25 July 2000 / Accepted: 11 October 2000     

Inhibition of human multidrug resistance P-glycoprotein 1 by analogues of a potent δ-opioid antagonist

Analogues Dmt-Tic (2′,6′-dimethyl- -tyrosine-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) pharmacophore, a potent δ-opioid receptor antagonist, inhibited hMDR1 P-GP expressed in a G-185 fibroblast cell line in a manner similar to verapamil. N,N(Me)₂-Dmt-Tic-NH-1-adamantane, H-Dmt-Tic-NH-1-adamantane, H-Dmt-Tic-Ala-NH-1-adamantane and N,N(Me)₂-Dmt-Tic-NH-tBut were highly effective inhibitors. Weaker inhibition was observed with N,N(Et)₂-Dmt-Tic-OH, H-Dmt-Tic-Ala-NH-tert-butyl amide and cyclo(Dmt-Tic). Results demonstrate that N- and C-terminal hydrophobic/lipophilic analogues of the Dmt-Tic pharmacophore inhibit hMDR1 and point to a potential role as chemosensitizing agents in chemotherapy for cancers containing hMDR1.     

Electrochemical surface reactions of intermediates formed in the oxidative ethanol adsorption on porous Pt and PtRu

The oxidative ethanol adsorption and electrochemical surface reactions of adsorbed intermediates were studied on electrodeposited Pt, Ru, Pt_0.92Ru_0.08 and Pt_0.85Ru_0.15 in 1 M HClO₄. A flow cell procedure was performed in order to separate surface reactions of intermediates formed in the oxidative ethanol adsorption from those reactions for ethanol in the bulk electrolyte solution. Oxidation and reduction reactions of adsorbed species were studied by potential-controlled electrodesorption spectrometry. No adsorbate formation was observed on a pure Ru electrode. In all cases, CO₂ was the sole product formed in the oxidative electrodesorption of the adsorbates. Using ¹²CH₃¹²CH₂OH and ¹²CH₃¹³CH₂OH, the oxidation reaction pathways of each C-atom to CO₂ were followed. On the other hand, methane and ethane were detected during the reductive electrodesorption of adlayer species. The onset potential for these reduction products shifts to more negative potentials as the Ru content of the alloy increases. The methane to ethane yield ratio decreases in the sequence Pt>Pt_0.92Ru_0.08>Pt_0.85Ru_0.15. A critical interpretation of the experimental data leads to a tentative yield of different adsorbed species as function of the Ru surface concentration.     

Immunoglobulin G levels during collection of large volume plasma for fractionation

Background

There is a need of comprehensive work dealing with the quality of plasma for fractionation with respect to the IgG content as today most plasma derivates are used to treat patients with immunodeficiencies and autoimmune disorders. Therefore, a prospective study was carried out to analyse IgG levels before plasmapheresis and every 200 ml collected plasma.

Combined liver-kidney transplantation in a 15-year-old boy with alpha1-antitrypsin deficiency

Alpha1-antitrypsin (1-AT) deficiency is the most common genetic cause of liver disease in infants and children. The major clinical manifestations include liver disease (primarily in children) and emphysema in adults. For patients who progress to cirrhosis and liver failure, liver transplantation provides a metabolic cure for the deficiency and presumably prevents the associated complications. Several case reports in the pediatric literature describe glomerulonephritis in the setting of severe 1-AT deficiency, but this association is less well documented in adults. End-stage chronic kidney disease is a rare finding in the literature and kidney transplantation is the treatment of choice. We report on a 15-year-old boy with 1-AT deficiency and consequent end-stage liver disease and membranoproliferative glomerulonephritis rapidly progressing to renal failure, who successfully underwent combined liver-kidney transplantation.