Berlin 2/12 -31

Kirje 2.12.1931

Hki 2/9 1943

Kirje 2.9.1943

Eduskunta 29/2 1944

Kirje 29.2.1944

Helsinki 28.2.1932

Kirje

Helsinki 2.9.1924

Kirje

Angervonniemi 2.8.1936

Kirje

Helsinki 2/3 1940.

Kirje

Comparative effects of teriparatide and ibandronate on spine bone mineral density (BMD) and microarchitecture (TBS) in postmenopausal women with osteoporosis: a 2-year open-label study.

Treatment effects over 2 years of teriparatide vs. ibandronate in postmenopausal women with osteoporosis were compared using lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). Teriparatide induced larger increases in BMD and TBS compared to ibandronate, suggesting a more pronounced effect on bone microarchitecture of the bone anabolic drug. INTRODUCTION: The trabecular bone score (TBS) is an index of bone microarchitecture, independent of bone mineral density (BMD), calculated from anteroposterior spine dual X-ray absorptiometry (DXA) scans. The potential role of TBS for monitoring treatment response with bone-active substances is not established. The aim of this study was to compare the effects of recombinant human 1-34 parathyroid hormone (teriparatide) and the bisphosphonate ibandronate (IBN), on lumbar spine (LS) BMD and TBS in postmenopausal women with osteoporosis. METHODS: Two patient groups with matched age, body mass index (BMI), and baseline LS BMD, treated with either daily subcutaneous teriparatide (N̴1;=̴1;65) or quarterly intravenous IBN (N̴1;=̴1;122) during 2 years and with available LS BMD measurements at baseline and 2 years after treatment initiation were compared. RESULTS: Baseline characteristics (overall mean ± SD) were similar between groups in terms of age 67.9̴1;±̴1;7.4 years, body mass index 23.8̴1;±̴1;3.8 kg/m(2), BMD L1-L4 0.741̴1;±̴1;0.100 g/cm(2), and TBS 1.208̴1;±̴1;0.100. Over 24 months, teriparatide induced a significantly larger increase in LS BMD and TBS than IBN (+7.6 %̴1;±̴1;6.3 vs. +2.9 %̴1;±̴1;3.3 and +4.3 %̴1;±̴1;6.6 vs. +0.3 %̴1;±̴1;4.1, respectively; P̴1;<̴1;0.0001 for both). LS BMD and TBS were only weakly correlated at baseline (r (2)̴1;=̴1;0.04) with no correlation between the changes in BMD and TBS over 24 months. CONCLUSIONS: In postmenopausal women with osteoporosis, a 2-year treatment with teriparatide led to a significantly larger increase in LS BMD and TBS than IBN, suggesting that teriparatide had more pronounced effects on bone microarchitecture than IBN.

Postmenopausal circulating levels of 2- and 16α-hydroxyestrone and risk of endometrial cancer.

Background:It has been suggested that the relative importance of oestrogen-metabolising pathways may affect the risk of oestrogen-dependent tumours including endometrial cancer. One hypothesis is that the 2-hydroxy pathway is protective, whereas the 16α-hydroxy pathway is harmful.Methods:We conducted a case-control study nested within three prospective cohorts to assess whether the circulating 2-hydroxyestrone̴1;:̴1;16α-hydroxyestrone (2-OHE1̴1;:̴1;16α-OHE1) ratio is inversely associated with endometrial cancer risk in postmenopausal women. A total of 179 cases and 336 controls, matching cases on cohort, age and date of blood donation, were included. Levels of 2-OHE1 and 16α-OHE1 were measured using a monoclonal antibody-based enzyme assay.Results:Endometrial cancer risk increased with increasing levels of both metabolites, with odds ratios in the top tertiles of 2.4 (95% CI=1.3, 4.6; P(trend)=0.007) for 2-OHE1 and 1.9 (95% CI=1.1, 3.5; P(trend)=0.03) for 16α-OHE1 in analyses adjusting for endometrial cancer risk factors. These associations were attenuated and no longer statistically significant after further adjustment for oestrone or oestradiol levels. No significant association was observed for the 2-OHE1̴1;:̴1;16α-OHE1 ratio.Conclusion:Our results do not support the hypothesis that greater metabolism of oestrogen via the 2-OH pathway, relative to the 16α-OH pathway, protects against endometrial cancer.

Nedd4-2 ubiquitin ligase: a contributor to experimental neuropathic pain?

Background: Neuropathic pain is associated with altered expression of voltage-gated sodium channels (VGSCs) leading to peripheral nerve hyperexcitability. Interestingly, in cell expression systems, the ubiquitin ligase Nedd4-2 regulates the cell membrane density of the most abundant peripheral and pain-related VGSC, namely Nav1.7, and decreases its sodium current. Yet nothing is known about the involvement of Nedd4-2 in nociception and chronic pain. Therefore, the goal of this study is (i) to characterize Nedd4-2 and Nav1.7 expression in an experimental model of neuropathic pain (ii) to design by viral vector-mediated gene therapy an approach to depict the implication of Nedd4-2 in chronic pain. Methods: Western Blot and immunohistochemistry experiments detecting Nav1.7 and Nedd4-2 were performed in rodent DRGs 7 days after spared nerve injury (SNI). For the viral vector-mediated gene therapy, a recombinant Adeno-Associated Virus (rAAV2/6) was generated expressing the Nedd4-2 gene. Intrathecal injection of rAAV2/6 was followed 2 weeks after by the SNI surgery. Data are expressed in mean ± SEM, n = 4 in each condition. Results: Immunofluorescence on DRGs neurons reveals a decreased number of positive Nedd4-2 cells in the SNI model (27.0 ± 1.2%) versus sham group (43.4 ± 3.5%; p <0.005), as well as an increase in positive Nav1.7 cells in SNI (50.1 ± 2.9%) versus Sham (41.6 ± 1.8%; p <0.05). The change of Nedd4-2 expression was confirmed by western-blot analysis. In addition, we show that Nedd4-2 and Nav1.7 are largely expressed in overlapping cell populations, chiefly colocalizing with markers of small nociceptive neurons. Furthermore, we report that intrathecal injection of rAAV is able to counteract the reduction of Nedd4-2 expression in SNI animals. Conclusion: Our results indicate that Nedd4-2 is mainly expressed in nociceptors and downregulated after nerve injury. Moreover, our data suggest that the reduction of Nedd4-2, after nerve injury, may modulate Nav1.7 activity and contribute to hyperexcitability in neuropathic pain. A normal level of Nedd4-2 can be restored using a viral vector and we will further assess its functional effect on pain sensitivity.

Ablation of human colon carcinoma in nude mice by 131I-labeled monoclonal anti-carcinoembryonic antigen antibody F(ab')2 fragments.

Pooled F(ab')2 fragments of three MAbs against distinct epitopes of carcinoembryonic antigen (CEA) were used for radioimmunotherapy of nude mice bearing a subcutaneous human colon carcinoma xenograft. 9-10 d after transplantation when tumor nodules were in exponential growth, 36 mice were treated by intravenous injection of different amounts of 131I-labeled MAb F(ab')2. All 14 mice injected with a single dose of 2,200 (n = 10) or 2,800 microCi (n = 4) showed complete tumor remission. 8 of the 10 mice treated with 2,200 microCi survived in good health for 1 yr when they were killed and shown to be tumor free. Four of nine other mice treated with four fractionated doses of 400 microCi showed no tumor relapse for more than 9 mo. In contrast, all 15 mice injected with 1,600-3,000 microCi 131I-control IgG F(ab')2 showed tumor growth retardation of only 1-4 wk, and 15 of 16 mice injected with unlabeled anti-CEA MAb F(ab')2 showed unmodified tumor progression as compared with untreated mice. From tissue radioactivity distributions it was calculated that by an injection of 2,200 microCi 131I-MAb F(ab')2 a mean dose of 8,335 rad was selectively delivered to the tumor, while the tissue-absorbed radiation doses for the normal organs were: peripheral blood, 2,093; stomach, 1,668; kidney, 1,289; lung, 1,185; liver, 617; spleen, 501; small intestine, 427; large intestine, 367; bone, 337; and muscle, 198. These treatments were well tolerated since out of 19 mice with complete tumor remission only 4 required bone marrow transplantation and 17 were in good health for 6-12 mo of observation. The results demonstrate the selective destruction of established human colon carcinoma transplants by intravenous injection of either single or fractionated doses of 131I-MAb F(ab')2.

CEVADA BR 2: CULTIVAR DE CEVADA CERVEJEIRA RESISTENTE À MANCHA-RETICULAR CAUSADA POR PYRENOPHORA TERES

A Cevada BR 2, criada pela Embrapa-Centro Nacional de Pesquisa de Trigo (CNPT), foi lançada para cultivo em 1989. Originou-se de sete plantas selecionadas em F3 do cruzamento FM 424/TR 206, realizado em 1979, em Passo Fundo, RS. A BR 2 é uma cevada de primavera, do tipo de duas fileiras de grãos, com ciclo precoce, ampla adaptação e porte baixo. É a primeira cultivar brasileira resistente a Pyrenophora teres, agente causal da mancha-reticular, principal moléstia da cevada no Brasil. Em oito anos de avaliação no Ensaio Nacional de Cevada, conduzido em 12 locais da Região Sul, a BR 2 rendeu entre 1.621 e 4.014 kg/ha de grãos de primeira qualidade, superando a cultivar Antarctica 05 em 3% no RS e SC, em 13% no PR, e em 6% na média dos 96 experimentos (12 locais x 8 anos). Na lavoura, a BR 2 tem produzido rendimentos acima de 5.000 kg/ha. Aprovada como cervejeira em 1992, ocupou 30% da área semeada em 1993 e 90% em 1997. A BR 2 representa um marco no progresso do melhoramento genético da cevada no país, contribuindo decisivamente para o aumento da competitividade da produção doméstica.

Bonded, Thin-Lift, Non-Reinforced Portland Cement Concrete Resurfacing, MLR-77-2, 1977

A research project involving 2, 3, 4, and 5 in. (5.1, 7.6, 10.2, and 12.7 cm) of bonded portland cement concrete (PCC) overlay on a 1.3 mile (2.1 km) PCC pavement was conducted in Clayton County, Iowa, during September 1977, centering on the following objectives: (1) Determine the mixing and proportioning procedures required in using a conventional, central mix proportioning plant to produce a dense PCC mixture using standard mixes with super water reducing admixtures; (2) Determine the economics, longevity and maintenance performance of a bonded, thin-lift, non-reinforced PCC resurfacing course using conventional procedures, equipment and concrete paving mixtures both with and without super water reducing admixtures; and (3) Determine if an adequate bond between the existing pavement and an overlay of thin-lift, dense, non-reinforced PCC can be obtained with only special surface cleaning and no surface removal or grinding. The conclusions are as follows: (1) Normal mixing equipment and proportioning procedures could be used using a conventional central-mix proportioning plant. This was successful when used with super water reducing admixtures. Only minor changes need be made in procedures and timing. (2) The time has been too short since the completion of the project to determine how the new pavement will perform, however, initially it appears that the method is economical and no reason is seen at this time why the life of the pavement should not be comparable to an all new pavement. (3) The initial test results show that bond strength, regardless of which method of cleaning is used, scarifying, sand blasting or water blasting, far exceed what is considered the minimum bond strength of 200 psi (1379 kPa) except where the paint stripes were intentionally left, thus showing that the paint must be removed. (4) It appears that either cement and water grout or sand, cement and water grout may be used and still obtain the required bond.

Determination of the enantiomers of thioridazine, thioridazine 2-sulfone, and of the isomeric pairs of thioridazine 2-sulfoxide and thioridazine 5-sulfoxide in human plasma.

Thioridazine is a commonly prescribed phenothiazine drug administered as a racemate and it is believed that its antipsychotic effect is mainly associated with (R)-thioridazine. A method based on high-performance liquid chromatography has been developed for the determination of the enantiomers of thioridazine and thioridazine 2-sulfone (THD 2-SO2 or sulforidazine) and of the enantiomers of the diastereoisomeric pairs of thioridazine 2-sulfoxide (THD 2-SO or mesoridazine) and thioridazine 5-sulfoxide (THD 5-SO) in the plasma of thioridazine-treated patients. The method involves sequential achiral and chiral HPLC. The limits of quantitation for total (R) + (S) concentrations were found to be 15 ng/ml for thioridazine and 5 ng/ml for its metabolites. The limits for the determination of the (R)/(S) ratios were found to be 60 ng/ml for racemic THD and 10 ng/ml for racemic THD 2-SO, THD 2-SO2, THD 5-SO (FE) and THD 5-SO (SE). The method has been used to determine the concentrations of the enantiomers of thioridazine and of its metabolites in the plasma of a patient treated with 100 mg of racemic thioridazine hydrochloride per os per day for 14 days. The results show a high enantioselectivity in the metabolism of this drug: the (R)/(S) ratios for THD, THD 2-SO (FE), THD 2-SO (SE), THD 2-SO2, THD 5-SO (FE) and THD 5-SO (SE) were found to be 3.90, 1.22, 6.10, 4.10, 0.09 and 28.0, respectively.