- Gains and losses of metabolic function inferred from a phylotranscriptomic analysis of algae. [Journal Article]
- SRSci Rep 2019 Jul 19; 9(1):10482
- Hidden Markov models representing 167 protein sequence families were used to infer the presence or absence of homologs within the transcriptomes of 183 algal species/strains. Statistical analyses of …
Hidden Markov models representing 167 protein sequence families were used to infer the presence or absence of homologs within the transcriptomes of 183 algal species/strains. Statistical analyses of the distribution of HMM hits across major clades of algae, or at branch points on the phylogenetic tree of 98 chlorophytes, confirmed and extended known cases of metabolic loss and gain, most notably the loss of the mevalonate pathway for terpenoid synthesis in green algae but not, as we show here, in the streptophyte algae. Evidence for novel events was found as well, most remarkably in the recurrent and coordinated gain or loss of enzymes for the glyoxylate shunt. We find, as well, a curious pattern of retention (or re-gain) of HMG-CoA synthase in chlorophytes that have otherwise lost the mevalonate pathway, suggesting a novel, co-opted function for this enzyme in select lineages. Finally, we find striking, phylogenetically linked distributions of coding sequences for three pathways that synthesize the major membrane lipid phosphatidylcholine, and a complementary phylogenetic distribution pattern for the non-phospholipid DGTS (diacyl-glyceryl-trimethylhomoserine). Mass spectrometric analysis of lipids from 25 species was used to validate the inference of DGTS synthesis from sequence data.
- In vivo evaluation of solid lipid microparticles and hybrid polymer-lipid microparticles for sustained delivery of leuprolide. [Journal Article]
- EJEur J Pharm Biopharm 2019 Jul 09
- This study aims to investigate the potential of solid lipid microparticles (MP) and hybrid polymer-lipid MPs for sustained delivery of a peptide drug, leuprolide. A peptide-phospholipid complex was p…
This study aims to investigate the potential of solid lipid microparticles (MP) and hybrid polymer-lipid MPs for sustained delivery of a peptide drug, leuprolide. A peptide-phospholipid complex was prepared to increase the compatibility of the peptide with triglyceride (TG) and poly (lactide-co-glycolide) (PLGA). Peptide loaded solid lipid MPs, PLGA MPs, and hybrid MPs were prepared using a spray drying method and characterized in terms of particle size, morphology and encapsulation efficiency. The pharmacokinetics and pharmacodynamics of leuprolide after subcutaneous injection of spray-dried MPs were evaluated in rats. Spray-dried MPs were spherical ranging in size from 4 μm to 10 μm, which are suitable for injection. After subcutaneous administration of reconstituted MPs, leuprolide could be detected in plasma samples of rats for one to two months, depending on the formulation and dose. Sustained release of leuprolide from PLGA MPs and glyceryl tristearate (TG18) MPs was observed over one month, with a chemical castration effect of 25 and 30 days, respectively. The bioavailability of leuprolide from PLGA-TG18 hybrid MPs was approximately four times higher than that from TG18 MP and PLGA MP alone using the same dose of leuprolide (6 mg/kg). Chemical castration in rats was observed over 30 and 60 days after injection of the PLGA-TG18 hybrid MP with a dose of 3 mg/kg and 6 mg/kg leuprolide, respectively. Additionally, a much lower Cmax was observed for the hybrid MP group. In conclusion, spray-dried PLGA-triglyceride hybrid MPs can be used as better carriers than other MPs for subcutaneous delivery of peptide drugs due to the synergetic effect of lipids and PLGA for sustained drug release from the spray-dried MP.
- Targeting CGRP via receptor antagonism and antibody neutralisation in two distinct rodent models of migraine-like pain. [Journal Article]
- CCephalalgia 2019 Jul 09; :333102419861726
- CONCLUSIONS: The current data clearly show that calcitonin gene-related peptide-mediated signaling is critically involved in the manifestation of cutaneous hypersensitivity in distinct rodent models of migraine-like pain and emphasise their translational relevance. Moreover, the unexpected rapidity of onset observed for ALD405 supports i) a probable site of action outside the blood-brain barrier, and ii) a potential clinical utility of specific monoclonal calcitonin gene-related peptide antibodies in the abortive treatment of migraine.
- Regioselective Ring-Opening of Glycidol to Monoalkyl Glyceryl Ethers Promoted by an [OSSO]-FeIII Triflate Complex. [Journal Article]
- CChemSusChem 2019 Jul 08
- A FeIII -triflate complex, bearing a bis-thioether-di-phenolate [OSSO]-type ligand, was discovered to promote the ring-opening of glycidol with alcohols under mild reaction conditions (0.05 mol % cat…
A FeIII -triflate complex, bearing a bis-thioether-di-phenolate [OSSO]-type ligand, was discovered to promote the ring-opening of glycidol with alcohols under mild reaction conditions (0.05 mol % catalyst and 80 °C). The reaction proceeded with high activity (initial turnover frequency of 1680 h-1 for EtOH) and selectivity (>95 %) toward the formation of twelve monoalkyl glyceryl ethers (MAGEs) in a regioselective fashion (84-96 % yield of the non-symmetric regioisomer). This synthetic approach allows the conversion of a glycerol-derived platform molecule (i.e., glycidol) to high-value-added products by using an Earth-crust abundant metal-based catalyst.
- Hemodynamic and autonomic effects of low-dose glyceryl trinitrate used to test endothelium-independent vasodilation of the brachial artery. [Journal Article]
- VPVascul Pharmacol 2019 Jul 03; :106576
- Smooth muscle function is explored by sublingual glyceryl trinitrate (GTN) administration to compare with endothelium-dependent vasodilation of the brachial artery by flow-mediated-dilation (FMD). Th…
Smooth muscle function is explored by sublingual glyceryl trinitrate (GTN) administration to compare with endothelium-dependent vasodilation of the brachial artery by flow-mediated-dilation (FMD). This study compared the hemodynamic and autonomic effects of the two most often used GTN dosages. In 80 essential hypertensive patients (HT) and 60 normotensive subjects (NT), FMD of the brachial artery and endothelium-independent response to sublingual GTN (25 μg and 400 μg) were evaluated by high-resolution ultrasound and automated image analysis. In 10 HT, muscle sympathetic nerve activity (MSNA) was also assessed by microneurography. HT showed significantly (p < .01) lower FMD (5.5 ± 3.3%) compared to NT (6.9 ± 2.2%). The response to GTN 25 μg tended to be lower (HT:7.2 ± 3.3%; NT:7.9 ± 2.9%; p = .06), whereas response to GTN 400 μg was similar (HT:14.3 ± 4.8%, NT:14.5 ± 4.7%, p = ns). Blood pressure (BP) reduction induced by GTN 400 μg (systolic-BP:-3.2 ± 7.7 mm Hg, diastolic-BP:-4.7 ± 5.0 mm Hg) was greater (p < .001) compared to GTN 25 μg (systolic-BP:-0.7 ± 5.8 mm Hg, diastolic-BP:-0.7 ± 4.4 mm Hg). Changes in heart rate were also greater (+5.6 ± 6.4 bpm versus -0.2 ± 5.4 bpm, p < .001). This behaviour was similar in either NT or HT. MSNA was significantly increased by GTN 400 μg (31 ± 7bursts/min to 41 ± 6bursts/min, p < .001) but not by 25 μg (33 ± 9bursts/min to 37 ± 11bursts/min, p = .19). In conclusion, the administration of low-dose GTN allows exploring endothelium-independent vasodilation in FMD protocols, inducing only modest hemodynamic and sympathetic responses.
- Multilayer-Coated Tablet of Clopidogrel and Rosuvastatin: Preparation and In Vitro/In vivo Characterization. [Journal Article]
- PPharmaceutics 2019 Jul 04; 11(7)
- The acid lability of rosuvastatin hinders the preparation of mixed combination formulations of rosuvastatin with acidic drugs such as clopidogrel. Therefore, the purpose of this study was to develop …
The acid lability of rosuvastatin hinders the preparation of mixed combination formulations of rosuvastatin with acidic drugs such as clopidogrel. Therefore, the purpose of this study was to develop a multilayer-coated tablet that avoids physicochemical interactions between rosuvastatin and clopidogrel. Among the tested hydrophobic materials, glyceryl behenate was most effective at inhibiting the production of lactone, the acid degradation product of rosuvastatin. Therefore, the multilayer-coated tablet included a hydrophobic separation layer consisting of glyceryl behenate between the clopidogrel core tablet and the rosuvastatin coating layer. In order to prevent delayed dissolution by the stable hydrophobic separation layer, crospovidone was added into the clopidogrel core tablet as an effective disintegrant. Copovidone was also added to the coating layer of rosuvastatin, achieving a dissolution profile comparable to that of the reference drug, Crestor®. The resulting multilayer-coated tablet exhibited similar pharmacokinetic profiles to those of reference drugs (Plavix® and Crestor®) in beagle dogs, and there was no statistically significant difference in the maximum plasma concentration (Cmax), the time to reach the maximum plasma concentration (Tmax), or the area under the plasma-concentration time curve (AUC) between the test and reference formulations. The storage stability tests showed that the amounts of acid degradation products and total impurities were comparable to that of the reference drug. In conclusion, the present study successfully developed a stable multilayer-coated tablet containing both clopidogrel and rosuvastatin that may improve the patient compliance in combination therapy for cardiovascular diseases.
- Influence Of Composition On The Thermal Behavior Of Oils Extracted From The Seeds Of Some Romanian Grapes. [Journal Article]
- JSJ Sci Food Agric 2019 Jul 01
- CONCLUSIONS: Compared to pure samples of glyceryl-unsaturated fatty acids (glyceryl-trioleate, glyceryl-trilinoleate), the grape seed oils exhibit higher thermal stability, due to the presence of antioxidant compounds and to a synergistic action of unsaturated and saturated fatty acids, smaller percentage of the polyunsaturated and higher percentage of the saturated fatty acids enhancing the stability. This article is protected by copyright. All rights reserved.
- Characterization of the composition and the techno-functional properties of mannoproteins from Saccharomyces cerevisiae yeast cell walls. [Journal Article]
- FCFood Chem 2019 Nov 01; 297:124867
- Broad molecular weight (MW) distribution and variability of mannan to protein ratio of purified mannoproteins (MP), isolated from yeast cell walls upon the enzymatic treatment, revealed their multipl…
Broad molecular weight (MW) distribution and variability of mannan to protein ratio of purified mannoproteins (MP), isolated from yeast cell walls upon the enzymatic treatment, revealed their multiplicity. The main fraction of high-MW Agrimos®-MP1 and YCW-b-MP1' contained mannoproteins with a mannan to protein ratio of 3.5 and 6.9, respectively. Low-MW YCW-b-MP2' was mainly comprised of mannan, with a ratio of 181, whereas low-MW Agrimos®-MP2 was characterized by a ratio of 12.2. The solubility of MP1/MP2 was higher than that of MP1'/MP2'. Mannoproteins showed similar or lower solubility than mannan, and they exhibited a Newtonian behaviour. Sonication was the appropriate method for the formation of mannoproteins-based emulsions. Contrary to MP1/MP1'-based emulsions, MP2/MP2'-based ones showed higher affinity towards soybean oil than glyceryl-trioleate. pH affected the emulsifying ability of MP1/MP1'. MP1/MP1' showed similar or slightly inferior emulsifying properties than lecithin. This study is expected to broaden the applications of mannoproteins as value-added ingredients.
- Associations between change in blood pressure and functional outcome, early events and death: results from the Efficacy of Nitric Oxide in Stroke trial. [Journal Article]
- JHJ Hypertens 2019 Jul 01
- CONCLUSIONS: Modest decreases in SBP in acute stroke appear to be associated with fewer early events and better long-term functional outcome.
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- Multicentre Randomised trial of Acute Stroke treatment in the Ambulance with a nitroglycerin Patch (MR ASAP): study protocol for a randomised controlled trial. [Journal Article]
- TTrials 2019 Jun 26; 20(1):383
- CONCLUSIONS: MR ASAP will assess whether very early administration of GTN improves outcome after stroke in a setting where rates of intravenous thrombolysis and endovascular treatment for acute ischaemic stroke are high. The deferred consent procedure facilitates prompt GTN treatment and will prevent delay to revascularisation therapies. If early transdermal GTN treatment proves to be effective, this low-cost treatment can be readily implemented into daily clinical practice.