The bridging of pluralistic visions of science and ethics for bioethics - Tibetan medicine as compared with the Western research on longevity and human genetic enhancement

La thèse examine les liens entre la vision pluraliste de la science et l’éthique de la médecine tibétaine et les nouvelles pratiques en médecine occidentale, soit la longévité et la recherche sur la génétique amélioratrice. Elle cherche à cerner l’apport que la médecine tibétaine peut apporter aux recherches occidentales sur la longévité et la génétique humaine amélioratrice. Elle traite donc d’un enjeu social clé et du débat qui s’y rattache. La découverte et la description sont centrales à la méthodologie et informent l’analyse. Nous avons examiné dans un premier temps, les travaux de recherche sur la longévité reliée à la génétique amélioratrice (mémoire et muscles). Nous nous sommes penchés également sur les fondements de la médecine tibétaine en tant que système intégré. Pour ce faire, nous avons traité des notions telles que la santé, l’identité, la perfection et l’immortalité. Notre cadre conceptuel repose sur la théorie bouddhiste de l’interdépendance qui se caractérise par la formulation de catégories qui ensuite sont synthétisées dans l’essence; les deux niveaux d’interprétation de la théorie sont décrits en détail avant de passer à une comparaison avec la notion de complexité occidentale. La médecine tibétaine de fait présente un système où l’éthique et la science sont intégrées et se prête bien à une comparaison avec la vision pluraliste de la science à partir d’une perspective éthique/bioéthique. Les commentaires recueillis auprès des experts nous ont permis de cerner comment la science, l’éthique et l’amélioration de la longévité sont définies au sein des deux paradigmes de l’Est et de l’Ouest. Nos résultats montrent six points qui se dégagent au terme de cette recherche permettent de jeter un pont sur la vision pluraliste de ces paradigmes. Ceux-ci transcendent les points de vue doctrinaux individuels de religions ainsi que du monde scientifique occidental. Plus que tout, ils laissent entrevoir un cadre de références novatrices qui contribuera à la prise de décision à l’égard de questionnements bioéthiques.

Transplants: bioethics and justice

Bioethics, as a branch of philosophy that focuses on questions relative to health and human life, is closely tied to the idea of justice and equality. As such, in understanding the concept of equality in its original sense, that is, in associating it to the idea to treat "unequals" (those who are unequal or different, in terms of conditions or circumstances) unequally (differentially), in proportion to their inequalities (differences), we see that the so-called "one-and-only waiting list" for transplants established in law no. 9.434/97, ends up not addressing the concept of equality and justice, bearing upon bioethics, even when considering the objective criteria of precedence established in regulation no. 9.4347/98, Thus, the organizing of transplants on a one-and-only waiting list, with a few exceptions that are weakly applicable, without a case by case technical and grounded analysis, according to each particular necessity, ends up institutionalizing inequalities, condemning patients to happenstance and, consequently, departs from the ratio legis, which aims at seeking the greatest application of justice in regards to organ transplants. We conclude, therefore, that from an analysis of the legislation and of the principles of bioethics and justice, there is a need for the creation of a collegiate of medical experts, that, based on medical criteria and done in a well established manner, can analyze each case to be included on the waiting list, deferentially and according to the necessity; thus, precluding that people in special circumstances be treated equal to people in normal circumstances.

EVALUATION OF THE PERCEPTION TOWARDS RESEARCH INVOLVING HUMAN BEINGS IN BRASILEAN POST DEGREE STUDENTS

In Brazil, research involving human beings must obey to ethical norms foresaw by the 196/96 National Health Council Resolution of the Ministry of Health. This paper gives account of a knowledge evaluation about some concepts and rules established by the resolution by Dental post degree students. It is concluded that in spite of the spreading and importance of the resolution most students do not know about it. In the same situation are those who work in research.

Committees for ethics in research involving human subjects

In Brazil since October 1996 there have been guidelines for research involving human subjects. Now human subjects know when their treatment is part of research. Deceit is no longer tolerated. But is not enough to say we offer an explanation to the potential subject and we offer a choice before he or she is confronted with an informed consent form. As in all professional activity, scientific investigation needs social controls. In Brazil, the ultimate responsibility of an investigation lies on the investigator, but in every institution where research is carried out there is a Committee for Ethics in Research. All Committees are subordinated to the National Commission of Ethics in Research, which is submitted to the Brazilian Institute of Health. During 2005 around 17,000 protocols involving 700,000 human subjects were revised by 475 Committees distributed all over the country. Approximately 7,000 people are now working in these Committees.

Technicians of Human Dignity : Bodies, Souls, and the Making of Intrinsic Worth /

Tracks the development of the concept of human dignity in post-war ethics and politics, focusing on the Vatican, the United Nations, and U.S. Federal Bioethics. This title was made Open Access by libraries from around the world through Knowledge Unlatched.

Prognostic Value Of Dna And Mrna E6/e7 Of Human Papillomavirus In The Evolution Of Cervical Intraepithelial Neoplasia Grade 2.

This study aimed at evaluating whether human papillomavirus (HPV) groups and E6/E7 mRNA of HPV 16, 18, 31, 33, and 45 are prognostic of cervical intraepithelial neoplasia (CIN) 2 outcome in women with a cervical smear showing a low-grade squamous intraepithelial lesion (LSIL). This cohort study included women with biopsy-confirmed CIN 2 who were followed up for 12 months, with cervical smear and colposcopy performed every three months. Women with a negative or low-risk HPV status showed 100% CIN 2 regression. The CIN 2 regression rates at the 12-month follow-up were 69.4% for women with alpha-9 HPV versus 91.7% for other HPV species or HPV-negative status (P < 0.05). For women with HPV 16, the CIN 2 regression rate at the 12-month follow-up was 61.4% versus 89.5% for other HPV types or HPV-negative status (P < 0.05). The CIN 2 regression rate was 68.3% for women who tested positive for HPV E6/E7 mRNA versus 82.0% for the negative results, but this difference was not statistically significant. The expectant management for women with biopsy-confirmed CIN 2 and previous cytological tests showing LSIL exhibited a very high rate of spontaneous regression. HPV 16 is associated with a higher CIN 2 progression rate than other HPV infections. HPV E6/E7 mRNA is not a prognostic marker of the CIN 2 clinical outcome, although this analysis cannot be considered conclusive. Given the small sample size, this study could be considered a pilot for future larger studies on the role of predictive markers of CIN 2 evolution.

Integrated Proteomics Identified Up-regulated Focal Adhesion-mediated Proteins In Human Squamous Cell Carcinoma In An Orthotopic Murine Model.

Understanding the molecular mechanisms of oral carcinogenesis will yield important advances in diagnostics, prognostics, effective treatment, and outcome of oral cancer. Hence, in this study we have investigated the proteomic and peptidomic profiles by combining an orthotopic murine model of oral squamous cell carcinoma (OSCC), mass spectrometry-based proteomics and biological network analysis. Our results indicated the up-regulation of proteins involved in actin cytoskeleton organization and cell-cell junction assembly events and their expression was validated in human OSCC tissues. In addition, the functional relevance of talin-1 in OSCC adhesion, migration and invasion was demonstrated. Taken together, this study identified specific processes deregulated in oral cancer and provided novel refined OSCC-targeting molecules.

Hypertrophic Adenoid Is A Major Infection Site Of Human Bocavirus 1.

Human bocavirus 1 (HBoV1) is associated with respiratory infections worldwide, mainly in children. Similar to other parvoviruses, it is believed that HBoV1 can persist for long periods of time in humans, probably through maintaining concatemers of the virus single-stranded DNA genome in the nuclei of infected cells. Recently, HBoV-1 was detected in high rates in adenoid and palatine tonsils samples from patients with chronic adenotonsillar diseases, but nothing is known about the virus replication levels in those tissues. A 3-year prospective hospital-based study was conducted to detect and quantify HBoV1 DNA and mRNAs in samples of the adenoids (AD), palatine tonsils (PT), nasopharyngeal secretions (NPS), and peripheral blood (PB) from patients undergoing tonsillectomy for tonsillar hypertrophy or recurrent tonsillitis. HBoV1 was detected in 25.3% of the AD samples, while the rates of detection in the PT, NPS, and PB samples were 7.2%, 10.5%, and 1.7%, respectively. The viral loads were higher in AD samples, and 27.3% of the patients with HBoV had mRNA detectable in this tissue. High viral loads and detectable mRNA in the AD were associated with HBoV1 detection in the other sample sites. The adenoids are an important site of HBoV1 replication and persistence in children with tonsillar hypertrophy. The adenoids contain high HBoV1 loads and are frequently positive for HBoV mRNA, and this is associated with the detection of HBoV1 in secretions.

The Effect Of Celastrol, A Triterpene With Antitumorigenic Activity, On Conformational And Functional Aspects Of The Human 90kda Heat Shock Protein Hsp90α, A Chaperone Implicated In The Stabilization Of The Tumor Phenotype.

Hsp90 is a molecular chaperone essential for cell viability in eukaryotes that is associated with the maturation of proteins involved in important cell functions and implicated in the stabilization of the tumor phenotype of various cancers, making this chaperone a notably interesting therapeutic target. Celastrol is a plant-derived pentacyclic triterpenoid compound with potent antioxidant, anti-inflammatory and anticancer activities; however, celastrol's action mode is still elusive. In this work, we investigated the effect of celastrol on the conformational and functional aspects of Hsp90α. Interestingly, celastrol appeared to target Hsp90α directly as the compound induced the oligomerization of the chaperone via the C-terminal domain as demonstrated by experiments using a deletion mutant. The nature of the oligomers was investigated by biophysical tools demonstrating that a two-fold excess of celastrol induced the formation of a decameric Hsp90α bound throughout the C-terminal domain. When bound, celastrol destabilized the C-terminal domain. Surprisingly, standard chaperone functional investigations demonstrated that neither the in vitro chaperone activity of protecting against aggregation nor the ability to bind a TPR co-chaperone, which binds to the C-terminus of Hsp90α, were affected by celastrol. Celastrol interferes with specific biological functions of Hsp90α. Our results suggest a model in which celastrol binds directly to the C-terminal domain of Hsp90α causing oligomerization. However, the ability to protect against protein aggregation (supported by our results) and to bind to TPR co-chaperones are not affected by celastrol. Therefore celastrol may act primarily by inducing specific oligomerization that affects some, but not all, of the functions of Hsp90α. To the best of our knowledge, this study is the first work to use multiple probes to investigate the effect that celastrol has on the stability and oligomerization of Hsp90α and on the binding of this chaperone to Tom70. This work provides a novel mechanism by which celastrol binds Hsp90α.

Lawsonia Inermis-mediated Synthesis Of Silver Nanoparticles: Activity Against Human Pathogenic Fungi And Bacteria With Special Reference To Formulation Of An Antimicrobial Nanogel.

Lawsonia inermis mediated synthesis of silver nanoparticles (Ag-NPs) and its efficacy against Candida albicans, Microsporum canis, Propioniabacterium acne and Trichophyton mentagrophytes is reported. A two-step mechanism has been proposed for bioreduction and formation of an intermediate complex leading to the synthesis of capped nanoparticles was developed. In addition, antimicrobial gel for M. canis and T. mentagrophytes was also formulated. Ag-NPs were synthesized by challenging the leaft extract of L. inermis with 1 mM AgNO₃. The Ag-NPs were characterized by Ultraviolet-Visible (UV-Vis) spectrophotometer and Fourier transform infrared spectroscopy (FTIR). Transmission electron microscopy (TEM), nanoparticle tracking and analysis sytem (NTA) and zeta potential was measured to detect the size of Ag-NPs. The antimicrobial activity of Ag-NPs was evaluated by disc diffusion method against the test organisms. Thus these Ag-NPs may prove as a better candidate drug due to their biogenic nature. Moreover, Ag-NPs may be an answer to the drug-resistant microorganisms.

Overlapped Sequence Types (sts) And Serogroups Of Avian Pathogenic (apec) And Human Extra-intestinal Pathogenic (expec) Escherichia Coli Isolated In Brazil.

Avian pathogenic Escherichia coli (APEC) strains belong to a category that is associated with colibacillosis, a serious illness in the poultry industry worldwide. Additionally, some APEC groups have recently been described as potential zoonotic agents. In this work, we compared APEC strains with extraintestinal pathogenic E. coli (ExPEC) strains isolated from clinical cases of humans with extra-intestinal diseases such as urinary tract infections (UTI) and bacteremia. PCR results showed that genes usually found in the ColV plasmid (tsh, iucA, iss, and hlyF) were associated with APEC strains while fyuA, irp-2, fepC sitDchrom, fimH, crl, csgA, afa, iha, sat, hlyA, hra, cnf1, kpsMTII, clpVSakai and malX were associated with human ExPEC. Both categories shared nine serogroups (O2, O6, O7, O8, O11, O19, O25, O73 and O153) and seven sequence types (ST10, ST88, ST93, ST117, ST131, ST155, ST359, ST648 and ST1011). Interestingly, ST95, which is associated with the zoonotic potential of APEC and is spread in avian E. coli of North America and Europe, was not detected among 76 APEC strains. When the strains were clustered based on the presence of virulence genes, most ExPEC strains (71.7%) were contained in one cluster while most APEC strains (63.2%) segregated to another. In general, the strains showed distinct genetic and fingerprint patterns, but avian and human strains of ST359, or ST23 clonal complex (CC), presented more than 70% of similarity by PFGE. The results demonstrate that some zoonotic-related STs (ST117, ST131, ST10CC, ST23CC) are present in Brazil. Also, the presence of moderate fingerprint similarities between ST359 E. coli of avian and human origin indicates that strains of this ST are candidates for having zoonotic potential.