Modulation of cytochrome P450 monooxygenase by cadmium chloride in the mouse liver: Involvement of transcription factor Nrf2.

Modulation of the cytochrome P450 (CYP) monooxygenase system and haem oxygenase by cadmium was investigated in male, adult DBA/2J mice treated with a single dose (16 Amol/kg body weight, i.p.) of cadmium chloride (CdCl2), at various time points. Total CYP content of liver microsomes decreased significantly (P < 0.05) at 12, 18, and 24 hours (22%, 47%, and 56%, respectively) after treatment. In contrast, progressive increases of hepatic coumarin 7-hydroxylase (COH) activity (indicative of CYP2A5 activity) were observed at 8 hrs (2-fold), 12 hrs (3-fold), and 7-fold at 18 and 24 hrs. Simultaneously, haem oxygenase activity increased significantly at 4 hours and continued to increase progressively to more than 50-fold compared to control. Liver CYP2A5 mRNA levels increased maximally 12 hours after treatment and decreased to almost half 6 hours later, while western blot analysis showed 2- and 3- fold increase in CYP2A5 apoprotein at 12 and 24 hours. The CYP2A5 mRNA levels in the liver increased after Cd treatment in Nrf2 +/+ but not in Nrf2 / mouse. This study demonstrates that hepatic haem oxygenase and CYP2A5 are upregulated by cadmium. The upregulation of haem oxygenase precedes that of CYP2A5. The strong upregulation of the CYP2A5 both at mRNA and enzyme activity levels, with a simultaneous decrease in the total CYP concentration suggest an unusual mode of regulation of CYP2A5 in response to cadmium exposure, amongst the CYP enzymes. The observed increase in the mRNA but not in protein levels after maximal induction may suggest involvement of post-transcriptional mechanisms in the regulation. Upregulation of CYP2A5 by cadmium in the Nrf2 +/+ mice but not in the Nrf2 / mice indicates a role for this transcription factor in the regulation.

Complexes of copper(II) with 3-(ortho-substituted phenylhydrazo)pentane-2,4-diones: syntheses,properties and catalytic activity for cyclohexane oxidation

Reactions of copper(II) with 3-phenylhydrazopentane-2,4-diones X-2-C6H4-NHN = C{C(= O)CH3}(2) bearing a substituent in the ortho-position [X = OH (H2L1) 1, AsO3H2 (H3L2) 2, Cl (HL3) 3, SO3H (H2L4) 4, COOCH3 (HL5) 5, COOH (H2L6) 6, NO2 (HL7) 7 or H (HL8) 8] lead to a variety of complexes including the monomeric [CuL4(H2O)(2)]center dot H2O 10, [CuL4(H2O)(2)] 11 and [Cu(HL4)(2)(H2O)(4)] 12, the dimeric [Cu-2(H2O)(2)(mu-HL2)(2)] 9 and the polymeric [Cu(mu-L-6)](n)] 13 ones, often bearing two fused six-membered metallacycles. Complexes 10-12 can interconvert, depending on pH and temperature, whereas the Cu(II) reactions with 4 in the presence of cyanoguanidine or imidazole (im) afford the monomeric compound [Cu(H2O)(4){NCNC(NH2)(2)}(2)](HL4)(2)center dot 6H(2)O 14 and the heteroligand polymer [Cu(mu-L-4)(im)](n) 15, respectively. The compounds were characterized by single crystal X-ray diffraction (complexes), electrochemical and thermogravimetric studies, as well as elemental analysis, IR, H-1 and C-13 NMR spectroscopies (diones) and ESI-MS. The effects of the substituents in 1-8 on the HOMO-LUMO gap and the relative stability of the model compounds [Cu(OH)(L-8)(H2O)]center dot H2O, [Cu(L-1)(H2O)(2)]center dot H2O and [Cu(L-4)(H2O)(2)]center dot H2O are discussed on the basis of DFT calculations that show the stabilization follows the order: two fused 6-membered > two fused 6-membered/5-membered > one 6-membered metallacycles. Complexes 9, 10, 12 and 13 act as catalyst precursors for the peroxidative oxidation (with H2O2) of cyclohexane to cyclohexanol and cyclohexanone, in MeCN/H2O (total yields of ca. 20% with TONs up to 566), under mild conditions.

A causa dos divertimentos

Texto justificativo para a atribuição da Menção Especial da Crítica 2011 ao actor Miguel Guilherme pela sua interpretação em O senhor Puntilla e o seu criado Matti, de Bertolt Brecht (enc. João Lourenço / Teatro Aberto, 2010).

Adipose-derived stem cells enhance peripheral nerve regeneration.

Traumatic injuries resulting in peripheral nerve lesions often require a graft to bridge the gap. Although autologous nerve auto-graft is still the first-choice strategy in reconstructions, it has the severe disadvantage of the sacrifice of a functional nerve. Cell transplantation in a bioartificial conduit is an alternative strategy to create a favourable environment for nerve regeneration. We decided to test new fibrin nerve conduits seeded with various cell types (primary Schwann cells and adult stem cells differentiated to a Schwann cell-like phenotype) for repair of sciatic nerve injury. Two weeks after implantation, the conduits were removed and examined by immunohistochemistry for axonal regeneration (evaluated by PGP 9.5 expression) and Schwann cell presence (detected by S100 expression). The results show a significant increase in axonal regeneration in the group of fibrin seeded with Schwann cells compared with the empty fibrin conduit. Differentiated adipose-derived stem cells also enhanced regeneration distance in a similar manner to differentiated bone marrow mesenchymal stem cells. These observations suggest that adipose-derived stem cells may provide an effective cell population, without the limitations of the donor-site morbidity associated with isolation of Schwann cells, and could be a clinically translatable route towards new methods to enhance peripheral nerve repair.

Muscle recovery after repair of short and long peripheral nerve gaps using fibrin conduits.

Peripheral nerve injuries with loss of nervous tissue are a significant clinical problem and are currently treated using autologous nerve transplants. To avoid the need for donor nerve, which results in additional morbidity such as loss of sensation and scarring, alternative bridging methods have been sought. Recently we showed that an artificial nerve conduit moulded from fibrin glue is biocompatible to nerve regeneration. In this present study, we have used the fibrin conduit or a nerve graft to bridge either a 10 mm or 20 mm sciatic nerve gap and analyzed the muscle recovery in adult rats after 16 weeks. The gastrocnemius muscle weights of the operated side were similar for both gap sizes when treated with nerve graft. In contrast, muscle weight was 48.32 ± 4.96% of the contra-lateral side for the 10 mm gap repaired with fibrin conduit but only 25.20 ± 2.50% for the 20 mm gap repaired with fibrin conduit. The morphology of the muscles in the nerve graft groups showed an intact, ordered structure, with the muscle fibers grouped in fascicles whereas the 20 mm nerve gap fibrin group had a more chaotic appearance. The mean area and diameter of fast type fibers in the 20 mm gap repaired with fibrin conduits were significantly (P<0.01) worse than those of the corresponding 10 mm gap group. In contrast, both gap sizes treated with nerve graft showed similar fiber size. Furthermore, the 10 mm gaps repaired with either nerve graft or fibrin conduit showed similar muscle fiber size. These results indicate that the fibrin conduit can effectively treat short nerve gaps but further modification such as the inclusion of regenerative cells may be required to attain the outcomes of nerve graft for long gaps.

Circulating estrogens and progesterone during primiparous pregnancies and risk of maternal breast cancer.

Pregnancy reduces maternal risk of breast cancer in the long term, but the biological determinants of the protection are unknown. Animal experiments suggest that estrogens and progesterone could be involved, but direct human evidence is scant. A case-control study (536 cases and 1,049 controls) was nested within the Finnish Maternity Cohort. Eligible were primiparous women who delivered at term a singleton offspring before age 40. For each case, two individually matched controls by age (±6 months) and date of sampling (±3 months) were selected. Estradiol, estrone and progesterone in first-trimester serum were measured by high-performance liquid chromatography tandem mass spectrometry and sex-hormone binding globulin (SHBG) by immunoassay. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through conditional logistic regression. In the whole study population there was no association of breast cancer with any of the studied hormones. In analyses stratified by age at diagnosis, however, estradiol concentrations were positively associated with risk of breast cancer before age 40 (upper quartile OR, 1.81; CI, 1.08-3.06), but inversely associated with risk in women who were diagnosed ≥age 40 (upper quartile OR, 0.64; CI, 0.40-1.04), p(interaction) 0.004. Risk estimates for estrone mirrored those for estradiol but were less pronounced. Progesterone was not associated with risk of subsequent breast cancer. Our results provide initial evidence that concentrations of estrogens during the early parts of a primiparous pregnancy are associated with maternal risk of breast cancer and suggest that the effect may differ for tumors diagnosed before and after age 40.

Insulin-like growth factor-I and C-reactive protein during pregnancy and maternal risk of non-epithelial ovarian cancer: a nested case-control study.

BACKGROUND: Insulin-like growth factor-I (IGF-I) and C-reactive protein (CRP) may be positively associated with the risk of epithelial ovarian cancer (EOC) but no previous studies have investigated their associations with non-epithelial ovarian cancers (NEOC). METHODS: A case-control study was nested within the Finnish Maternity Cohort. Case subjects were 58 women diagnosed with sex cord-stromal tumors (SCST) and 30 with germ cell tumors (GCT) after recruitment. Control subjects (144 for SCST and 74 for GCT) were matched for age, parity, and date of blood donation of the index case. RESULTS: Doubling of IGF-I concentration was not related to maternal risk of either SCST (OR 0.97, 95% CI 0.58-1.62) or GCT (OR 1.13, 95% CI 0.51-2.51). Similarly, doubling of CRP concentrations was not related to maternal risk of either SCST (OR 1.10, 95% CI 0.85-1.43) or GCT (OR 0.93, 95% CI 0.68-1.28). CONCLUSIONS: Pre-diagnostic IGF-I and CRP concentrations during the first trimester of pregnancy were not associated with increased risk of NEOC in the mother. Risk factors for NEOC may differ from those of EOC.

Circulating insulin-like growth factor-I in pregnancy and maternal risk of breast cancer.

BACKGROUND: Elevated serum concentrations of insulin-like growth factor (IGF)-1 have been associated with increased risk of breast cancer. Previously, we reported a similar association in samples obtained during pregnancy. The current study was conducted to further characterize the association of IGF-1 during pregnancy with maternal breast cancer risk. METHODS: A case-control study was nested within the Finnish Maternity Cohort. The study was limited to primiparous women less than 40 years of age, who donated blood samples during early (median, 12 weeks) pregnancy and delivered a single child at term. Seven hundred and nineteen women with invasive breast cancer were eligible. Two controls (n = 1,434) were matched to each case on age and date at blood donation. Serum IGF-1 concentration was measured using an Immulite 2000 analyzer. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI).RESULTS: No significant associations were observed between serum IGF-1 concentrations and breast cancer risk in both the overall analysis (OR 1.08 (95% CI 0.80-1.47) and in analyses stratified by histological subtype, lag-time to cancer diagnosis, age at pregnancy or age at diagnosis.CONCLUSIONS: There was no association between IGF-1 and maternal breast cancer risk during early pregnancy in this large nested case-control study.Impact:Serum IGF-1 concentrations during early pregnancy may not be related to maternal risk of breast cancer.

Sensate lateral arm flap for defects of the lower leg.

Ideally, reconstruction of lower extremity soft tissue defects includes not only an esthetically pleasing 3-dimensional shape and solid anchoring to the underlying structures to resist shear forces, but should also address the restoration of sensation. Therefore, we present a prospective study on defect reconstruction of the lower leg and ankle to evaluate the role of sensate free fasciocutaneous lateral arm flap and the impact of sensory nerve reconstruction. Thirty patients were allocated randomly to the study group (n = 15) that obtained end-to-side sensate coaptation using the lower lateral cutaneous brachial nerve to the tibial nerve using the epineural window technique, or to the control group reconstructed without nerve coaptation. At 1-year follow-up the patients were evaluated for pain sensation, thermal sensibility, static and moving 2-point discrimination, and Semmes-Weinstein monofilament tests. Data from both groups were compared and statistically analyzed with the Mann-Whitney U test and the Fisher exact test. Flaps of the study group reached a static and moving 2-point discrimination and Semmes-Weinstein monofilament tests nearly equal to the contralateral leg area and significantly better than flaps of the control group. Donor damage morbidity of the tibial nerve did not occur. To our point of view resensation should be carried out by end-to-side neurorrhaphy to the tibial nerve because of the superior restoration of sensibility.

Isä pienen lapsen hoitajana : katsaus isyyteen ja perusasioita isän toimimisesta pienen lapsen hoitajana

Opinnäytetyöni kuuluu Helsingin ammattikorkeakoulun ja Tampereen yliopiston yhteiseen projektiin nimeltään 'Urbaani vanhemmuus', jonka tarkoituksena on tukea vauvaperheiden hyvinvointia loppuraskauden ja vauvan ensimmäisen elinvuoden aikana. Oma työni kuvaa isyyden kehitystä ja muutosta sekä kuvaa isän toimimista pienen lapsen hoitajana sekä siinä huomioitavia seikkoja pääpiirteissään. Opinnäytetyöni on toiminnallinen opinnäytetyö, jossa tämän työn ohella toinen lopputuote on verkkosivut pienen lapsen vanhemmille, jossa oma osioni on kohdistettu isille. 1950-luvun jälkeen isyyden roolimalli ja isyys itsessään on elänyt varsin voimakasta muutoksen ja muutostarpeen aikaa. Vanhakantaisesta patriarkaalisesta isyydestä on luovuttu tai siitä ollaan luopumassa. Sen tilalle on nousemassa uusia isyyden roolimalleja tai pikemminkin miesnäkökulmia, kuten "uusi isyys", joka on noussut varsinaisesti esille Suomessa 1990-luvulla. Sen keskeisenä ajatuksena on isien samanarvoinen sitoutuminen lapsenhoitoon, kotitöihin ja parisuhteeseen kuin aikaisemmin on totuttu näkemään naisen/äidin rooliin kuuluvana. Myös naisten korkeampi kouluttautuminen ja aikaisempaa suurempi osuus työelämässä sekä kasvaneet vaatimukset perhe-elämän ja työnteon suhteen ovat olleet voimakkaasti vaikuttamassa tarpeeseen isien roolin uudelleenmäärittelemiseksi. Merkittävää osuutta myös nykyisessä sukupuoliroolien uudelleenjakautumisessa on näytellyt lisääntyvä individualismi. Se vaikuttaa toisaalta naisten/äitien kautta niin etteivät he halua enää "alistua kodinhengettäriksi" ja lapsen kasvattajiksi, vaan he haluavat toteuttaa enemmän itseään ja omia päämääriään sekä työelämässä että vapaa-ajallaan. Toisaalta isät voivat sen taustavaikuttamana pyrkiä entistä vahvemmin toimimaan omien altruitististen motiiviensa mukaan sekä pyrkiä "toteuttamaan itseään" joko perheen ulkopuolella tai omien tarkoitusperiensä mukaisesti perheessä vanhan patriarkaalisen roolimallin mukaisesti. Isyyttä ei nykyään nähdä samanlaisena ja automaattisena asiana kuin se on totuttu näkemään aikaisemmin. Avioerojen ja uusperheiden sekä yksinhuoltajuuden ja lasten sijoittamisen lisääntyvät määrät ovat muokanneet isyyttä ja antaneet sille uusia mahdollisuuksia biologisen, juridisen, sosiaalisen ja psykologisen isyyden muodoissa sekä niiden toteuttamisen/toteutumisen suhteen. Myös nykyaikaiset perhe- ja kumppanuusmuodot ovat nostaneet perinteisen käsitteen ydinperheen tarpeellisuudesta ja välttämättömyydestä lapselle esille ja tarkasteltavaksi. Myös isä voi niin halutessaan oppia toimimaan hyvänä hoitajana lapselleen. Perushoidolliset asiat ovat hyvinkin yksinkertaisia koskien lapsen fyysistä hoitamista ja henkistä läsnäoloa. Myös vanhempien omaan jaksamiseen tulisi kiinnittää huomiota, jotta tilanne ei muodostuisi kohtuuttomaksi kenellekään..

Sähköpyörätuolin jalkaohjauslaite

Opinnäytetyömme käsitti tuotekehitysprojektin, jossa suunnittelimme, kehitimme ja valmistimme jalkaohjauslaitteen sähköpyörätuoliin. Idea tuotekehitysprojektiin tuli Pasi Mäkirannalta. Tuotekehitysprojektin ideana oli kehittää parempi ja käytännöllisempi jalkaohjauslaite. Jalkaohjauslaitteen pienestä käyttäjäryhmästä johtuen markkinoilla on vain muutama versio jalkaohjauslaitteesta. Jaoimme tuotekehitysprojektin neljään vaiheeseen: käynnistäminen, luonnostelu, kehittäminen ja viimeistely. Tämän selkeytetyn työvaihejaon koimme hyväksi pohjaksi tuotekehitysprojektille. Käynnistämisvaiheessa keräsimme tarvittavaa tietoa jalkaohjauslaittesta ja tutustuimme Pasi Mäkirannan kautta yhteen malliin. Teimme myös kehityskuvauksen, jolla hahmotimme itsellemme tuotekehitysprojektin kokonaisuutta. Luonnosteluvaiheessa mietimme vaihtoehtoisia ratkaisuja ja piirsimme useita luonnoksia. Halusimme painottaa laitteen suorituskykyä, huoltoa, turvallisuutta ja ulkönäköä. Kehittelyvaiheessa aloimme rakentamaan ensimmäistä prototyyppiä. Arvioimme ensimmäisen prototyypin heikkoudet ja ongelmat, joita pyrimme ratkaisemaan toista prototyyppiä rakennettaessa. Viimeistelyvaiheessa hiomme toisen prototyypin yksityiskohtia ja teimme kokoonpanokuvat ja rakennusohjeet. Tuotekehitysprojektissa jalkaohjauslaitetta rakentaessamme otimme huomioon myös seuraavia asioita: laitteen ergonomiset vaatimukset sekä pääkäyttäjäryhmien ALS:n ja CP-oireyhtymän asettamat vaatimukset ohjainlaitteelta. Jalkaohjauslaite on tarkoitettu niille käyttäjille, joille jalkaohjain on soveltuvin ohjainmuoto sähköpyörätuoliin. Vaikka käyttäjäryhmä on pieni, on jalkaohjain käyttäjälleen tärkeä väline, joka mahdollistaa itsenäisen liikumisen ja auttaa selvyitymään arjen toiminnoissa. Koimme vieneemme jalkaohjaimen tuotekehitysprojektia eteenpäin omalta osaltamme.