Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
This episode: Bacteria have repeatedly captured and used the tails of phages to fight each other!
(9 MB, 9.8 minutes)
Show notes:
Journal Paper:
Hockett KL, Renner T, Baltrus DA. 2015.
When I first heard about chirps many years ago, none of the clinical ABR systems had chirps as stimuli. As time went on, some of the manufacturers began to introduce chirps. As with any other new development, they were heavily promoted. However, I was not going to start using a new type of stimulus when the existing stimuli - traditional tone bursts and clicks - worked just fine. I kept an open mind, but I looked for evidence. Today, there is plenty of evidence for the use of chirps.
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The protein kinase C (PKC) signaling system plays a role in mood disorders and PKC inhibitors such as endoxifen may be an innovative medicine for bipolar disorder (BP) patients. In this study we show for the first time the antimanic properties of endoxifen in patients with bipolar I disorder (BPD I) with current manic or mixed episode. In a double-blind, active-controlled study, 84 subjects with BPD I were randomly assigned to receive endoxifen (4 mg/day or 8 mg/day) or divalproex in a 2:1 ratio. Patients orally administered 4 mg/day or 8 mg/day endoxifen showed significant improvement in mania assessed by the Young Mania Rating Scale as early as 4 days. The effect remained significant throughout the 21-day period. At study end point, response rates were 44.44% and 64.29% at 4 mg/day and 8 mg/day of endoxifen treatment, respectively. Thus, endoxifen has been shown as a promising novel antimanic or mood stabilizing agent.
To determine the bioequivalence of brivaracetam oral tablet formulations (10, 75, and 100 mg) versus 50 mg oral tablet and to compare the bioavailability of brivaracetam 100 mg intravenous (i.v.) bolus versus 50 and 100 mg tablets, in healthy participants.
Phase 1, randomized, open-label, five-period crossover study. Participants received five single doses of brivaracetam: 10, 50 (reference), 75, and 100 mg oral tablets; 100 mg, i.v., bolus injection. Pharmacokinetic parameters (maximum plasma concentration [Cmax], area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration [AUCt], area under the plasma concentration-time curve extrapolated to infinity [AUCinf]) were compared using analysis of variance (ANOVA) following dose normalization and logarithmic transformation. Bioavailability comparisons were based on the 90% confidence intervals (CIs) around the geometric least squares mean ratios (test: reference).
Twenty-five participants were randomized. The 90% CIs around Cmax, AUCt, and AUCinf ratios for brivaracetam 10, 75, and 100 mg tablets versus 50 mg tablet were entirely contained within the bioequivalence limits (0.8000–1.2500). For brivaracetam 100 mg, i.v., bolus, bioequivalence versus 50 and 100 mg tablets was met for AUCt and AUCinf, but Cmax was partly outside the limits (90% CI: 1.1867–1.3863 and 1.1222–1.3136, respectively).
Brivaracetam 10, 75, and 100 mg tablets were bioequivalent to the 50 mg tablet. Brivaracetam 100 mg, i.v., bolus had bioavailability similar to that of 50 and 100 mg tablets.
Vigabatrin is a highly effective antiseizure medication, but its use is limited due to concerns about retinal toxicity. One proposed mechanism for this toxicity is vigabatrin-mediated reduction of taurine. Herein we assess plasma taurine levels in a retrospective cohort of children with epilepsy, including a subset receiving vigabatrin. All children who underwent a plasma amino acid analysis as part of their clinical evaluation between 2006 and 2015 at Stanford Children's Health were included in the analysis. There were no significant differences in plasma taurine levels between children taking vigabatrin (n = 16), children taking other anti-seizure medications, and children not taking any anti-seizure medication (n = 556) (analysis of variance [ANOVA] p = 0.841). There were, however, age-dependent decreases in plasma taurine levels. Multiple linear regression revealed no significant association between vigabatrin use and plasma taurine level (p = 0.87) when controlling for age. These results suggest that children taking vigabatrin maintain normal plasma taurine levels, although they leave unanswered whether taurine supplementation is necessary or sufficient to prevent vigabatrin-associated visual field loss. They also indicate that age should be taken into consideration when evaluating taurine levels in young children.
TREK1 (Twik-RElated Potassium (K+) channel 1), though a well characterized target for several neuropsychiatric disorders, underwent very few explorations for prototypic inhibitors. This study aimed to find diverse chemotypes by an in silico means. Homology-built TREK1 on docking with high affinity quaternary ammonium compounds (QAs) corroborated the previous findings by recreating the binding mode with proximally positioned key residues: Thr157, Thr266, Ile182, Leu189, and Leu304. Physical interactions between TREK1 and known antagonists were modeled to compensate the lack of ligand-bound protein crystal structures. A common feature hypothesis (Hypo1) was deduced from the chemical features of 6 active compounds. Validated Hypo1 and the most potent compound in the data set were employed as pharmacophore- and similarity-based virtual screening queries respectively. 33 hit compounds were tested for their ability to block TREK1 currents in HEK-293 transfected cells using whole-cell patch-clamp recording. 11 candidates displayed dose-dependent inhibition of channel currents, among these, NC30 possessing a 4-((1H-pyrrolo[2,3-b]pyridin-1-yl)methyl)piperidin-4-ol heterocyclic core was the most potent one with an IC50 of 4.7 μM. These results form a rational basis to design future drugs and this is the first report of novel TREK1 antagonists delineated by a synergistic application of structure- and ligand-based approaches.
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In silico identification of novel TREK 1 antagonists.
Cerebrovascular stroke is a main cause of lasting disability in older age, and initial stroke severity has been established as a main determinant for the degree of functional loss. In this study, we searched for other predictors of functional outcome in a cohort of stroke patients participating in an early supported discharge randomised controlled trial.
Thirty candidate variables related either to premorbid history or to the acute stroke were examined by ordered logistic regression in 229 stroke patients. Dependent variables were modified Rankin Scale (mRS) at 6 months and mRS change from baseline to 6 months.
For mRS at 6 months, Barthel Index at stable baseline post-stroke was the main predictor, with sex, age, previous cerebrovascular disease, previous peripheral artery disease and the necessity for tube feeding in the acute phase also contributing to the final model. For mRS change, only age and previous cerebrovascular disease were significant predictors. Prestroke subjective health complaints added significantly to all final models concurrently with sex losing its predictive power.
Initial stroke severity was the main predictor of functional outcome. Subjective health complaints score was a potent predictor for both outcome and improvement from baseline to 6 months and at the same time ameliorated the predictive impact of sex. The poorer functional prognosis for women after stroke may therefore be related to their higher load of subjective health complaints rather than to their sex itself. Treating these complaints may possibly improve the functional prognosis.
