Experimental Pathology
and
Health Sciences
Research, Clinics, Teaching and Society
Journal of the Portuguese Experimental Pathology Association
Editor:
Associated Editors:
Editorial Board:
Redactorial Board:
António M. Silvério Cabrita, MD, PhD, Coimbra, Portugal
Manuel Luís Correia Matos Beja, MD, PhD, Coimbra, Portugal
Daniel Cartucho, MSci, MD, Faro, Portugal
António Silvério Cabrita, MD, PhD, Coimbra, Portugal
Américo Afonso, DMD, PhD, Porto, Portugal
Artur Varejão, DVM, PhD, Vila Real, Portugal
Aura Colaço, DVM, PhD, Vila Real, Portugal
Carlos A. Fontes Ribeiro, MD, PhD, Coimbra, Portugal
Carlos Gonçalves, MD, PhD, Coimbra, Portugal
Carlos Lopes, MD, PhD, Porto, Portugal
Carlos Viegas, DVM, PhD, Vila Real, Portugal
Fátima Gartner, DVM, PhD, Porto, Portugal
Fátima Martins, MD, PhD, Coimbra, Portugal
Felisbina Luisa Queiroga, PhD, Vila Real, Portugal
Fernanda Seixas Travassos, DVM, PhD, Vila Real, Portugal
Fernando Capela e Silva, PhD, Evora, Portugal
Fidel San Roman, DVM, PhD, Madrid, Spain
Francelina da Cruz Lopes, MD, PhD, Coimbra, Portugal
Graça Dias, DVM, PhD, Lisbon, Portugal
Helena Fernandes, PhD, Porto, Portugal
Isabel Dias, DVM, PhD, Vila Real, Portugal
Isabel Poiares Baptista, DMD, PhD, Coimbra, Portugal
Ivone Souza, PhD, Recife, Brasil
João A. B. Patrício, MD, PhD, Coimbra, Portugal
Jorge Colaço, DVM, PhD, Vila Real, Portugal
Jorge Rodrigues, DVM, PhD, Vila Real, Portugal
José A. S. Medeiros, MD, PhD, Coimbra, Portugal
José Manuel Almeida, DVM, Vila Real, Portugal
L. Boyanova, Sofia, Bulgaria
Luís Antunes, DVM, Vila Real, Portugal
Luis de la Cruz Palomino, DVM, PhD, Lugo, Spain
Margarida Caramona, PhD, Coimbra, Portugal
Maria de Lurdes Pinto, DVM, PhD, Vila Real, Portugal
Maria dos Anjos Pires, DVM, Vila Real, Portugal
Maria Helena Gil, PhD, Coimbra, Portugal
Maria João Pires, PhD, Vila Real, Portugal
Maria Manuela Estima Gomes, PhD, Minho, Portugal
Paula Oliveira, DVM, PhD, Vila Real, Portugal
Paula Pereira, PhD, Lisbon, Portugal
Paula Rodrigues, DVM, PhD, Vila Real, Portugal
Rita Payan Carreira, PhD, Vila Real, Portugal
Rogério Branco, MD, PhD, Porto, Portugal
Rui M. B. Alves, MD, PhD, Coimbra, Portgual
Stefano Geuna, MD, Turino, Italy
Vasco Bairos, PhD, Coimbra, Portugal
Rodrigo Farinha, DMD, Coimbra, Portugal
Ana I. V. Rafael, MSci, Coimbra, Portugal
Karen Cavalcanti, MSci, Recife, Brasil
Experimental Pathology and Health Sciences
Clinics, Teaching, Research and Society
Two issues each year
ISSN 1646-8414
Legal deposit: 266156/07
Founded: 2007
2008: Volume 2 (2)
Language: English
Correspondence:
António M Silvério Cabrita
Exinlab
Centro de Empresas de Taveiro
3000-111 Taveiro
Portugal
[email protected]
1
Experimental Pathology
Health Sciences
and
Research, Clinics, Teaching and Society
STATEMENT OF PURPOSE
As the beginning of a new century, there is a need to promote scientific and technological development applicable to the entire
community, only possible if research is primarily devoted to solving the basic problems and the financial gains are, instead of
being the goal, only the means to sustain research. Scientific knowledge and technological capacity should be translated into
practical applications for clinicians which in turn will be applicable to the population. New information and capacities can be
transferred to teaching programs to prepare new health technicians.
Experimental Pathology and Health Sciences
Journal belonging to the Portuguese Experimental Pathology Association
means to be a forum to bring together scientists, clinicians and those who can voice health social problems. Our objective is
to contribute to pluritranslational health work and in so doing provide better conditions for our citizens.
INSTRUCTIONS TO AUTHORS
Manuscript Categories
The journal comprises articles, organized under the following
subjects:
Editorial, History, Invited Opinion, Invited Review, Review,
Minireview, Reports, Student's Tribune, Technical Notes,
Research and Experimental Models, Clinical Cases, Clinics
and Society, Teaching in Health Science Courses, Student and
Research Matters, Applyed Technology.
All submissions should be made using the email address
[email protected]. All manuscripts are evaluated first by
the Editor and Associated Editors and then submitted to a
blinded peer-review process, where we preserve the confidentiality of the authors. After 60 days after the receiving date,
the authors are informed about the result of the review:
accepted, rejected of acceptable after some changes.
If there is any Conflict of Interest, the journal should be
informed by the author on the submission of the manuscript.
The Portuguese Association of Experimental Pathology
holds copyright of published papers.
All correspondence concerning editorial matters should be
addressed to:
António M Silvério Cabrita
Editor of Experimental Pathology and Health Sciences
Exinlab
Centro de Empresas de Taveiro
3000-111 Taveiro - Portugal
or by email to: [email protected].
Manuscript Structure
Manuscripts should be prepared in the style of the Journal
and according to the Uniform Requirements for Manuscripts
Submitted to Biomedical Journals (Available at: http://www.icmje.org).
Reviews should have a maximum of 8,000 words, 150 references, and six tables or figures.
First Page: Should contain an intelligible to the general reader abstract, with no more than 250 words. For research papers
the abstract should clearly summarize the background,
methodology, results and their significance.
Second Page: The second page must include a concise title;
complete names of all authors; departments, institution and
address where the research was performed; grant numbers
and sources of support; name, address, e-mail and fax of the
corresponding author. Any affiliations with any organization
or entity having a direct financial or personal interest in the
subject matter or materials discussed in the article should also
be stated. The title page is the only page where the authors
and their affiliations are identified. Please refer the number of
text
2
pages, tables and figures of the manuscript.
Body Text: Starts on the third page of the manuscript. For
research papers the remaining sections of the text, should
include: Introduction, Materials and Methods, Results,
Discussion, and Acknowledgments. Commonly abbreviated
terms should be spelled out in their first occurrence and then
may be referenced in abbreviation through the remainder of
the manuscript. Authors must say if the appropriate boards or
ethics committee approved the research protocol. If applicable authors should inform about the existence of informed
permission of the patients.
Tables: Tables should be typed double-spaced and submitted
on separate pages, as part of the manuscript. Tables should be
black and white text only and should not include figures or
other non-typeset images.
Figures: One figure consists on one or multiple related panels described under one legend. During the paper construction, figures will be sized to fit one or two columns. Figures
without the appropriate size will be sized at the publisher's discretion. If the exact scale is critical, scale bars should be used
on the photograph and specified in the legend. The legends
are submitted as part of the manuscript, in the place where the
related figure should appear in the paper . An adjustment of
brightness, contrast, or color balance is only acceptable if
applied to the whole image and does not change the conclusions taken from the picture. All pictures should be sent separately, in JPEG or TIFF format, with the best resolution possible.
References
References should be double-spaced and numbered in order
of citation in the text, including citations in tables and figure
legends. Complete author citation is required. References
should conform to the style of the Journal, as follows (examples):
References of Journals: Pereira JE, Cabrita AM, Filipe VM,
Bulas-Cruz J, Couto PA, Melo-Pinto P, Costa LM, Geuna S,
Mauricio AC, Varejao AS. A comparison analysis of hindlimb
kinematics during overground and treadmill locomotion in
rats. Behav Brain Res. 2006:172; 212-218
References of Books: Ted A. Looms, A. Wallace Hayes.
Numbers in Toxicology. Loomis's Essentials of Toxicology.
Edited by Academic Press. 1996; pp.17-30
References of Websites: Cited in text only. Include the name
of the institution sponsoring the web site, URL address and
date of access.
Authors will receive an electronic (PDF) reprint.
Experimental Pathology and Health Sciences
5
EDITORIAL
Science and Goodwill for Health Care
António M. Silvério Cabrita
2008: 2(2)
OPINION
7 A Regenerative Approach for Cancer Treatment and Understanding
António M. Silvério Cabrita and Manuel C. de Matos Beja
MINIREVIEW
9 Muscle Regeneration
António Cabral, Vanessa Machado, Nuno Machado and Rodrigo Farinha
REPORT 2008
19 Food For Health
HISTORY - INTEMPORAL DOCTORS
21 Zhang Zhongjing
Catarina Amaro
RESEARCH PAPERS
23 Comparison of Animal Models for the Study of Inflammation
Maria dos Anjos Pires, Filomena Adega, Rita Payan-Carreira, Fernanda Seixas, Fernando Oliveira-Torres
27 Inhibition of Serotonin-induced Contractions of Guinea-pig Ileum by Tilia europeae L.
Aqueous Extract
M. Dulce Cotrim, Isabel Vitória Figueiredo, T. Baptista, Carlos A. Fontes Ribeiro
31 Bowel Mucosa-associated Lymphoid Tissue in Experimental Red Wine, De-alco-
holized Red Wine, Ethanol and DMH Administration
Tiago F. Rama, Isabel S. Carneiro, Ana Rita P. Fonseca, José C. B. Silva, Karen Cavalcanti and António
M. Silvério Cabrita
39 Assessment of the Cytotoxicity of Microparticles for Controlled Drug Release in
Oftalmology
Ana Cristina Santos, Cláudia Matos, Rosemeyre Cordeiro, Ana Rita Brás, Bárbara Oliveiros, Elisa
Campos, Patrícia Alves, Maria Graça Rasteiro, Maria Helena Gil
CLINICAL CASES
45 Use of Intratumural Cisplatin in Lung Cancer
Daniel Cartucho.......
STUDENT AND RESEARCH MATTERS
47 Basic Indexes for Small Rodents in Experimental Pathology
António M. Silvério Cabrita, Rodrigo Farinha, Karen Cavalcanti, Ana Calado, Pedro Barreto and M.L.
Matos Beja
51 Allergy Diagnosis - an Application to Dog
Luís M.L. Martins, Ana Goicoa Valdevira, Juan Rejas López
61 Workshop in Pharmaceutical and Biomedical Sciences - Programme
Abstracts of Oral Presentations
71 News
Rat tooth germen
H&E; 100X in the original
3
4
OPINION
Experimental Pathology and Health Sciences
2007; 2 (2): zzzzz
A Regenerative Approach for
Cancer Treatment and
Understanding
António M. Silvério Cabrita and Manuel C. de Matos Beja
Figure 1. ...........
António M. Silvério Cabrita MD, PhD,
Faculty of Medicine of Coimbra’s University,
President of the Portuguese Experimental
Pathology Association
[email protected]
M. L. Matos Beja MD, PhD
Portuguese Experimental Pathology
Association
For many years we have been accepting a unified theory of carcinogenesis, the classical explanation that divides the process in
three sequential basic steps. During the last decades an increasing
number of molecular studies on carcinogenesis have demonstrated
that neoplasm may arise from several different ways and so, being
actually different entities. If this is the case, a different approach
for cancer prevention and treatment may be needed.
It is not to exclude that many neoplasm may have their origin in
non mature cells, which by malignant transformation show several
properties of active stem cells (1-10). A new hypothesis has been
introduced which indicates that neoplastic cells may be originated
in stem cells and that cancer cells with stem cell characteristics may
be identified in neoplastic lesions. In this case instead of trying to
kill these cells the treatment approach could be directing them to a
normal differentiation process. If we assume that at least some
neoplastic cells are transformed into malignant stem cells it would
be a possible therapeutic choice to induce dedifferentiation of
these cells and then to direct the rededifferentiation to a normal
and stable phenotype. Also it should be a priority to understand
what cell group or niche in each tissue is the possible target for carcinogenesis etiologic factors.
It is said that cancer stem cells only represent a minor tumoral cell
population and that this number only represents those that have been identified up
until now. It is now supposed that only cancer
stem cells are responsible
for the capacity to propagate tumor transplanted
into nude mice (8,9).
Several studies
describe a series of events
that bench mark the
beginning of the complex
process, in various stages,
of carcinogenesis. Even
though It is not yet clear,
recent data points to stem
cells as the possible target
of this process, possibly Figure 2. ...........
while in a susceptible
stage with already some
degree of maturation
(11,12) (Figure1). The
5
cells subject to this process should have their dedifferentiation capacity on a normal mature tissue blocked
and their proliferation capacity stimulated. In this case
the process of malignant transformation would initially affect the balance between the forces that point
towards maturation and the forces that stimulate pro- Figure 3. ...........
liferation (Figure 2). On a next stage, the cell having its
dedifferentiation system affected would come to
express molecules that could correspond to different
stages of the dedifferentiation of its respective original
tissue or even another type of tissue, in what we can
call of molecular anachronism (Figure 3). This plastic
capacity and of adaptation to the envolving environment would allow the transformed cells to adapt, survive and proliferate. If this is infact the process, then
the treatment of neoplastic lesions could be regarded
as a group of procedures that would restitute the
capacity of maturation and that would naturally
oppose to proliferative activity. In this case treatment
should succeed with chemical stimuli capable of directioning maturation, consequently silencing the proliferative process (Figures 4 and 5), a therapeutic approach
by reprogramming tumoral cell which is now done in
some conditions (13,14). Similar to what we do in vitro Figure 4. ...........
with stem cell cultures, in a first stage we expand and
in the second we direct maturation which happens
through mechanisms that reduce or suppress cell proliferation.
References:
1. Pitot HC and Dragan YP. Facts and Theories concerning the
mechanisms of carcinogenesis. The Faseb Journal. 1991:5;22802286.
2. Sell, S and Pierce GB. Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinomas
and epithelial cancers. Lab. Invest. 1994:70;6-22
3. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer,
and cancer stem cells. Nature. 2001 Nov 1;414(6859):105-11.
4. Behbod F and Rosen JM. Will cancer stem cells provide new therapeutic targets?. Carcinogenesis. 2004:26;703-711
5. Woodward WA, Chen MS, Behbod F and Rosen JM. On mammary stem cells. Jounarl of Cell Science. 2005:118;3585-3594
6. Tai M-H, Chang C-C, Olson LK and Trosko JE. Oct4 expression
in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis. 2005:26;495-502
7. Vermeulen L, Sprick MR, Kemper K, Stassi G, Medema JP. Cancer Figure 5. ...........
stem cells--old concepts, new insights. Cell Death Differ. 2008
Jun;15(6):947-58
8. Hart LS, El-Deiry WS.. Invincible, but not invisible: imaging approaches toward in vivo detection of cancer stem cells. J Clin Oncol. 2008 Jun 10;26(17):2901-10.
9. Gsteiger S, Morgenthaler S. Heterogeneity in multistage carcinogenesis and mixture modeling. Theor
Biol Med Model. 2008 Jul 21;5:13.
10. Ashkenazi R, Gentry SN, Jackson TL. Pathways to tumorigenesis--modeling mutation acquisition in
stem cells and their progeny. Neoplasia. 2008 Nov;10(11):1170-82.
11. Ye F, Zhou C, Cheng Q, Shen J, Chen H. Stem-cell-abundant proteins Nanog, Nucleostemin and
Musashi1 are highly expressed in malignant cervical epithelial cells. BMC Cancer. 2008 Apr 18;8:108.
12. Sotomayor P, Godoy A, Smith GJ, Huss WJ. Oct4A is expressed by a subpopulation of prostate neuroendocrine cells. Prostate. 2008 Dec 3
13. Bru T, Clarke C, McGrew MJ, Sang HM, Wilmut I, Blow JJ. Rapid induction of pluripotency genes after
exposure of human somatic cells to mouse ES cell extracts. Exp Cell Res. 2008 Aug 15;314(14):2634-42.
14. Cabral AJ, Machano V, Machado NV, Farinha R. Reversine: A New Promising Compound.
Experimental Pathology and Health Sciences. 2008; 1 (1): 13-22.
6