Substitution of (R,S)-methadone by (R)-methadone: Impact on QTc interval.

Methadone is administered as a chiral mixture of (R,S)-methadone. The opioid effect is mainly mediated by (R)-methadone, whereas (S)-methadone blocks the human ether-à-go-go-related gene (hERG) voltage-gated potassium channel more potently, which can cause drug-induced long QT syndrome, leading to potentially lethal ventricular tachyarrhythmias. To investigate whether substitution of (R,S)-methadone by (R)-methadone could reduce the corrected QT (QTc) interval, (R,S)-methadone was replaced by (R)-methadone (half-dose) in 39 opioid-dependent patients receiving maintenance treatment for 14 days. (R)-methadone was then replaced by the initial dose of (R,S)-methadone for 14 days (n = 29). Trough (R)-methadone and (S)-methadone plasma levels and electrocardiogram measurements were taken. The Fridericia-corrected QT (QTcF) interval decreased when (R,S)-methadone was replaced by a half-dose of (R)-methadone; the median (interquartile range [IQR]) values were 423 (398-440) milliseconds (ms) and 412 (395-431) ms (P = .06) at days 0 and 14, respectively. Using a univariate mixed-effect linear model, the QTcF value decreased by a mean of -3.9 ms (95% confidence interval [CI], -7.7 to -0.2) per week (P = .04). The QTcF value increased when (R)-methadone was replaced by the initial dose of (R,S)-methadone for 14 days; median (IQR) values were 424 (398-436) ms and 424 (412-443) ms (P = .01) at days 14 and 28, respectively. The univariate model showed that the QTcF value increased by a mean of 4.7 ms (95% CI, 1.3-8.1) per week (P = .006). Substitution of (R,S)-methadone by (R)-methadone reduces the QTc interval value. A safer cardiac profile of (R)-methadone is in agreement with previous in vitro and pharmacogenetic studies. If the present results are confirmed by larger studies, (R)-methadone should be prescribed instead of (R,S)-methadone to reduce the risk of cardiac toxic effects and sudden death.

Estudio de otolitos de Odonthestes regia r., Pejerrey: determinación de edad

El estudio de los incrementos marginales de crecimiento mensual de otolitos de pejerrey , sugiere: Un inicio de formación de anillo para el mes de julio y otra formación para enero; ambos se encuentran relacionados al ápice y secundario del desove. La regresión que relaciona la longitud del pez (cm) con la longitud del otolito (mm) corresponde a: Y=2 .302 + 7.72163 X, R=0. 99, N=427 especímenes . La distribución mensual de longitudes del total de pe­ces N=798, sugiere que hay una reducción del tamaño modal después de abril con una alta proporción de peces menores de 15 cm y ésto alcanza su máximo más o menos entre julio y setiembre. Este cambio puede significar que el reclutamiento tomaría lugar entre mayo y octubre con el ápice en agosto. La madurez sexual , estudio de la distribución porcentual por estadios a lo largo de todos los meses del año 1975, Sugiere: considerando los estadíos V, VI, VII juntos y el VI separadamente, que el ápice del desove es en julio con un rango entre mayo y octubre y con un ápice secundario en enero. El contaje de anillos anuales en la estructura de los otolitos nos dice que esta especie es de vida corta no más de tres años. La ecuación de crecimiento de von Bertalanf fy corresponde)

TACI, unlike BAFF-R, is solely activated by oligomeric BAFF and APRIL to support survival of activated B cells and plasmablasts.

The cytokine BAFF binds to the receptors TACI, BCMA, and BAFF-R on B cells, whereas APRIL binds to TACI and BCMA only. The signaling properties of soluble trimeric BAFF (BAFF 3-mer) were compared with those of higher-order BAFF oligomers. All forms of BAFF bound BAFF-R and TACI, and elicited BAFF-R-dependent signals in primary B cells. In contrast, signaling through TACI in mature B cells or plasmablasts was only achieved by higher-order BAFF and APRIL oligomers, all of which were also po-tent activators of a multimerization-dependent reporter signaling pathway. These results indicate that, although BAFF-R and TACI can provide B cells with similar signals, only BAFF-R, but not TACI, can respond to soluble BAFF 3-mer, which is the main form of BAFF found in circulation. BAFF 60-mer, an efficient TACI agonist, was also detected in plasma of BAFF transgenic and nontransgenic mice and was more than 100-fold more active than BAFF 3-mer for the activation of multimerization-dependent signals. TACI supported survival of activated B cells and plasmablasts in vitro, providing a rational basis to explain the immunoglobulin deficiency reported in TACI-deficient persons.

Handkarta öfver Finland för skolorna af R. Hult

1 kartta :, vär. ;, 62,8 x 46,5 cm, lehti 71 x 55 cm

Karta öfver storfurstendömet Finland efter nya tillförlitliga källor och med särskildt begagnande af general stabens original-kartor utgiftven år 1860 af öfverste Georg Alfthan /

1 kartta :, vär. ;, 72,5 x 47,4 cm, lehti 83 x 58 cm

Теченїе Невы рѣки изъ Ладожскаго озера къ Ст. Петербургу / Tetšenïe Nevy rěki iz Ladožskago ozera k St. Peterburgu = Fluvius Newa a Lacu Ladoga Petropolin versus procurrens

Mittakaava 1:105000

Charta öfver Österbotten och Caianebo[r]gs län

1 kartta : käsinpiirros, vär. ; 54 x 43,5 cm, lehti 59,5 x 47 cm. Mittakaavaa ei määritelty. Pahville liimattu.

Kartor och beskrifningar öfver socknarne i Nylands län / upprättade å general landmäteri kontoret, lithografierade och utgifne till granskning och berigtigande år 1844.

1 kartasto ([35] s., [24] karttalehteä (7 taitettuina)) : 24 karttaa, vär. ; 56 cm

Geographisk charta öfver Helsingfors stad med dess närmäste belägenhet efter högvälborne Herr generalen och commend: Ehrnsvärlds befallning år 1763

Kopia

Karta öfver Uleåborgs stad upprättad år 1886 i enlighet med af aflidne Civil-Ingenieur C. Kjerrström år 1876 öfver staden upprättade karta jemte tilläg af: G. Wilh. Liljeblad

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Plan af Nystad utgifven år 1843 af C. W. Gyldén

Uudenkaupungin kartta. - 1 kartta : vär. ; 39,5 x 55,4 cm, lehti 45 x 60 cm. - Mittakaava [1:8000]. - Sisältää luettelot kortteleista ja julkisista rakennuksista.

Plan af Helsingfors år 1859

Kartan esitystekniikka: maastokartta

Karta öfver Björneborgs stad upprättad år 1895 af F. J. Lindström

Liittyy julkaisuun Björneborgs stads historia / J. W. Ruuth

Karta öfver Åbo stad enligt gamla plan och nya regleringen år 1828

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