Pilot study of the SPRINT glycemic control protocol in a Hungarian medical intensive care unit.

Stress-induced hyperglycemia increases morbidity and mortality. Tight control can reduce mortality but has proven difficult to achieve. The SPRINT (Specialized Relative Insulin and Nutrition Tables) protocol is the only protocol that reduced both mortality and hypoglycemia by modulating both insulin and nutrition, but it has not been tested in independent hospitals. SPRINT was used for 12 adult intensive care unit patients (949 h) at Kálmán Pándy Hospital (Gyula, Hungary) as a clinical practice assessment. Insulin recommendations (0-6 U/h) were administered via constant infusion rather than bolus delivery. Nutrition was administered per local standard protocol, weaning parenteral to enteral nutrition, but was modulated per SPRINT recommendations. Measurement was every 1 to 2 h, per protocol. Glycemic performance is assessed by percentage of blood glucose (BG) measurements in glycemic bands for the cohort and per patient. Safety from hypoglycemia is assessed by numbers of patients with BG < 2.2 (severe) and %BG < 3.0 and < 4.0 mmol/liter (moderate and light). Clinical effort is assessed by measurements per day. Results are median (interquartile range). There were 742 measurements over 1088 h of control (16.4 measurements/day), which is similar to clinical SPRINT results (16.2/day). Per-patient hours of control were 65 (50-95) h. Initial per-patient BG was 10.5 (7.9-11.2) mmol/liter. All patients (100%) reached 6.1 mmol/liter. Cohort BG was 6.3 (5.5-7.5) mmol/liter, with 42.2%, 65.1% and 77.6% of BG in the 4.0-6.1, 4.0-7.0, and 4.0-8.0 mmol/liter bands. Per-patient, median percentage time in these bands was 40.2 (26.7-51.5)%, 62.5 (46.0-75.7)%, and 74.7 (61.6.8-87.8)%, respectively. No patients had BG < 2.2 mmol/liter, and the %BG < 4.0 mmol/liter was 1.9%. These results were achieved using 3.0 (3.0-5.0) U/h of insulin with 7.4 (4.4-10.2) g/h of dextrose administration (all sources) for the cohort. Per-patient median insulin administration was 3.0 (3.0-3.0) U/h and 7.1 (3.4-9.6) g/h dextrose. Higher carbohydrate nutrition formulas than were used in SPRINT are offset by slightly higher insulin administration in this study. The glycemic performance shows that using the SPRINT protocol to guide insulin infusions and nutrition administration provided very good glycemic control in initial pilot testing, with no severe hypoglycemia. The overall design of the protocol was able to be generalized with good compliance and outcomes across geographically distinct clinical units, patients, and clinical practice. © 2012 Diabetes Technology Society

Probing pattern and dynamics of disulfide bridges using synthesis and NMR of an ion channel blocker peptide toxin with multiple diselenide bonds

Anuroctoxin (AnTx), a 35-amino-acid scorpion toxin containing four disulfide bridges, is a high affinity blocker of the voltage-gated potassium channel Kv1.3, but also blocks Kv1.2. To improve potential therapeutic use of the toxin, we have designed a double substituted analog, [N17A/F32T]-AnTx, which showed comparable Kv1.3 affinity to the wild-type peptide, but also a 2500-fold increase in the selectivity for Kv1.3 over Kv1.2. In the present study we have achieved the chemical synthesis of a Sec-analog in which all cysteine (Cys) residues have been replaced by selenocysteine (Sec) forming four diselenide bonds. To the best of our knowledge this is the first time to replace, by chemical synthesis, all disulfide bonds with isosteric diselenides in a peptide/protein. Gratifyingly, the key pharmacological properties of the Sec-[N17A/F32T]-AnTx are retained since the peptide is functionally active. We also propose here a combined experimental and theoretical approach including NOE- and Se-77-based NMR supplemented by MD simulations for conformational and dynamic characterization of the Sec-[N17A/F32T]-AnTx. Using this combined approach allowed us to attain unequivocal assignment of all four diselenide bonds and supplemental MD simulations allowed characterization of the conformational dynamics around each disulfide/diselenide bridge

Heck-oxyarylation of 2-phenyl-2H-chromenes and 1,2-dihydronaphthalenes

The Heck-oxyarylation of racemic 2-phenyl-2H-chromene [(±)-4b] and 1,2-dihydronaphthalenes (14a,b) has been studied with 2-chloromercuriphenols (5a–d) in the presence of Li2[PdCl4] catalyst. The reactions resulted in the diastereoselective formation of racemic 6- phenylpterocarpans of (6R, 6aR,11aR) relative configuration [(±)-8a–d] and their dibenzo[1,3]dioxocine analogues [(±)-12a–d] as main products, respectively. The ratio of products and the lack of regioisomeric products (13a–d) corroborated the cationic mechanism of the oxyarylation of 2H-chromenes, which has been also supported by the transformation of 14a,b under similar conditions.(doi: 10.5562/cca2103

Exploring the Syntheses of Novel Glycomimetics: Carbohydrate Derivatives with Se-S- or Se-Se- Glycosidic Linkages

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Miscellanea. Levelek a szerkesztőhöz. Folyóirat-referátumok

Levelek a szerkesztőhöz. | Folyóirat-referátumok. Gerontológia A földre leülés és felállás képessége a bármely okú halálozás előrejelzője (Ability to sit and rise from the floor as a predictor of all-cause mortality) de Brito, L. B., Ricardo, D. R., de Araújo, D. S. et al. (Levelező szerző: Claudio Gil Soares de Araújo, Clinimex Rua Siqueira Campos, 93/101, 22031-070, Rio de Janeiro, Brazília; e-mail: [email protected].): Eur. J. Prev. Cardiol., 2014, 21 (7), 892–898. | Kardiológia A nem szteroid gyulladáscsökkentők (NSAID-ok) cardiovascularis hatásai: okozhatnak-e jelentős vérnyomás- emelkedést az NSAID-ok? [Cardiovascular effects of NSAIDs: Do nonsteroidal anti-inflammattory drugs (NSAIDs) cause a clinically significant increase in blood pressure?] Sherve, K., Gerard, C. J., Neher, J. O., et al. (Valley Family Medicine Residency, Renton, WA, Amerikai Egyesült Államok; e-mail: [email protected]): Am. Fam. Physician, 2014, 90 (4), online | Szülészet-nőgyógyászat Ultrahang a 3. trimeszterben (Ultraschall im 3. trimenon) Schmitz, R. (Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Münster, e-mail: [email protected]): Geburtsch. Frauenheilk., 2013, 73 (1), 42–45

Photochemical and Structural Studies on Cyclic Peptide Models

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Probing pattern and dynamics of disulfide bridges using synthesis and NMR of an ion channel blocker peptide toxin with multiple diselenide bonds

Anuroctoxin (AnTx), a 35-amino-acid scorpion toxin contg. four disulfide bridges, is a high affinity blocker of the voltage-gated potassium channel Kv1.3, but also blocks Kv1.2. To improve the potential therapeutic use of the toxin, we have designed a double substituted analog, [N17A/F32T]-AnTx, which showed comparable Kv1.3 affinity to the wild-type peptide, but 2500-fold increase in the selectivity for Kv1.3 over Kv1.2. In the present study we have achieved the chem. synthesis of a Sec-analog in which all cysteine (Cys) residues have been replaced by selenocysteine (Sec) forming four diselenide bonds. To the best of our knowledge this is the first time to replace, by chem. synthesis, all disulfide bonds with isosteric diselenides in a peptide/protein. Gratifyingly, the key pharmacol. properties of the Sec-[N17A/F32T]-AnTx are retained since the peptide is functionally active. We also propose here a combined exptl. and theor. approach including NOE- and 77Se-based NMR supplemented by MD simulations for conformational and dynamic characterization of the Sec-[N17A/F32T]-AnTx. The use of such combined approach allowed us to attain unequivocal assignment of all four diselenide bonds and supplemental MD simulations allowed to characterize the conformational dynamics around each disulfide/diselenide bridge. [on SciFinder(R)