996 resultados para Ylä-Anttila, Pekka: Tieto


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We conducted a cross-sectional, hospital-based study between January 2006-March 2008 to estimate the resistance of Mycobacterium tuberculosis to first-line drugs in patients with tuberculosis at a Brazilian hospital. We evaluated the performance of the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] (MTT) microplate assay compared with the Bactec-MGIT 960 system for mycobacteria testing. The prevalence of resistance in M. tuberculosis was 6.7%. Multidrug-resistance [resistance to rifampicin (RMP) and isoniazid (INH)], INH-resistance and streptomycin (SM)-resistance accounted for 1%, 3.8% and 3.8% of all resistance, respectively, and all isolates were susceptible to ethambutol (EM). The resistance was primary in four cases and acquired in three cases and previous treatment was associated with resistance (p = 0.0129). Among the 119 M. tuberculosis isolates, complete concordance of the results for INH and EM was observed between the MTT microplate and Bactec-MGIT 960TM methods. The observed agreement for RMP was 99% (sensitivity: 90%) and 95.8% for SM (sensitivity 90.9%), lower than those for other drugs. The MTT colourimetric method is an accurate, simple and low-cost alternative in settings with limited resources.

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OBJECTIVE: The pharmacokinetic and pharmacodynamic properties of YM087, (4'-[(2-methyl-1,4,5,6- tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)-carbonyl]-2-p henylbenzanilide monohydrochloride), a new orally active, dual V1/V2 receptor antagonist were characterised in healthy normotensive subjects. METHODS: Six subjects were randomly allocated to receive, at 1-week intervals, a single oral dose of 60 mg YM087 and a single i.v. dose of 50 mg YM087 in an open-label, crossover study. RESULTS: YM087 had an oral bioavailability of 44% and a short half-life. Upon oral and i.v. administration of YM087, a significant sevenfold increase in urine flow rate and a fall in urinary osmolality (from 600 mosmol/l to less than 100-mosmol/l) were observed with a peak effect 2 h after drug intake suggesting effective vasopressin V2 receptor blockade. Simultaneously, significant increases in plasma osmolality (from 283 +/- 1.3 mosmol/l to 288 +/- 1.0 mosmol/l after i.v. and from 283 +/- 2.1 mosmol/l to 289 +/- 1.7-mosmol/l after oral administration) and vasopressin levels (from 1.5 +/- 0.3 pg/ml to 3.7 +/- 0.6 pg/ml after i.v. and from 0.9 +/- 0.1 pg/ml to 3.9 +/- 0.7 pg/ml after oral administration) were found. When administered i.v., YM087 inhibited the vasopressin-induced skin vasoconstriction, suggesting a blockade of V1 receptors. However, the YM087-induced antagonism of V1 receptors was less pronounced than V2 receptor blockade. CONCLUSION: These data show that YM087 is an effective dual V1/V2 receptor antagonist in man.

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PURPOSE: Estradiol (E2) modulates testicular functions including steroidogenesis, but the mechanisms of E2 signaling in human testis are poorly understood. GPER-1 (GPR30), a G protein-coupled membrane receptor, mediates rapid genomic and non-genomic response to estrogens. The aim of this study was to evaluate GPER-1 expression in the testis, and its role in estradiol dependent regulation of steroidogenesis in isolated rat Leydig cells and human testis. MATERIALS AND METHODS: Isolated Leydig cells (LC) from adult rats and human testicular tissue were used in this study. Expression and localization studies of GPER-1 were performed with qRT-PCR, immunofluorescence, immunohistochemistry and Western Blot. Luteinizing Hormone (LH) -stimulated, isolated LC were incubated with estradiol, G-1 (GPER-1-selective agonist), and estrogen receptor antagonist ICI 182,780. Testosterone production was measured with radioimmunoassay. LC viability after incubation with G-1 was measured using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. RESULTS: GPER-1 mRNA is abundantly expressed in rat LC and human testis. Co-localization experiments showed high expression levels of GPER-1 protein in LC. E2-dependent activation of GPER-1 lowers testosterone production in isolated rats LCs and in human testis, with statistically and clinically significant drops in testosterone production by 20-30% as compared to estradiol-nave LC. The exposure to G-1 does not affect viability of isolated LCs. CONCLUSIONS: Our results indicate that activation of GPER-1 lowers testosterone levels in the rat and human testis. The expression of GPER-1 in human testis, which lack ERα, makes it an exciting target for developing new agents affecting testosterone production in men.

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We evaluated the in vitro anti-Mycobacterium tuberculosis activity and the cytotoxicity of dichloromethane extract and pure compounds from the leaves of Calophyllum brasiliense. Purification of the dichloromethane extract yielded the pure compounds (-) mammea A/BB (1), (-) mammea B/BB (2) and amentoflavone (3). The compound structures were elucidated on the basis of spectroscopic and spectrometric data. The contents of bioactive compounds in the extracts were quantified using high performance liquid chromatography coupled to an ultraviolet detector. The anti-M. tuberculosis activity of the extracts and the pure compounds was evaluated using a resazurin microtitre assay plate. The cytotoxicity assay was performed in J774G.8 macrophages using the 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide colourimetric method. The quantification of the dichloromethane extract showed (1) and (2) at concentrations of 31.86 ± 2.6 and 8.24 ± 1.1 µg/mg of extract, respectively. The dichloromethane and aqueous extracts showed anti-M. tuberculosis H37Rv activity of 62.5 and 125 µg/mL, respectively. Coumarins (1) and (2) showed minimal inhibitory concentration ranges of 31.2 and 62.5 µg/mL against M. tuberculosis H37Rv and clinical isolates. Compound (3) showed no activity against M. tuberculosis H37Rv. The selectivity index ranged from 0.59-1.06. We report the activity of the extracts and coumarins from the leaves of C. brasiliense against M. tuberculosis.

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In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation.

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PURPOSE: This study investigates the effects of triamcinolone acetonide (TA) on retinal endothelial cells in vitro and explores the potential vascular toxic effect of TA injected into the vitreous cavity of rats in vivo. METHODS: Subconfluent endothelial cells were treated with either 0.1 mg/ml or 1 mg/ml TA in 1% ethanol. Control cells were either untreated or exposed to 1% ethanol. Cell viability was evaluated at 24 h, 72 h, and five days using the tetrazolium 3-(4,5-dimethylthiazol-2-yl)-2,5 phenyltetrazolium bromide test (MTT) and lactate dehydrogenase (LDH) assays. Cell proliferation was evaluated by 5-bromo-2-deoxyuridine (BrdU) test. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL assay), annexin-binding, and caspase 3 activation. Caspase-independent cell deaths were investigated by immunohistochemistry using antibodies against apoptosis inducing factor (AIF), cytochrome C, microtubule-associated protein (MAP)-light chain 3 (MAP-LC3), and Leukocyte Elastase Inhibitor/Leukocyte Elastase Inhibitor-derived DNase II (LEI/L-DNase II). In vivo, semithin and ultrathin structure analysis and vascular casts were performed to examine TA-induced changes of the choroidal vasculature. In addition, outer segments phagocytosis assay on primary retinal pigment epithelium (RPE) cells was performed to assess cyclooxygenase (COX-2) and vascular endothelial growth factor (VEGF) mRNAs upregulation with or without TA. RESULTS: The inhibitory effect of TA on cell proliferation could not explain the significant reduction in cell viability. Indeed, TA induced a time-dependent reduction of bovine retinal endothelial cells viability. Annexin-binding positive cells were observed. Cytochrome C was not released from mitochondria. L-DNase II was found translocated to the nucleus, meaning that LEI was changed into L-DNase II. AIF was found nuclearized in some cells. LC3 labeling showed the absence of autophagic vesicles. No autophagy or caspase dependent apoptosis was identified. At 1 mg/ml TA induced necrosis while exposure to lower concentrations for 3 to 5 days induced caspase independent apoptosis involving AIF and LEI/L-DNase II. In vivo, semithin and ultrathin structure analysis and vascular casts revealed that TA mostly affected the choroidal vasculature with a reduction of choroidal thickness and increased the avascular areas of the choriocapillaries. Experiments performed on primary RPE cells showed that TA downregulates the basal expression of COX-2 and VEGF and inhibits the outer segments (OS)-dependent COX-2 induction but not the OS-dependent VEGF induction. CONCLUSIONS: This study demonstrates for the first time that glucocorticoids exert direct toxic effect on endothelial cells through caspase-independent cell death mechanisms. The choroidal changes observed after TA intravitreous injection may have important implications regarding the safety profile of TA use in human eyes.

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New derivatives of 1,4-dideoxy-1,4-imino-D-ribitol have been prepared and evaluated for their cytotoxicity on solid and haematological malignancies. 1,4-Dideoxy-5-O-[(9Z)-octadec-9-en-1-yl]-1,4-imino-D-ribitol (13, IC(50) &#8764;2 &#956;M) and its C(18)-analogues (IC(50) <10 &#956;M) are cytotoxic toward SKBR3 (breast cancer) cells. 13 also inhibits (IC(50) &#8764;8 &#956;M) growth of JURKAT cells.

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Inner ear hair cells and supporting cells arise from common precursors and, in mammals, do not show phenotypic conversion. Here, we studied the role of the homeodomain transcription factor Prox1 in the inner ear sensory epithelia. Adenoviral-mediated Prox1 transduction into hair cells in explant cultures led to strong repression of Atoh1 and Gfi1, two transcription factors critical for hair cell differentiation and survival. Luciferase assays showed that Prox1 can repress transcriptional activity of Gfi1 independently of Atoh1. Prox1 transduction into cochlear outer hair cells resulted in degeneration of these cells, consistent with the known phenotype of Gfi1-deficient mice. These results together with the widespread expression of endogenous Prox1 within the population of inner ear supporting cells point to the role for Prox1 in antagonizing the hair cell phenotype in these non-sensory cells. Further, in vivo analyses of hair cells from Gfi1-deficient mice suggest that the cyclin-dependent kinase inhibitor p57(Kip2) mediates the differentiation- and survival-promoting functions of Gfi1. These data reveal novel gene interactions and show that these interactions regulate cellular differentiation within the inner ear sensory epithelia. The data point to the tight regulation of phenotypic characteristics of hair cells and supporting cells.

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BACKGROUND: Ductal carcinoma in situ (DCIS) incidence has grown with the implementation of screening and its detection varies across International Cancer Screening Network (ICSN) countries. The aim of this survey is to describe the management of screen-detected DCIS in ICSN countries and to evaluate the potential for treatment related morbidity. METHODS: We sought screen-detected DCIS data from the ICSN countries identified during 2004-2008. We adopted standardised data collection forms and analysis and explored DCIS diagnosis and treatment processes ranging from pre-operative diagnosis to type of surgery and radiotherapy. RESULTS: Twelve countries contributed data from a total of 15 screening programmes, all from Europe except the United States of America and Japan. Among women aged 50-69years, 7,176,050 screening tests and 5324 screen-detected DCIS were reported. From 21% to 93% of DCIS had a pre-operative diagnosis (PO); 67-90% of DCIS received breast conservation surgery (BCS), and in 41-100% of the cases this was followed by radiotherapy; 6.4-59% received sentinel lymph node biopsy (SLNB) only and 0.8-49% axillary dissection (ALND) with 0.6% (range by programmes 0-8.1%) being node positive. Among BCS patients 35% received SLNB only and 4.8% received ALND. Starting in 2006, PO and SLNB use increased while ALND remained stable. SLNB and ALND were associated with larger size and higher grade DCIS lesions. CONCLUSIONS: Variation in DCIS management among screened women is wide and includes lymph node surgery beyond what is currently recommended. This indicates the presence of varying levels of overtreatment and the potential for its reduction.

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Tss insinrityss selvitettiin mahdollisuuksia parantaa Tapiola-ryhmn Yhtikokousjrjestelm-ohjelmiston ominaisuuksia ja tietoturvallisuutta. Jrjestelm kytetn Tapiola-ryhmn vakuutusyhtiiden yhtikokouksiin osallistuvien osakkaiden kirjaamiseen ja heidn nten laskentaan. Tutkimuksen perusteella tehtiin jrjestelmn mrittely ja suunnittelu, joiden tuloksena syntyivt toiminnallinen ja tekninen mrittelydokumentaatio, jotka toimivat pohjana uuden Yhtikokousjrjestelmn toteutukselle. Ty tehtiin Tapiola-ryhmlle Tieto-Tapiola Oy:n tilauksesta. Tyn alussa tutkittiin erilaisia mahdollisuuksia toteuttaa jrjestelmn ohjelmisto- ja tietokanta-arkkitehtuuri, joiden perusteella mrittely ja suunnittelua alettiin toteuttaa. Tutkimuksen perusteella pdyttiin kyttmn Java SE -arkkitehtuuria sovelluksen toteutukseen ja SQL Server -tietokantaa jrjestelmn tietovarastona. Valittuihin ratkaisuihin pdyttiin niiden hyvien tietoturvallisuus- ja kertakirjausominaisuuksien takia. Toiminnallisessa mrittelydokumentissa kydn lpi jrjestelmlle asetettuja vaatimuksia ja kuvataan sen toiminnot, liiketoimintaluokkamalli, kyttliittym ja tulosteet. Lisksi siin otetaan kantaa jrjestelmn kyttympristn, ulkoisiin tietokantaliittymiin, kyttjn tunnistautumiseen ja tietoturvallisuuteen sek kydn lpi sen toiminta kyttjien nkkulmasta. Toiminnallisen mrittelydokumentin pohjalta luotiin tekninen mrittelydokumentti. Siin kuvataan jrjestelmn ymprist ja ohjelmisto- sek tietokanta-arkkitehtuuri yleisell tasolla. Tmn lisksi jrjestelmn arkkitehtuuria kydn mys tarkemmin lpi sek kuvataan moduulit ja toiminnot niin tarkasti, ett niiden perusteella voidaan toteuttaa koko jrjestelm. Tyn tuloksena syntyivt kattava toiminnallinen ja tekninen mrittelydokumentaatio, joissa kydn lpi kaikki jrjestelmn toteuttamiseen tarvittavat elementit sill tarkkuudella, ett jrjestelmn toteuttaminen voidaan aloittaa.

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Tss insinrityss tehtiin layout-suunnitelmat C-huoltotelakoista Airbus 340 -lentokoneiden huoltoa varten ja selvitettiin samojen huoltotelakoiden kyttmahdollisuutta mys muiden konetyyppien huolloissa. Insinrityn toimeksiantajana toimi Finnairin tekniikan lentokonekorjaamo, jonka kyttn huoltotelakat suunniteltiin. Ty aloitettiin perehtymll Airbus 340 -lentokoneen mittoihin ja C-huoltotarpeisiin. Seuraavaksi kytiin lpi erilaisia huoltotelakkavaihtoehtoja ja niiden aiheuttamia kustannuksia pitkll ajanjaksolla. Huoltotelakoiden soveltuvuutta tarkasteltiin eri lentokonetyypien kyttn. Huoltotelakoiden suunnittelussa huomioitiin mys niiden varastointivaatimukset. Lisksi tyss kytiin lpi viranomaisten turvallisuusvaatimukset sek lentokonehuoltotoiminnan erityisvaatimukset huoltotelakoille. Tyn tuloksena syntyneit investointilaskelmia ja layout-suunnitelmia kytetn hydyksi valittaessa kustannuksiltaan ja kyttvaatimuksiltaan parhaiten Airbus 340 -lentokoneiden C-huoltovaatimuksia vastaava huoltotelakkavaihtoehto. Huoltotelakoiden layout-suunnitelmat on tehty tyntekijiden nkkulmat huomioiden, jotta tynteko olisi tehokasta ja ergonomista.

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Opinnytteemme aiheena on kirjoittamisen kehittyminen, vaikeudet ja tukikeinot 1. ja 2. luokan oppilailla. Tyelmn yhteistykumppanit opinnytetyssmme olivat Tikkurilan terveysaseman toimintaterapeutit. Opinnytetymme tarkoitus oli tehd yhteistykumppaneiden kyttn kirjallista materiaalia konsultaation tueksi kirjoittamisen vaikeuksista krsivien lasten koulutyskentelyyn. Ty on rajattu ksittelemn kirjoittamista kden taitona. Rajauksesta johtuen ksittelemme tyssmme kirjoittamista posin ksialan tuottamisen nkkulmasta, mutta emme perehdy kirjoitetun tekstin sislln tuottamiseen. Toimintaterapeuttien tarkoituksena on luovuttaa tyst heidn mielestn tarpeellinen tieto eteenpin opettajille oppilaan kirjoittamisen arvioinnin jlkeen. Opinnytetymme muoto on teoreettinen, kirjallisuuskatsauksen tyyppinen ty. Tymme lhtein kytimme posin toimintaterapia-alan lasten kirjoittamista ksittelev kirjallisuutta ja tieteellisi tutkimusartikkeleita. Lysimme opinnytetytmme tehdessmme runsaasti kirjoittamisen tukemisen keinoja toimintaterapian nkkulmasta. Kirjoittamisen tukemista koululuokassa ksittelimme lapsen koulunkynnist selviytymisen nkkulmasta coping-viitekehyst hydynten. Ennen kirjoittamisen tukemiseen liittyvien keinojen selvittmist tyss oli tarpeellista selvitt kirjoittamisen kannalta olennaisia asioita. Nit olivat kirjoittamisen kehittyminen kden taitona, kirjoittamiseen vaadittavat taidot ja valmiudet, kouluympristn vaatimukset kirjoittamiselle, sek kirjoittamisessa ilmenevt vaikeudet ja niiden vaikutukset oppilaan toimintaan. Kirjoittaminen on vaativa ja monimutkainen taito. Se on arvokas, koulunkynti ja oppimista mahdollistava vlinetaito. Vaikeudet kirjoittamisessa voivat johtua useista eri syist, joten yht oikeaa keinoa tai menetelm kirjoittamisen tukemiseen ei ole. Kirjoittamista koululuokassa voidaan pyrki tukemaan toimintataterapian nkkulmasta vaikuttamalla oppilaan sisisiin voimavaroihin, ja/tai kouluympristn voimavaroihin. Oppilaan suoriutumista kirjoittamisesta voidaan tukea mys toiminnan vaatimuksia muuttamalla. Toivoisimme, ett tulevilta opinnytteen tekijilt lytyisi kiinnostusta jatkaa tytmme. Ehdotuksiamme jatkotyn aiheiksi ovat Opas kirjoittamisen tukemiseksi opettajille, tai Opas kirjoittamisen tukemiseksi toimintaterapeuteille.

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Tmn toiminnallisen opinnytetyn tarkoitus oli toteuttaa suun terveyden edistmisnytelm. HUS:n Kipin ja Kunttari kuntoutumisosastoille, joiden asukkaat ovat 14-18-vuotiaita mielenterveyskuntoutujia. Opinnytetyn tavoitteena oli list nuorten suun terveydenlukutaitoa. Nytelmn tavoitteena oli innostaa nuoria suun terveydenhoitoon. Terveydenedistmismenetelmn kytettiin draamaa. Lukuisat tutkimukset viittaavat siihen, ett nuorten elintavat ovat muuttuneet epterveellisempn suuntaan. Alueelliset terveyserot heijastuvat mys suunterveyteen. Helsingiss on moniongelmaisia perheit, nuoria ja lapsia suhteellisesti enemmn kuin muualla Suomessa. Opinnytetyss sovellettiin Precede-Proceed -terveyden edistmismallia, joka nkyy tymme suunnittelu-, toteutus- ja arviointivaiheessa. Suun terveydenedistmisnytelm Liian hapokasta suunniteltiin ja toteutettiin opinnytetyryhmss yhteistyss tyelmyhteistykumppanin kanssa. Nytelm oli luonteeltaan osallistava. Tm tarkoittaa sit, ett yleis sai itse vaikuttaa nytelmn kulkuun valitsemalla kahdesta eri vaihtoehdosta sopivimman. Nytelmn keskeiset aihealueet valittiin nyttn ja kokemukseen perustuen ja ne olivat: suun hoito, tupakointi, iensairaudet, karies ja ravitsemus. Tlle tylle sovellus- ja jatkomahdollisuudet voisivat olla tutkia millaisen terveyden lukutaidon nuoret saavuttivat. Tymme voi toimia mys esimerkkin tulevien terveyden edistmisnytelmien toteutuksille ja ksikirjoituksille.

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The aim of this thesis is to present a solution to the quantum phase problem of the single-mode optical field. The solution is based on the use of phase shift covariant normalized positive operator measures. These measures describe realistic direct coherent state phase measurements such as the phase measurement schemes based on eight-port homodyne detection or heterodyne detection. The structure of covariant operator measures and, more generally, covariant sesquilinear form measures is analyzed in this work. Four different characterizations for phase shift covariant normalized positive operator measures are presented. The canonical covariant operator measure is definded and its properties are studied. Finally, some other suggested phase theories are introduced to investigate their connections to the covariant sesquilinear form measures.