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The role of the NO-cGMP pathway as a putative target in antidepressant action / Renché RetiefRetief, Renché January 2004 (has links)
Depressive disorders are among the most frequent psychiatric diseases in the Western world
with prevalence between 9% and 18%. Poor compliance and inappropriate antidepressant
discontinuation invokes long-term morbidity, and appear linked to hippocampal shrinkage.
Despite major advances in pharmacological treatment of the illness over the past 3040 years,
currently available agents have distinct shortfalls both in clinical efficacy and in maintenance of
response. This implies a greater long-term morbidity with significant impact on the patient, the
patient's family as well as economic implications to health care managers and providers. The
major reason for this state of affairs is our poor understanding of the neurobiology of depression
and hence, of antidepressant (AD) action. AD drugs are thus not addressing the crucial
neurobiological target underlying the illness, and new strategies and treatments are urgently
needed. In recent years, depression has been associated with disturbances in excitotoxic
glutamatergic activity, yet this has not been systematically evaluated.
While the role of neurotransmitters such as serotonin, noradrenaline and dopamine has been
extensively studied, new evidence suggests a role for the unique neurotransmitter nitric oxide
(NO). Nitric oxide (NO), is activated by glutamatergic systems in various limbic and other
regions of the brain, and has recently also been implicated in anxiety and affective disorders. Of
special interest is the putative role of NO in cellular memory, synaptic plasticity and cell survival,
all-important processes in the neuropathology and neurodevelopment of depression.
Recent clinical studies have provided evidence of the role of the NO-pathway in depression,
while preclinical studies have demonstrated the anxiolytic and antidepressant actions of nitric
oxide synthase (NOS)-inhibitors. Moreover, NO interacts with other classical transmitters that
have a regulatory role on mood, particularly the monoamines, as well as glutamate and gammaaminobutyric
acid (GABA).
In the current study the role of the NO-cGMP pathway in AD action was investigated, after
chronic imipramine (IMI) and after IMI withdrawal, using a learned helplessness paradigm.
Behavioural changes, hippocampal NOS activity and cGMP accumulation was determined
together with pharmacological manipulation of the NO-cGMP pathway.
Chronic IMI, 15 mg/kg/day intraperitoneal (ip) administration induced a pronounced reduction in
swim immobility time in the forced swim test (FST), with no effect on horizontal or vertical
locomotor activity. These behavioural changes were accompanied by a significant reduction in
NOS enzyme activity and cGMP accumulation. In order to confirm the involvement of the NO-cGMP
pathway in the AD action of IMI, chronic (3 weeks) IMI treatment was followed by an
acute withdrawal of 7 days. Acute withdrawal, after chronic IMI treatment, resulted in a
significant increase in swim immobility time and an increase in NOS enzyme activity and cGMP
levels. In fact, NOS activity was raised above that of control, not just higher than the effect of
chronic IMI.
In order to assess the possible role of the NMDA-NO-cGMP pathway in AD withdrawal, the
NMDA receptor antagonist, memantine, and the NOS/guanylyl cyclase (GC) inhibitor,
methylene blue (MB), were administered during the 7 day IMI withdrawal period.
Memantine (5 mg/kg/d ip), during the 7 day IMI withdrawal period, significantly reversed the
increase in immobility time evoked after IMI withdrawal. This was accompanied by a significant
reduction in NOS enzyme activity and a tendency to decrease cGMP levels. This data confirms
that the antidepressant action of IMI, as well as IMI withdrawal, is associated with actions on the
NMDA-GIu-NO-cGMP pathway. Particularly. IMI withdrawal evokes an increase in glutamate
activity that is responsible for NOS activation.
During the 7 day IMI withdrawal period, MB (15 mg/kg/d ip) also significantly reversed the
increased immobility time after IMI withdrawal and was accompanied by a tendency to decrease
NOS enzyme activity and cGMP levels in the rat hippocampus, however statistical significance
was not reached. Although not emphatic, this data implies a possible role of the NO-cGMP
pathway in AD action and AD withdrawal.
In order to determine whether the observed IMI withdrawal effects on the NO-cGMP pathway
may occur through an initial destabilisation in the serotonergic system, the 5-HT2a/2c receptor
antagonist, ritanserin (4 mg/kg/d ip), was administered during the IMI withdrawal period.
These studies revealed that antidepressant withdrawal evokes an increase in 5-HT2-mediated
activity, and that antidepressant-induced NOS activation after withdrawal has its origin in
serotonergic hyperactivity. Clearly, this is supportive of a distinct relationship between the NO
and serotonergic system in antidepressant response. On its own, ritanserin was found to
increase NOS and cGMP levels, yet during IMI withdrawal this response was lost, suggesting
that IMI withdrawal alters the response to a 5-HT2a/2c receptor antagonist, which may have major
clinical implications.
In conclusion, the AD action of IMI, as well as chronic IMI withdrawal, involves actions on the
NO-cGMP pathway. Withdrawal of ADS is associated with a loss of AD efficacy together with an
increase in release of NO and cGMP. The NMDA antagonist, memantine, and the NOS/GC
inhibitor, MB, reversed these responses therefore suggesting that the NMDA-GIu-NO-cGMP
pathway may be a new putative target in understanding the neurobiology of AD action. Finally,
NOS activation following withdrawal suggest that inappropriate withdrawal during the treatment
of depression may mediate neurodegenerative pathology observed in recurrent depression,
possibly by severely increased hippocampal NOS activity which is toxic to neurons. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2005.
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Sex Differences in Cardiac and Cerebral Damage after Hypovolemic Cardiac ArrestSemenas, Egidijus January 2011 (has links)
Resuscitation from haemorrhagic shock and the subsequent circulatory arrest remains a major clinical challenge in the care of trauma patients. Numerous experimental studies in sexually mature animals have shown a gender dimorphism in response to trauma and haemorrhagic shock. The first study was designed to evaluate sex differences in outcome after resuscitation from hypovolemic circulatory arrest. We intended to examine innate sex differences, and chose to study sexually immature animals. The study showed that cerebral cortical blood flow was greater, blood-brain-barrier was better preserved and neuronal injury was smaller in female as compared to male piglets. The second study demonstrated that female sex was associated with enhanced haemodynamic response, cardioprotection, and better survival. This cardioprotective effect was observed despite comparable estradiol and testosterone levels in male and female animals, indicating an innate gender-related cardioprotection. In both studies (I and II) female sex was associated with a smaller increase in the cerebral expression of inducible and neuronal nitric oxide synthase (iNOS and nNOS). Thus in the study III we tested the hypothesis that exogenously administered 17β-estradiol (E2) could improve neurological outcome by NOS modulation. The results showed that compared with the control group, animals in the E2 group exhibited a significantly smaller increase in nNOS and iNOS expression, a smaller blood-brain-barrier disruption and a mitigated neuronal injury. There was also a significant correlation between nNOS and iNOS levels and neuronal injury. A hypothesis if female-specific cardioprotection may be attributed to a smaller NOS activity was tested in study IV. The animals received methylene blue (MB) during CPR, but were otherwise treated according to the same protocol as studies I-II. The female-specific cardioprotection could be attributed to a smaller NOS activity, but NOS inhibition with MB did not improve survival or myocardial injury, although it abated the difference between the sexes.
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Strategies of neuroprotection in an in vivo model of retinal degeneration induced by mitochondrial dysfunctionRojas-Martinez, Julio Cesar. January 1900 (has links)
Thesis (Ph. D.)--University of Texas at Austin, 2009. / Title from PDF title page (University of Texas Digital Repository, viewed on Sept. 9, 2009). Vita. Includes bibliographical references.
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Avaliação da atividade antimicrobiana da terapia Fotodinâmica sobre a inativação de espécies do gênero Candida: estudo in vitroQueiroga, Andréa Sarmento 19 August 2010 (has links)
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Previous issue date: 2010-08-19 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Candida species are part of the commensal microbiota of the oral cavity of most
healthy individuals. The emergence of new species of Candida and the selection of
lines tolerant to conventional antifungal agents stimulates the development of new
therapies for the treatment of infections caused by species of Candida. In this context
stands the photodynamic therapy (PDT) which is capable of killing fungal cells by
administration of a photosensitizing substance followed by the application of light in
the visible wavelength. This study evaluated, in vitro, the efficacy of PDT in
photoinactivation of Candida species (C. albicans, C. krusei, C. tropicalis and C.
guilhermondii) using the photosensitizing agent methylene blue (150μg/ml) and
irradiation with a diode laser operating in the visible red (ʎ660nm, 40mW). Initially,
the tested microorganisms were inoculated in test tubes containing liquid culture
medium and incubated overnight at 37°C. Then cell s uspensions were obtained
containing 106 cfu / ml. These suspensions were transferred to 96-holes plates and
exposed to 03 doses of laser light (Group 1- 60J/cm2 (2,4J), Group 2- 120J/cm2
(4,8J), Group 3-180J/cm2 (7,2J)). Additional suspensions were treated with only the
photosensitizer, with only the laser light or with 0.85% saline (control group). Each
experimental condition was performed twice. After the treatments, 1μl aliquots of the
suspensions were plated on Sabouraud Dextrose Agar. The plates were incubated at
37°C for 24-48h and after this period there was the counting of colonies (cfu / ml).
The three doses evaluated determined significant inactivation of Candida spp. (P
<0.05). The 180J/cm2 dose was the most effective, inactivating 78% of cfu/ml
followed by doses of 120J/ cm2 and 60J/cm2 with inactivation average of 62% and
42% respectively. A statistically significant difference between the rates of
inactivation of C. albicans, C.krusei, C. tropicalis and C. guilhermomdii at doses of 60
J/cm2 and 120 J/cm2 (p> 0.05) was not verified. However, at a dose of 180 J/cm2 C.
albicans was the most susceptible species to the effects of PDT. We conclude that
photodynamic therapy (PDT) has demonstrated effectiveness in the inactivation of
Candida spp. / As espécies de Candida fazem parte da microbiota comensal da cavidade bucal da
maioria dos indivíduos saudáveis.. A emergência de novas espécies de Candida e a
seleção de linhagens tolerantes aos antifúngicos convencionais estimula o
desenvolvimento de novas modalidades terapêuticas para o tratamento das
infecções causadas por espécies de Candida.Nesse contexto destaca-se a terapia
fotodinâmica (TFD) que é capaz de eliminar células fúngicas através da
administração de uma substância fotosensibilizadora seguido da aplicação de luz em
comprimento de onda visível e compatível. Este estudo avaliou, in vitro, a eficácia da
TFD na fotoinativação de espécies do gênero Candida (C. albicans, C. krusei, C.
tropicalis e C. guilhermondii) por meio do agente fotossensibilizador azul de metileno
(150μg/ml) e da irradiação com um Diodo Laser (660nm, 40mW)). Inicialmente os
microrganismos avaliados foram inoculados em tubos de ensaio contendo meio de
cultura líquido e incubados overnight a 37°C. Em seguida foram obtidas suspensões
celulares contendo 106 ufc/ml, as quais foram transferidas para placas de 96 orifícios
e expostas a 03 doses de luz Laser (Grupo1- 60J/cm2 (2,4J), Grupo2- 120J/cm2
(4,8J), Grupo 3-180J/cm2 (7,2J). Suspensões adicionais foram tratadas apenas com
o fotossensibilizador, apenas com a luz Laser ou com solução salina 0,85% (grupos
controle). Cada condição experimental foi realizada 2 vezes. Após a aplicação dos
tratamentos, alíquotas de 1μl das suspensões foram plaqueadas em Agar
Sabouraud Dextrose. As placas foram incubadas a 37°C por 24-48h e após esse
período foi realizada a contagem das colônias (ufc/ml). As três doses avaliadas
determinaram inativação significativa de Candida spp. (p<0,05). A dose de 180J/cm2
foi a mais eficaz, inativando 78% das ufc seguida pelas doses de 120J/ cm2 e
60J/cm2 com inativação média de 62% e 42% respectivamente. Não foi verificada
diferença estatística significativa entre as taxas de inativação de C.albicans,
C.krusei, C. tropicalis e C. guilhermomdii nas doses de 60 J/cm2 e 120 J/cm2 (p>
0,05). No entanto, na dose de 180 J/cm2 C. albicans foi a espécie mais susceptível
aos efeitos da TFD. Conclui-se que a terapia fotodinâmica (PDT) demonstrou
efetividade na inativação de Candida spp.
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Improving Evaporation Rate of Mine WastewaterKhumalo, Londiwe Thandeka Precious January 2018 (has links)
Magister Scientiae - MSc (Biotechnology) / The treatment of mine water at the eMalahleni Water Reclamation Plant (EWRP) results in the
production of large volumes of brine. Different brine management methods have been applied
to dispose the brine but the evaporation pond method is regarded as the cheaper, most effective
and less laborious method for brine disposal. Brine wastewater is pumped into the pond where
it evaporates resulting in the mixture of salts. The rate at which evaporation occurs is influenced
by many factors such as temperature, salinity, humidity and wind. Due to high salinities in
brine the EWRP is currently experiencing a challenge with low evaporation rate. Here, a
comparative study was done to determine the efficiency of using a chemical and a biological
approach to enhance the evaporation rate of reject brine. The chemical approach involved the
addition of various concentrations of methylene blue dye (100 to 300 ppm with 50 ppm
increments) to 1L volumes of brine, and measuring the evaporation rate. On the other hand, the
biological approach involved the isolation of pigmented halophilic bacteria from eMalahleni
brine and Cerebos salt samples. Isolated bacterial strains were characterised based on their
morphology, biochemical and salt tolerance characteristics. Furthermore, the strains were
identified using 16S rRNA gene sequence analysis. Among the isolated halophilic bacterial
strains, EP-3, an Arthobacter agilis isolated from the eMalahleni brine produced a darker
pigment compared to the other strains. Therefore, EP-3 was evaluated for its effect on the
evaporation of brine using a culture inoculum or the addition pigment extracted from an EP-3
culture. The addition of MB above 100 ppm overcame the effect of salt precipitation and
resulted in higher evaporation (41%) rate. Addition of pigmented bacteria or bacterial extracted
pigment to the brine respectively resulted in 18% and 24% increase in the evaporation rate.
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O papel do óxido nítrico na patogênese da leptospirose experimental em hamsters e camundongosSantos, Cleiton Silva January 2014 (has links)
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Previous issue date: 2014 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / A patogênese da leptospirose é pouco compreendida e os estudos com
enfoque na resposta inflamatória sistêmica ou local são escassos, em especial no
que se refere ao papel do óxido nítrico (NO) e da enzima óxido nítrico sintase
induzível (iNOS). Dados de ensaios em culturas de células renais sugerem um
papel importante da liberação de mediadores inflamatórios, tais como NO, na
resposta às leptospiras e consequente nefrite intersticial. A transposição destes
achados para o modelo in vivo foi pouco explorada. Por outro lado, estudos em
humanos sugerem que a liberação sistêmica de NO correlaciona-se com a
gravidade da doença renal e, portanto, pode ser um potencial alvo para terapia
adjuvante à antibioticoterapia. O presente trabalho estudou a correlação da iNOS
com distúrbios hidroeletrolíticos na patogênese da leptospirose. No modelo
experimental de hamsters, avaliamos a associação da inibição dos efeitos do NO,
através da terapia combinada de antibioticoterapia padrão e azul de metileno, com
distúrbios eletrolíticos, alterações histopatológicas em hamsters e sobrevida.
Nenhum benefício da terapia adjuvante com azul de metileno foi demonstrado. No
modelo de camundongos transgênicos, investigamos o efeito da ausência do gene
da iNOS na nefrite intersticial e na quantidade de bactérias observadas nos tecidos.
A ausência do gene iNOS esteve associado a menor frequência de nefrite
intersticial grave. Maiores estudos são necessários para investigar a função da
inibição da produção de NO na patogenia da doença e da nefrite associada a
leptospirose. / The pathogenesis of leptospirosis is poorly understood, and there are few studies
fusing on the systemic or local inflammatory responses, especially referring to the role
of nitric oxide (NO) and the enzyme inducible nitric oxide synthase (iNOS). Data from
in vitro studies suggest an important role of inflammatory mediators, such as NO, in
the response to leptospires in the development of interstitial nephritis. The
transposition of these findings to an in vivo model was little explored. However, studies
in humans suggest that systemic liberation of NO is correlated with severity of renal
disease and therefore can be potential target to adjuvant therapy along with antibiotic
therapy. The present work evaluated the correlation of iNOS with the pathogenesis of
leptospirosis. In the experimental hamster model, we evaluated the effect of inhibiting
downstream effects of NO on electrolytic disorders, histopathological changes and
survival. No benefit of methylene blue treatment could be observed when compared to
antibiotic (ampicillin) therapy only. In the mouse transgenic model, we investigated the
effect of the absence of the Inos gene in interstitial nephritis and in the bacterial burden
in target tissues. The absence of a functional iNOS gene was associated with lower
frequency of severe interstitial nephritis.
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Avaliação dos efeitos da terapia fotodinâmica utilizando compostos fenotiazínicos sobre melanoma in vitroMiranda, Anderson Fontes Suzart January 2015 (has links)
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Previous issue date: 2015 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / O câncer é considerado a segunda maior causa de morte em países ocidentais. Nos Estados Unidos da América (EUA) as mortes por câncer anualmente superam a soma das mortes provocadas em guerras como Vietnã, Coreia e as Grandes Guerras Mundiais. Apresentando-se como a mais agressiva das neoplasias dermatológicas, o melanoma cutâneo está associado à cerca de 75% das causas de morte por câncer de pele. Um dos tratamentos estudados para aplicação em pacientes com esta e outras patologias é a Terapia Fotodinâmica (TFD), que é baseada no uso de corantes de baixa toxicidade, que tem seletividade por alguns tecidos ou células e quando ativados por baixas doses de luz visível induzam alterações celulares como a produção ERO. Os fenotiazínicos são moléculas catiônicas com, absorção de luz na região entre 620-660nm, espectro que permite maior penetração nos tecidos, promovendo maior ação do composto em tecidos mais profundos. A irradiação foi feita com luz lazer com λ= 660nm, com potência de 100 mW, densidade de energia de 150 J/cm2 por 1 min. As quantificações de viabilidade celular foram feitas por método colorimétrico, e realizada a leitura em leitor de microplaca a 655 nm. A determinação das IC50 do Azul de Metileno e Azul de Toluidina O foi 2,5 μM e 8,4 μM, respectivamente. Utilizando a TFD observamos que os efeitos citotóxicos dos compostos fenotiazínicos apresentam significância estatística (p<0,05) tanto em AM quanto em ATO. Em microscopia óptica com coloração por May-Grunwald-Giemsa observamos que existe uma aparente diminuição do conteúdo citoplasmático e preservação nuclear nas células tratadas com TFD, além da diminuição da quantidade de células por campo. A avaliação ultraestrutural por Microscopia de varredura mostra células com visível extração citoplasmática após a TFD, apontando uma lesão membranar. Novas avaliações precisam ser feitas como estabelecer um melhor protocolo para aumentar os efeitos da TFD. / Cancer is considered the second leading cause of death in Western countries. In the United States of America (USA) cancer deaths annually exceed the total of deaths in wars like Vietnam, Korea and the Great World Wars. Presenting as the most aggressive of the skin neoplasms, cutaneous melanoma is associated with circa 75% of the deaths from skin cancer. One of the therapies used in patients with melanoma and other pathologies is Photodynamic Therapy (PDT), which is based upon the use of dyes of low toxicity, which has selectivity for certain tissues or cells and low doses when activated by visible light induce cellular changes such as ROS production. The phenothiazic dyes are cationic molecules, absorption of light in the region between 620-660 nm, allowing greater spectrum tissue penetration, promoting higher activity of the compound in deeper tissues. The irradiation was performed with laser light with λ = 660 nm with 100 mW, energy density of 150 J/cm2 for 1 min. Quantification of cell viability was performed by the colorimetric method, and performed a reading in a microplate reader at 655nm. Determination of IC50 of Methylene Blue and Toluidine Blue O was 2.5 μM and 8.4 μM respectively. Using the protocol of PDT observed that there is one of the cytotoxic effects of phenothiazine compounds with statistical significance (p <0.05) in both MB and in TBO. Through optical microscopy by staining with fast Panotic was observed that there is an apparent decrease in the cytoplasm in cells treated with MB and TBO as well as reduced number of cells per field. The Scanning Electron Microscopy, shows cells with cytoplasm extraction, after PDT, indicated possibility, membrane damage. New assessments need to be made to establish a better protocol to potentiate the effects of PDT.
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Influência dos corantes Azul de Metileno a 2% e Rodamina B a 2% na determinação da capacidade seladora apical de diferentes cimentos endodônticosSouza, Erick Miranda [UNESP] 30 March 2004 (has links) (PDF)
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souza_em_me_arafo.pdf: 1650623 bytes, checksum: 97003cfd54c5042d5a5a6e21f97e5ffc (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Banca: Idomeo Bonetti Filho / Banca: Marco Antônio Húngaro Duarte / A proposta deste trabalho foi comparar os níveis de infiltração apical determinados pelos corantes azul de metileno a 2% e Rodamina B a 2% em canais radiculares obturados com cimentos endodônticos de diferentes composições químicas. Foi também determinada a capacidade seladora apical dos cimentos Endofill, Sealer 26, AH Plus, Sealapex, EndoREZ e um cimento experimental à base de polímero de mamona (Polifil) em cada solução corante. Foram utilizados 176 dentes unirradiculares extraídos de humanos que foram instrumentados com limas do Sistema K3 de conicidade 0,04mm/mm e obturados pela técnica da condensação lateral modificada utilizando-se um cone principal de conicidade 0,04mm/mm e dois cones auxiliares. As raízes foram divididas em grupos de acordo com o cimento obturador utilizado e estes novamente divididos em subgrupos de 14 dentes cada de acordo com a solução corante a ser utilizada como traçador da infiltração. Oito dentes foram utilizados como controle sendo 4 controles positivo e 4 controles negativo. As raízes foram impermeabilizadas em toda superfície radicular externa com exceção do forame apical e submetidas à infiltração nas duas soluções corantes, em um ambiente de vácuo por 24 horas. Foram mensuradas as infiltrações apicais por meio do programa ImageTool for Windows versão 3.0 e os resultados submetidos à análise estatística pelos testes ANOVA, t-Student e Newman-Kells. Verificou-se que os níveis de infiltração determinados pelas soluções corantes dependem de qual cimento é avaliado. A solução de azul de metileno a 2% determinou nos cimentos Endofill, Sealer 26 e Sealapex menores níveis de infiltração que os determinados pela Rodamina B nos mesmos cimentos, sugerindo uma incapacidade da solução de azul de metileno a 2% em revelar a totalidade da falha da obturação realizada com estes cimentos... . / The purpose of this study was to compare the levels of apical leakage determined by the 2% methylene blue and 2% Rhodamine B dyes in root canals filled with endodontic sealers of different chemical compositions. It was also determined the apical sealing ability of the sealers Endofill, Sealer 26, AH Plus, Sealapex, EndoREZ and an experimental sealer based on castor oil polymer (Polifil) in each dyeing solution. It was used 176 single root teeth extracted from humans that were instrumented with K3 system files taper .04 and filled by the modified lateral condensation technique using a main cone taper .04 and two auxiliary cones. The roots were divided in groups according to the filling sealers that were used and these ones were divided again in subgroups of 14 teeth each one according to the dyeing solution used as infiltration tracer. Eight teeth were used as control group, four positive controls and 4 negative controls. The roots were impermeabilized on all external root surface, excepting for the apical foramen, and subjected to the infiltration into the two dye solutions in a vacuum environment for 24 hours. The apical leakage were measured by means of the software ImageTool® for Windows version 3.0 and the results were subjected to statistical analysis by the tests ANOVA, t-Student and Newman-Kells. It was noticed that the levels of leakage determined by the dye solutions depend on which sealer is evaluated. The 2%methylene blue solution in the sealers Endofill, Sealer 26 and Sealapex presented lower levels of leakage compared to the ones determined by 2% Rhodamine B in the same sealers, suggesting that 2% methylene blue dye is unable to determine the total extension of the leakage in those sealers. The other sealers did not present significant differences in the apical leakage levels determined by both dye solutions. In relation to the apical sealing... (Complete abstract, click electronic address below).
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Estudo da dinâmica de fotodegradação e agregação das fenotiazinas azul de metileno e azul de orto-toluidina com relação a eficiência fotodinâmicaNUNEZ, SILVIA C. 09 October 2014 (has links)
Made available in DSpace on 2014-10-09T12:53:17Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:09:35Z (GMT). No. of bitstreams: 0 / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP
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Mecanismos da terapia fotodinâmica em presença de peróxido de hidrogênioGARCEZ SEGUNDO, AGUINALDO S. 09 October 2014 (has links)
Made available in DSpace on 2014-10-09T12:53:35Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:09:32Z (GMT). No. of bitstreams: 0 / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energéticas e Nucleares - IPEN-CNEN/SP
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