Jornal da UNESP, 2015, ano XXXI, n. 312

Jornal elaborado pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Molecular genetics and functional anomalies in a series of 248 Brugada cases with 11 mutations in the TRPM4 channel.

Brugada syndrome (BrS) is a condition defined by ST-segment alteration in right precordial leads and a risk of sudden death. Because BrS is often associated with right bundle branch block and the TRPM4 gene is involved in conduction blocks, we screened TRPM4 for anomalies in BrS cases. The DNA of 248 BrS cases with no SCN5A mutations were screened for TRPM4 mutations. Among this cohort, 20 patients had 11 TRPM4 mutations. Two mutations were previously associated with cardiac conduction blocks and 9 were new mutations (5 absent from ~14'000 control alleles and 4 statistically more prevalent in this BrS cohort than in control alleles). In addition to Brugada, three patients had a bifascicular block and 2 had a complete right bundle branch block. Functional and biochemical studies of 4 selected mutants revealed that these mutations resulted in either a decreased expression (p.Pro779Arg and p.Lys914X) or an increased expression (p.Thr873Ile and p.Leu1075Pro) of TRPM4 channel. TRPM4 mutations account for about 6% of BrS. Consequences of these mutations are diverse on channel electrophysiological and cellular expression. Because of its effect on the resting membrane potential, reduction or increase of TRPM4 channel function may both reduce the availability of sodium channel and thus lead to BrS.

Effects of opioids on human serotonin transporters.

The serotonin (5-hydroxtryptamine, 5-HT) system plays a role in analgesia and emesis. The aim of this study was to test whether opioids or ketamine inhibit the human 5-HT transporter and whether this increases free plasma 5-HT concentrations. HEK293 cells, stably transfected with the human 5-HT transporter cDNA, were incubated with morphine, hydromorphone, fentanyl, alfentanil, pethidine (meperidine), tramadol, ketamine, and the reference substance citalopram (specific 5-HT transporter inhibitor). The uptake of [(3)H]5-HT was measured by liquid scintillation counting. In a second series of experiments, study drugs were incubated with plasma of ten healthy blood donors and change of 5-HT plasma-concentrations were measured (ELISA). The end point was the inhibition of the 5-HT transporter by different analgesics either in HEK293 cells or in human platelets ex vivo. Tramadol, pethidine, and ketamine suppressed [(3)H]5-HT uptake dose-dependently with an IC50 of 1, 20.9, and 230 μM, respectively. These drugs also prevented 5-HT uptake in platelets with an increase in free plasma 5-HT. Free 5-HT concentrations in human plasma were increased by citalopram 1 μM, tramadol 20 μM, pethidine 30 μM, and ketamine 100 μM to 280 [248/312]%, 269 [188/349]%, and 149 [122/174]%, respectively, compared to controls without any co-incubation (means [95 % CI]; all p < 0.005). No change in both experimental settings was observed for the other opioids. Tramadol and pethidine inhibited the 5-HT transporter in HEK293 cells and platelets. This inhibition may contribute to serotonergic effects when these opioids are given in combination, e.g., with monoamine oxidase inhibitors or selective serotonin reuptake inhibitors.

Randbemerkungen "zu dem Raschi-Commentar" : (vgl. Augustheft S. 312 fg.)

Klein

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 248 - Zusendung einer Übersicht der amerikanischen Fonds

2 Seiten

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 312 - Zusendung an Professor Hugo von Meltzl einer Abhandlung zu den Schopenhauer-Portraits

u.a.: Wilhelm Gwinner; Arthur Schopenhauer;

Ms.Ff.F.Stoltze 3. 248 - Brief von Valentin Rausch an Friedrich Stoltze

Sachsenhausen: Schulpedellen-Stelle, Stoltze: Bittschrift

Ms.Ff.F.Stoltze 3. 312 - Brief von Jakob Stern an Friedrich Stoltze

Übersendung eines Gedichts (von Abelein) für die Frankfurter Latern, Übersendung einer eigenen Schrift unter dem Pseudonym "Dr.W.Rubens"

Na 1 Nachlass Max Horkheimer, 559 - Korrespondenzen mit Leo Löwenthal (p. VI 25, 1-248)

124 Briefe zwischen Leo Löwenthal und Max Horkheimer; 1 Brief von Leo Löwenthal an Theodor W. Adorno, 29.12.1954; 2 Briefe zwischen Max Horkheimer und Marjorie Fiske, 1954/1955; 2 Briefe zwischen Leo Löwenthal und Frederick Ungar, Oktober 1954; 2 Briefe zwischen Daniel Lerner und Leo Löwenthal, Oktober 1954; 3 Briefe zwischen Leo Löwenthal und Herbert Blumer, Oktober 1954; 1 Brief von Alice H. Maier an H. P. Edelman, 10.06.1954; 2 Briefe von Leo Löwenthal an The Trustes of Hermann Weil Memorial Foundation (New York), 27.04.1955; 1 Brief von Max Horkheimer an The Trustes of Hermann Weil Memorial Foundation (New York), Juni 1954; 4 Briefe zwischen Leo Löwenthal und Chauncy D. Harris, 1954/1955; 2 Briefe zwischen John I. Kirkpatrick und Leo Löwenthal, 1954; 3 Briefe zwischen Leo Löwenthal und R. Wendell Harrison, Mai 1954; 2 Briefe von Leo Löwenthal an Gustave E. von Grunebaum, 1954; 1 Brief von Leo Löwenthal an Morton Grodzins, 12.05.1954; 2 Briefe von Max Horkheimer an Charles Y. Glock, 1954; 1 Brief von Jeremiah Kaplan an Leo Löwenthal, 15.03.1954; 2 Briefe zwischen Leo Löwenthal und Max Rheinstein, März 1954; 1 Brief von Frederick Pollock an Max Rheinstein, [1954];

Ausst. 248 - Ḥuqat hap-pesaḥ. Ritus et celebratio phase iudeo[rum], cum orationibus eor[um], [et] benedictionibus mense ad littera[m] interp[re]tatis, cum omni obseruatione vti soliti su[n]t suu[m] pasca extra terra[m] p[ro]missionis sine esu agni pascalis celebrare

Per egrediu[m] doctorem. Thoma[m] murner ex hebreo in latinu[m] traducta eloquium

Ms. lat. oct. 248 - Dienstbuch des Bartolomeo Morosini

Vorbesitzer: Bartolomeo Morosini