A trajetória de mulheres com câncer de mama: uma proposta de estudo sobre prática avaliativa de integralidade no município de Volta Redonda

Esta pesquisa objetivou compreender o itinerário terapêutico de quatro mulheres com câncer de mama, no que concerne à trajetória assistencial na busca por cuidado no SUS de Volta Redonda, procurando perceber em que medida elas tiveram suas necessidades, relacionadas ao processo de adoecimento, atendidas pelos serviços de saúde, tendo como eixo norteador a integralidade em saúde. O objeto do estudo foi construído a partir do entendimento do câncer de mama como um problema de saúde pública, da contextualização do programa de controle do câncer de mama e da reflexão sobre avaliação, integralidade e itinerários terapêuticos como prática avaliativa no campo da saúde. Como trajetória metodológica, para o alcance dos objetivos propostos, a opção foi desenvolver um estudo de natureza qualitativa, empregando a história de vida como abordagem central. Nesta perspectiva, para o trabalho investigativo e interação com as quatro mulheres, visando à narrativa de suas experiências, foi utilizada a técnica de entrevista aberta na coleta de dados, com ênfase na etapa da vida após a descoberta do câncer de mama e a busca de cuidado nos serviços de saúde. As entrevistas, complementadas pelos dados dos prontuários e do diário de campo, constituíram- se como o material empírico para proceder às análises, visando, sobretudo, a apreender os atributos de integralidade na dimensão da organização dos serviços de saúde e nos conhecimentos e práticas dos profissionais de saúde. Também se buscou analisar o cumprimento dos objetivos do Programa Nacional de Controle do Câncer de Mama, em Volta Redonda, tendo em vista que as ações aí propostas representam um conjunto de prescrições para reversão da atual situação da doença no país. Pode-se evidenciar, nas análises, que o cuidado em saúde dedicado a essas mulheres com câncer de mama está muito distante do princípio da integralidade que nos orienta e que defendemos como bandeira de luta. Nesse sentido, são várias as pistas nas narrativas que nos levam a afirmar que os serviços e práticas profissionais não estão organizados para proteger essas mulheres, garantindo as respostas necessárias a suas demandas, pautadas no princípio da integralidade e nos direitos e valores relacionados à defesa da vida humana. Percebe-se um quadro de retardamento do diagnóstico e tratamento, com dificuldade no acesso a diversos procedimentos envolvidos nesse cuidado como exemplos, a mamografia, o resultado do exame histopatológico e a cirurgia de mama. O exame clínico da mama não é realizado ou valorizado na atenção básica, além de que, as práticas das unidades especializadas continuam centradas na atenção médica, com ênfase na doença, não existindo equipe multiprofissional para o atendimento às demandas psicológicas, sociais, etc. Além disso, constatou-se a falta de serviços de referência de reconstituição de mama, imprescindível no cuidado, quando se trata de garantia de atenção integral. Concluímos que é fundamental que a equipe gestora local repense a organização dos serviços e das práticas nos diversos níveis de complexidade do SUS de Volta Redonda, no atendimento às mulheres com câncer de mama e apoio a suas famílias, na perspectiva da integralidade e do direito à saúde. Por fim, o estudo defende o itinerário terapêutico como importante prática avaliativa em saúde, amistosa à integralidade, que pode ser incorporada ao cotidiano do SUS.

Synthesis of Silica Vesicles with Controlled Entrance Size for High Loading, Sustained Release, and Cellular Delivery of Therapeutical Proteins

A rationally designed two-step synthesis of silica vesicles is developed with the formation of vesicular structure in the first step and fine control over the entrance size by tuning the temperature in the second step. The silica vesicles have a uniform size of ≈50 nm with excellent cellular uptake performance. When the entrance size is equal to the wall thickness, silica vesicles after hydrophobic modification show the highest loading amount (563 mg/g) towards Ribonuclease A with a sustained release behavior. Consequently, the silica vesicles are excellent nano-carriers for cellular delivery applications of therapeutical biomolecules.

T-type calcium channel:from physiological function to therapeutical targeting – Exploring neuronal development

Tämän tutkimuksen tarkoitus oli tutkia T-tyypin kalsiumkanavan toimintaa ja sen mahdollista roolia neuronaalisten kantasolujen migraatiossa. T-tyypin kalsiumkanavan tehtävän kehittyneissä aivoissa tiedetään olevan elektroenkefalografisten oskillaatioiden tuottaminen. Nämä taas ovat eräiden fysiologisten ja patofysiologisten tapahtumien säätelyssä avainasemassa. Tällaisia tapahtumia ovat uni, muisti, oppiminen ja epileptiset poissaolokohtaukset. Näiden lisäksi T-tyypin kalsiumkanavalla on myös periferaalisia vaikutuksia, mutta tämä tutkielma keskittyy sen neuronaalisiin toimintoihin. Tämän matalan jännitteen säätelemän kanavan toiminta neurogeneesin aikana on vähemmän tutkittua ja tunnettua kuin sen vaikutukset kehittyneissä aivoissa. T-tyypin kalsiumkanavan tiedetään edistävän kantasolujen proliferaatiota ja erilaistumista neurogeneesiksen aikana, mutta vaikutukset niiden migraatioon ovat vähemmän tunnetut. Tämä tutkimus näyttää T-tyypin kalsiumkanavan todennäköisesti osallistuvan neuronaaliseen migraatioon hiiren alkion subventrikkeli alueelta eristetyillä kanta- tai progeniittorisoluilla tehdyissä kokeissa. Selektiiviset T-tyypin kalsiumkanavan antagonistit, etosuksimidi, nikkeli ja skorpionitoksiini, kurtoxin hidastivat migraatiota erilaistuvissa progeniittorisoluissa. Tämä tutkimus koostuu kirjallisuuskatsauksesta ja kokeellisesta osasta. Tämän tutkimuksen toinen tarkoitus oli esitellä vaihtoehtoinen lähestymistapa invasiiviselle kantasoluterapialle, joka vaatii kantasolujen viljelyä ja siirtämistä ihmiseen. Tämä toinen tapa on endogeenisten kantasolujen eiinvasiivinen stimulointi, jolla ne saadaan migratoitumaan kohdekudokseen, erilaistumaan siellä ja tehtävänsä suoritettuaan lopettamaan jakaantumisen. Non-invasiivinen kantasoluterapia on vasta tiensä alussa, ja tarvitsee farmakologista osaamista kehittyäkseen. Joitain onnistuneita ei-invasiivisia hoitoja on jo tehty selkärangan vaurioiden korjaamisessa. Vastaavanlaisia menetelmiä voitaisiin käyttää myös keskushermoston vaurioiden ja neurodegeneratiivisten sairauksien hoidossa. Näiden menetelmien kehittäminen vaatii endogeenisten kantasoluja inhiboivien ja indusoivien mekanismien tuntemista. Yksi tärkeä kantasolujen erilaistumista stimuloiva tekijä on kalsiumioni. Jänniteherkät kalsiumkanavat osallistuvat kaikkiin neurogeneesiksen eri vaiheisiin. T-tyypin kalsiumkanava, joka ekspressoituu suuressa määrin keskushermoston kehityksen alkuvaiheessa ja vähenee neuronaalisen kehityksen edetessä, saattaa olla oleellisessa asemassa progeniittorisolujen ohjaamisessa.

Water exchange rates of water-soluble manganese(III) porphyrins of therapeutical potential.

The activation parameters and the rate constants of the water-exchange reactions of Mn(III)TE-2-PyP(5+) (meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin) as cationic, Mn(III)TnHex-2-PyP(5+) (meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin) as sterically shielded cationic, and Mn(III)TSPP(3-) (meso-tetrakis(4-sulfonatophenyl)porphyrin) as anionic manganese(iii) porphyrins were determined from the temperature dependence of (17)O NMR relaxation rates. The rate constants at 298 K were obtained as 4.12 x 10(6) s(-1), 5.73 x 10(6) s(-1), and 2.74 x 10(7) s(-1), respectively. On the basis of the determined entropies of activation, an interchange-dissociative mechanism (I(d)) was proposed for the cationic complexes (DeltaS(double dagger) = approximately 0 J mol(-1) K(-1)) whereas a limiting dissociative mechanism (D) was proposed for Mn(III)TSPP(3-) complex (DeltaS(double dagger) = +79 J mol(-1) K(-1)). The obtained water exchange rate of Mn(III)TSPP(3-) corresponded well to the previously assumed value used by Koenig et al. (S. H. Koenig, R. D. Brown and M. Spiller, Magn. Reson. Med., 1987, 4, 52-260) to simulate the (1)H NMRD curves, therefore the measured value supports the theory developed for explaining the anomalous relaxivity of Mn(III)TSPP(3-) complex. A magnitude of the obtained water-exchange rate constants further confirms the suggested inner sphere electron transfer mechanism for the reactions of the two positively charged Mn(iii) porphyrins with the various biologically important oxygen and nitrogen reactive species. Due to the high biological and clinical relevance of the reactions that occur at the metal site of the studied Mn(iii) porphyrins, the determination of water exchange rates advanced our insight into their efficacy and mechanism of action, and in turn should impact their further development for both diagnostic (imaging) and therapeutic purposes.

Mucocele of the glands of Blandin-Nuhn-clinical, pathological, and therapeutical aspects

Purpose: This study aims to review anatomical, clinical, and pathological concepts as well as to discuss the most adequate therapeutic approach to the mucoceles of the glands of Blandin-Nuhn. Discussion: The glands of Blandin-Nuhn are localized in the ventral part of the tongue, next to the apex in the lingual median plane. Development of a mucocele in this site is rarely seen; besides, as the glands of Blandin-Nuhn are not encapsulated and are directly overlapped to the muscle tissues, their manipulation tends to be different from the other oral mucoceles. Conclusion: As Blandin-Nuhn mucoceles are uncommon and their clinical appearance could be similar to other lesions, it is important that health professionals know their clinical and histopathological features to avoid having them misdiagnosed. © 2010 Springer-Verlag.

Inhibition of inducible nitric oxide synthase-derived nitric oxide as a therapeutical target for acute pancreatitis induced by secretory phospholipase A(2)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Therapeutical potential of direct thrombin inhibitors for atherosclerotic vascular disease

Adverse cardiovascular events are the consequence of a molecular chain reaction at the site of vulnerable plaques. Key players are platelets and coagulation factors that are activated following plaque rupture and often cause arterial obstruction. Thrombin, a plasma serine protease, plays a role in hemostasis of coagulation as well as in thrombosis and cell growth, leading to restenosis and atherosclerosis. Interesting and promising new molecules, the direct thrombin inhibitors, have been shown to be as effective as the combination of glycoprotein IIb-IIIa inhibitors and heparin for the prevention of arterial thrombosis. Until recently, direct thrombin inhibitors could be applied only parenterally; therefore, therapy was limited to hospitalized patients. As a result of recent drug development, orally active direct thrombin inhibitors are now available and have been evaluated for the long-term treatment of venous thrombosis and arterial fibrillation. Due to their specific pharmacodynamic characteristics by binding directly to thrombin--and thus inhibiting platelet aggregation and fibrin generation--these novel drugs may also have therapeutic potential for the treatment of atherothrombotic disease and its complications such as myocardial infarction, stroke or limb ischemia.

Multimodal imaging in macular diagnostics: combined OCT-SLO improves therapeutical monitoring

BACKGROUND: Digital imaging methods are a centrepiece for diagnosis and management of macular disease. A recently developed imaging device is composed of simultaneous confocal scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT). By means of clinical samples the benefit of this technique concerning diagnostic and therapeutic follow-up will be assessed. METHODS: The combined OCT-SLO-System (Ophthalmic Technologies Inc., Toronto, Canada) allows for confocal en-face fundus imaging and high resolution OCT scanning at the same time. OCT images are obtained from transversal line scans. One light source and the identical scanning rate yield a pixel-to-pixel correspondence of images. Three-dimensional thickness maps are derived from C-scan stacking. RESULTS: We followed-up patients with cystoid macular edema, pigment epithelium detachment, macular hole, venous branch occlusion, and vitreoretinal tractions during their course of therapy. The new imaging method illustrates the reduction of cystoid volume, e.g. after intravitreal injections of either angiostatic drugs or steroids. C-scans are used for appreciation of lesion diameters, visualisation of pathologies involving the vitreoretinal interface, and quantification of retinal thickness change. CONCLUSION: The combined OCT-SLO system creates both topographic and tomographic images of the retina. New therapeutic options can be followed-up closely by observing changes in lesion thickness and cyst volumes. For clinical use further studies are needed.

Delay effects in the response of low-grade gliomas to radiotherapy: a mathematical model and its therapeutical implications

Low-grade gliomas (LGGs) are a group of primary brain tumours usually encountered in young patient populations. These tumours represent a difficult challenge because many patients survive a decade or more and may be at a higher risk for treatment-related complications. Specifically, radiation therapy is known to have a relevant effect on survival but in many cases it can be deferred to avoid side effects while maintaining its beneficial effect. However, a subset of LGGs manifests more aggressive clinical behaviour and requires earlier intervention. Moreover, the effectiveness of radiotherapy depends on the tumour characteristics. Recently Pallud et al. (2012. Neuro-Oncology, 14: , 1-10) studied patients with LGGs treated with radiation therapy as a first-line therapy and obtained the counterintuitive result that tumours with a fast response to the therapy had a worse prognosis than those responding late. In this paper, we construct a mathematical model describing the basic facts of glioma progression and response to radiotherapy. The model provides also an explanation to the observations of Pallud et al. Using the model, we propose radiation fractionation schemes that might be therapeutically useful by helping to evaluate tumour malignancy while at the same time reducing the toxicity associated to the treatment.

Targeting TRAF6 for Cancer Therapeutical Development

Tumor necrosis factor (TNF)-Receptor Associated Factors (TRAFs) are a family of signal transducer proteins. TRAF6 is a unique member of this family in that it is involved in not only the TNF superfamily, but the toll-like receptor (TLR)/IL-1R (TIR) superfamily. The formation of the complex consisting of Receptor Activator of Nuclear Factor κ B (RANK), with its ligand (RANKL) results in the recruitment of TRAF6, which activates NF-κB, JNK and MAP kinase pathways. TRAF6 is critical in signaling with leading to release of various growth factors in bone, and promotes osteoclastogenesis. TRAF6 has also been implicated as an oncogene in lung cancer and as a target in multiple myeloma. In the hopes of developing small molecule inhibitors of the TRAF6-RANK interaction, multiple steps were carried out. Computational prediction of hot spot residues on the protein-protein interaction of TRAF6 and RANK were examined. Three methods were used: Robetta, KFC2, and HotPoint, each of which uses a different methodology to determine if a residue is a hot spot. These hot spot predictions were considered the basis for resolving the binding site for in silico high-throughput screening using GOLD and the MyriaScreen database of drug/lead-like compounds. Computationally intensive molecular dynamics simulations highlighted the binding mechanism and TRAF6 structural changes upon hit binding. Compounds identified as hits were verified using a GST-pull down assay, comparing inhibition to a RANK decoy peptide. Since many drugs fail due to lack of efficacy and toxicity, predictive models for the evaluation of the LD50 and bioavailability of our TRAF6 hits, and these models can be used towards other drugs and small molecule therapeutics as well. Datasets of compounds and their corresponding bioavailability and LD50 values were curated based, and QSAR models were built using molecular descriptors of these compounds using the k-nearest neighbor (k-NN) method, and quality of these models were cross-validated.

Modern therapeutics, medical and surgical; including the diseases of women and children. A compendium of recent formulae and therapeutical directions from the practice of eminent contemporary physicians, American and foreign.

Combined ed. of his Modern medical therapeutics, Modern surgical therapeutics, Therapeutics of gynecology and Obstetrics, and Therapeutics of diseases of children.

Therapeutics, materia medica, and pharmacy, including the special therapeutics of diseases and symptoms, the physiological and therapeutical actions of drugs, the modern materia medica, official and practical pharmacy, minute directions for prescription writing, also the antidotal and antagonistic treatment of poisoning,

Tables on lining-papers.

A therapeutical arrangement of the materia medica, or, The materia medica arranged upon physiological principles ...

Mode of access: Internet.

Researches on phthisis. anatomical, pathological and therapeutical /

Translation of Recherches anatomiques, pathologiques et thérapeutiques sur la phthisie.

The pituitary : a study of the morphology, physiology, pathology, and surgical treatment of the pituitary, together with an account of the therapeutical uses of the extracts made from this organ /

Bibliographical foot-notes.