Acid Succinate Research Articles

Role of Magnetic Resonance Spectroscopy in the Evaluation of Ring Enhancing Lesions of the Brain

Introduction: The ring enhancing lesions of the brain are a challenging group of lesions with the variable possibilities of diagnosis under conventional Magnetic Resonance Imaging (MRI). Employing advanced techniques such as Magnetic Resonance Spectroscopy (MRS) could increase the success rates of the diagnosis. Aim: To assess the role of MRS in evaluating varying ring enhancing lesions of the brain. Materials and Methods: This prospective observational study involved 50 patients aged between 3-82 years who were detected with ring enhancing lesions of the brain on contrast MR studies. The patients underwent MRS evaluation. Categorical data was represented as frequency (%). The metabolite peaks of choline, lipid, lactate, N-Acetyl Aspartate (NAA), succinate and amino acids were recorded. The choline/creatine ratio was calculated and associated with the type of lesion the patients exhibited. Results: Among the 50 patients screened, the most prevalent pathologies were tuberculoma (36%) and neurocysticercosis (22%). While the patients diagnosed with tuberculoma presented with higher peak level of lipids and choline/creatine ratio of >1-2. Increased lactate, succinate, choline peak concomitant with no or insignificant lipid peak, were noted in the cases of neurocysticercosis. Primary brain tumour showed high choline peaks and elevated choline/creatine ratio (>2). Metastasis showed increased choline peak. Cerebral abscess showed increased amino acids and lactate peak. Conclusion: The diagnosis of varying ring enhancing lesions of the brain was accurately investigated by MRS. This accuracy enables delineating a treatment plan void of any dilemma.

Identifying novel metabolite biomarkers of adherence to a cluster analysis-derived healthy dietary pattern

AbstractThe MEDDINI intervention study investigated how advice improved the adoption of a Mediterranean diet (MD) in cardiovascular disease patients. Earlier research profiled the levels of blood metabolites in MEDDINI participants, in the process discovering a number dietary biomarkers indicative of a MD. However, a potential limitation of this approach is that MD scores are semi-quantitative, and don't reflect the absolute amounts of food consumed. Therefore, the present study identified distinct dietary patterns based on quantified food diary data from 58 MEDDINI participants by applying k-means clustering analysis. Previously measured blood metabolites (90) using targeted and untargeted methods were then assessed for their performance as dietary biomarkers. After careful standardisation (z-scores), optimisation and cross-validation dietary data were reduced to 6 specific food groups and this led to the formation of two clusters. Cluster 1 included participants who had the lowest intakes of fruit and vegetables, legumes, fish and whole grain cereals and the highest intake of meat and sweet foods (including carbonated drinks). Cluster 2 comprised the participants with highest intake of fruit and vegetables, legumes, fish and whole grain cereals and the lowest intake of meat and sweet foods (including carbonated drinks). Discriminatory metabolites (p derived from untargeted analysis included Citric acid, Tyrosine, Malonate, Pyroglutamic acid, Succinate, Betaine, L-asparagine and Fumaric acid which were significantly increased in cluster 2, and 2-Hydroxybutyric acid and Pyruvic acid which were significantly decreased in cluster 2. Targeted biomarker analysis showed 8 discriminatory metabolites which were significantly (p increased in cluster 2. These were Docosahexaenoic acid (DHA), alpha-Carotene, beta-Carotene, beta-Cryptoxanthin, Vitamin C, Lutein, alpha-Linolenic acid and Lycopene. Conversely Osbond acid, Cholesterol and Dihomo-γ-linolenic acid (DGLA) were significantly lower in cluster 2. Metabolites significantly correlated with some of the 6 groups in the clusters. For example, Citric acid, Betaine and Vitamin C positively correlated with combined fruit, fruit juice and vegetable intake: (r = 0.20, p = 0.018; r = 0.20, p = 0.02 and r = 0.34, p = 5.7E-5 respectively). DHA, alpha-Carotenoid and beta-Carotenoid significantly correlated with fish intake (r = 0.58, p = 1.94E-13; r = 0.40, p = 2E-6 and r = 0.30, p = 3.5E-4 respectively). The present study demonstrates the utility of clustering analysis for effectively assessing adherence to healthy dietary patterns and the discovery of novel dietary biomarkers.

Metabolic Regulation and Development of Energy Cane Setts upon Auxin Stimulus.

Energy cane is a bioenergy crop with an outstanding ability to bud sprouting and increasing yield in ratoon cycles even in marginal lands. Bud fate control is key to biomass production and crop profits due to vegetative propagation and tiller dependency, as well as phenotype plasticity to withstand harsh environmental conditions. During the establishment stage (plant cane cycle), energy cane has a tendency for low root:shoot ratio, which might hamper the ability to cope with stress. Auxin is known to modulate bud sprouting and stimulate rooting in sugarcane. Hence, we treated a slow and a fast bud sprouting energy cane cultivars with auxin or controls (with and without water soaking) for 6 h prior to planting and evaluate plant growth parameters and metabolic profiling using two techniques (gas chromatography with time-of-flight mass spectrometer and nuclear magnetic resonance) to characterize the effect and identify metabolite markers associated with bud inhibition and outgrowth. Auxin inhibited bud burst and promote rooting in setts changing the root:shoot ratio of plantlets. Metabolome allowed the identification of lactate, succinate and aspartate family amino acids as involved in bud fate control through the potential modulation of oxygen and energy status. Investigating environmental and biochemical factors that regulate bud fate can be incremental to other monocot species. Our study provides new insights into bud quiescence and outgrowth in cane hybrids, with the potential to leverage our understanding of yield-related traits, crop establishment and adaptation to global climate change.

Effects of Pyruvic Acid, Succinic Acid, and Oregano Essential Oil on Salmonella, Natural Microflora, and Quality of Raw Ground Chicken

ObjectivesThe growing stringency of regulations related to pathogens in raw poultry and increasing consumer demand for more natural food ingredients makes it imperative to explore alternative antimicrobial agents. The aim of this study was to assess the anti-Salmonella effect of combinations of succinate or pyruvic acid with oregano essential oil in raw ground chicken. Additionally, their effect on natural microflora and quality of ground chicken over simulated retail display was evaluated.Materials and MethodsNalidixic acid (NA) adapted Salmonella Typhimurium was inoculated on skin-on broiler breast meat pieces. The antimicrobial treatments given to meat were 2 and 3% pyruvic acid (PA) or monosodium succinate (SA) in combination with 0.5% essential oil (EO). Agar at the concentration of 0.05% was added to water used to prepare antimicrobial solutions to disperse the essential oil. Mode of antimicrobial treatment was 30 s dip. The meat was then ground and evaluated for pathogen reduction. Data were analyzed using 1-way ANOVA. Surviving Salmonella were recovered on XLT-4 with 50 ppm NA. Non-inoculated meat was similarly treated with antimicrobial dip and ground. Ground chicken was packaged in foam trays with PVC overwrap, and evaluated for mesophilic aerobic plate count (APC), psychrotrophic count (PC), pH, instrumental color (CIE L*, a*, and b*), and expressible moisture over 8 d of simulated retail display.A factorial design was assigned to the experiment with antimicrobial treatments and display days as the fixed effect factors. Data were analyzed using a mixed general linear model that considered replicates as a random effect in addition to the mentioned fixed effects. All trials were conducted in three replicates.ResultsMaximum reduction obtained in Salmonella counts from ground chicken was 1.52 log CFU/g and 0.98 log CFU/g, resulting from 3% SA + 0.5% EO, and 3% PA + 0.5% EO, respectively. Three percent SA + 0.5% EO treatment resulted in ground chicken with approximately 1.2 log CFU/g lower APC on Day 8 that was significantly lower (P < 0.05) than all other treatments. This treatment also resulted in less pH variation over the entire shelf life duration and lighter color of ground meat on Day 8.ConclusionThese results indicate that combination of monosodium succinate and oregano essential oil provides effective reduction of Salmonella and improved raw quality of ground chicken. This antimicrobial combination can be employed as a clean label ingredient for raw chicken applications.

Accelerated biodegradation testing of slowly degradable polyesters in soil

According to the impending EU regulations, all polymer products used in agriculture and applied into soil must be biodegradable to prevent their accumulation in the environment. However, some of these products must serve their purpose for months up to years before their degradation and mineralization is desirable. Current international standards describing the biodegradability in soil are more directed towards materials that undergo relatively fast biodegradation, which hampers the development and certification of slowly biodegrading polymeric materials. Here, an accelerated soil biodegradation test is proposed, where by increasing the incubation temperature from 25 °C to 37 °C, up to about 4-fold increase in the biodegradation rate is achieved. The polymers tested include TÜV AUSTRIA Belgium certified polyhydroxyalkanoate (PHA), polybutylene succinate (PBS), polybutylene adipate-terephthalate and polylactic acid blend (PBAT/PLA) and an experimental polyester network (ICL-PN). The biodegradation rates of the given polymers at the two temperatures was examined by carbon dioxide evolution. Independent testing was done in two independent laboratories and the results were compared. The biodegradation of the materials was further assessed by electron microscopy and the microbial community present was analyzed by next-generation sequencing. Criteria were proposed for the accelerated test method, which include that the polymers eligible for the accelerated test should not manifest any phase transition, like e.g. a glass transition, in the interval from 25 °C to 37 °C. The proposed accelerated test can be helpful in the development of polymeric materials with a functional life of several years and with ultimately quantitative biodegradability.

Characterization and Metabolism Effect of Seed Endophytic Bacteria Associated With Peanut Grown in South China.

Endophytes are considered to be excellent biocontrol agents and biofertilizers, and are associated with plant growth promotion and health. In particular, seed-endophytic bacteria benefit the host plant’s progeny via vertical transmission, and can play a role in plant growth and defense. However, seed-associated endophytic bacteria have not been fully explored, with very little known about how they interact with peanut (Arachis hypogaea), for example. Here, 10 genera of endophytic bacteria were isolated from the root tips of peanut seedlings grown either aseptically or in soil. Forty-two bacterial colonies were obtained from peanut seedlings grown in soil, mostly from the genus Bacillus. Eight colonies were obtained from aseptic seedling root tips, including Bacillus sp., Paenibacillus sp., and Pantoea dispersa. Four Bacillus peanut strains GL1–GL4 (B.p.GL1-GL4) produced bio-films, while B.p.GL2 and Paenibacillus glycanilyticus YMR3 (P.g.YMR3) showed strong amylolytic capability, enhanced peanut biomass, and increased numbers of root nodules. Conversely, P. dispersa YMR1 (P.d.YMR1) caused peanut plants to wilt. P.g.YMR3 was distributed mainly around or inside vacuoles and was transmitted to the next generation through gynophores and ovules. Hexanoate, succinate, and jasmonic acid (JA) accumulated in peanut root tips after incubation with P.g.YMR3, but linolenate content decreased dramatically. This suggests that strain P.g.YMR3 increases JA content (14.93-fold change) and modulates the metabolism of peanut to facilitate nodule formation and growth. These findings provide new insight into plant–seed endophytic bacterial interactions in peanut.

КОМПЛЕКСНЕ ЛІКУВАННЯ СИНДРОМУ ДІАБЕТИЧНОЇ СТОПИ

The aim was to develop a comprehensive treatment of DFS, using reconstructive surgeries and indirect revascularization methods. Our work is based on 25 year experience of treatment of 1107 patients with DFS, who were treated in Ivano-Frankivsk Central hospital. Patients were examined on admission: common clinical methods, angiography, densitometry, electronic microscopy and histochemical examination of limb tissues, TcpO2 and regional cytokine reaction. Results showed that reconstructive operations on limb arteries, in case if it was possible, were the best method of treatment. Indications for surgery were TcpO2≤25 mm.hd. Mekenberg sclerosis III was contraindication for reconstructive surgery. Tissue vitality, its future regeneration possibility depends on succinate dehydrogenase and acid phosphatase. In vital mussels of the hip, shin and foot succinate dehydrogenase range was 3-5 points, in dead tissues- 0. Acid phosphatase in vital 0-1 points, in dead tissues- 4-5. Surgical tactic algorithm was developed ccording to electronic microscopy and histochemistry. It was based on tissue vitality and gave us an answer to what part of limb must be amputated. Indication for amputation was high level of acid phosphatase, bone tissue destruction, massive purulent destructions of soft tissues, gangrene. Bone trepanation causes decreasing of internal bone tissue, decreasing of intraossal receptor irritation, increases local microcirculation. For elimination of myelodepresion and erythropoiesis stimulation we offered intraspongious automyelotransplantation which caused to extra anatomical connection’s between intraossal and muscular neoangiogenesis. Topical treatment of trophic ulcers was performed by auto desmoplastic and cultures of fibroblasts which can cover defect as by themselves and as causes to better skin autotransplant healing. We get a positive effect of prolonged intraarterial antibiotic therapy with erytrocytal containers which make antibiotic exposition in infection localization up to 36 hours.

COMPREHENSIVE TREATMENT OF DIABETIC FOOT SYNDROME

The aim was to develop a comprehensive treatment of DFS, using reconstructive surgeries and indirect revascularization methods. Our work is based on 25 year experience of treatment of 1107 patients with DFS, who were treated in Ivano-Frankivsk Central hospital. Patients were examined on admission: common clinical methods, angiography, densitometry, electronic microscopy and histochemical examination of limb tissues, TcpO2 and regional cytokine reaction. Results showed that reconstructive operations on limb arteries, in case if it was possible, were the best method of treatment. Indications for surgery were TcpO2≤25 mm.hd. Mekenberg sclerosis III was contraindication for reconstructive surgery. Tissue vitality, its future regeneration possibility depends on succinate dehydrogenase and acid phosphatase. In vital mussels of the hip, shin and foot succinate dehydrogenase range was 3-5 points, in dead tissues- 0. Acid phosphatase in vital 0-1 points, in dead tissues- 4-5. Surgical tactic algorithm was developed ccording to electronic microscopy and histochemistry. It was based on tissue vitality and gave us an answer to what part of limb must be amputated. Indication for amputation was high level of acid phosphatase, bone tissue destruction, massive purulent destructions of soft tissues, gangrene. Bone trepanation causes decreasing of internal bone tissue, decreasing of intraossal receptor irritation, increases local microcirculation. For elimination of myelodepresion and erythropoiesis stimulation we offered intraspongious automyelotransplantation which caused to extra anatomical connection’s between intraossal and muscular neoangiogenesis. Topical treatment of trophic ulcers was performed by auto desmoplastic and cultures of fibroblasts which can cover defect as by themselves and as causes to better skin autotransplant healing. We get a positive effect of prolonged intraarterial antibiotic therapy with erytrocytal containers which make antibiotic exposition in infection localization up to 36 hours.

Succinate receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Nomenclature as recommended by NC-IUPHAR [7]. The Succinate receptor has been identified as being activated by physiological levels of the Kreb's cycle intermediate succinate and other dicarboxylic acids such as maleate in 2004. Since its pairing with its endogenous ligand, the receptor has been the focus of intensive research and its role has been evidenced in various (patho)physiological processes such as regulation of renin production, retinal angiogenesis, inflammation or immune response.

Biodegradable reduction-responsive polymeric micelles for enhanced delivery of melphalan to retinoblastoma cells

Melphalan (MEL) is an effective chemotherapeutic agent for treatment of retinoblastoma (Rb) which is the most common childhood malignancy. However, the inherent cardiopulmonary toxicity and hazardous integration limit its therapeutic effect on RB. N-Acetylheparosan (AH), a natural heparin-like polysaccharide in mammals with long circulation effect and good biocompatibility, was linked by d-α-tocopherol acid succinate (VES) via and cystamine (CYS) to synthesize reduction-responsive N-acetylheparosan-CYS-Vitamin E succinate (AHV) copolymers. In addition, CYS was replaced by adipic acid dihydrazide (ADH) to obtain a control of non-reduction-responsive polymers N-acetylheparosan-ADH-Vitamin E succinate (ADV). MEL-loaded AHV micelles (MEL/AHV) as well as ADV micelles (MEL/ADV) were prepared with small particle size and high drug loading content. In vitro drug release showed that MEL/AHV micelles presented obvious reduction-triggered release behavior compared with MEL/ADV. In vitro antitumor effects were investigated using WERI-Rb-1 retinoblastoma cells. Cytotoxicity experiments showed that the IC50 of MEL/AHV was significantly lower than that of free MEL and MEL/ADV, suggesting that MEL/AHV enhanced the cytotoxicity against retinoblastoma cells. Furthermore, MEL/AHV micelles were more easily uptaken by multiple pathways compared with MEL/ADV and free MEL. Therefore, MEL/AHV might be a potential delivery system for enhanced delivery of melphalan to Rb cells.

Multi-Drug Induced Palmar and Plantar Lichen Planus: First Description in the Medical Literature!

In consultation with a cardiologist it was decided to stop rosuvastatin, ramipril, metoprolol succinate and acetylsalicylic acid, and in replacement the patient started lercanidipine 10 mg bid, clopidogrel 75 mg id and ivabradine.

Differential metabolic responses of shrubs and grasses to water additions in arid karst region, southwestern China

Increasing precipitation has been predicted to occur in the karst areas in southwestern regions of China. However, it is little known how various plants respond to increasing precipitation in this region. Here we determined the impacts of water addition on leaf metabolites of grasses (Cymbopogon distans and Arundinella sitosa) and shrubs (Carissa spinarum and Bauhinia brachycarpa) in this area. Four levels of water additions (CK, T1, T2 and T3 indicating 0%, +20%, +40% and +60% relative to the current monthly precipitation, respectively) were designed. Sphingolipids substantially increased in the leaves of all four species with increasing water supply which suggests that these plants adopted biochemical strategy to tolerate the wet stress. However, both shrubs showed decreases in valine and threonine (amino acids), threonate, succinate and ascorbic acid (organic acids), galactose and rhamnose (sugars) and epicatchin and oleamides (secondary metabolites) with increasing water supply. Both grasses increased in the total metabolites at T1, but the total metabolites in A. sitosa significantly decreased at T2 and T3 while remains unchanged in C. distans. Tri-carboxylic acid cycle and amino acid metabolism in shrubs and shikimate pathway in grasses were strongly affected with water supply. Overall, shrubs and grasses respond differentially to variation in water addition in terms of metabolomics, which is helpful in understanding how plants respond to climate change.

Amorphous solid dispersions of weak bases with pH-dependent soluble polymers to overcome limited bioavailability due to gastric pH variability – An in-vitro approach

Several drugs are pH-dependent soluble weak bases with a poor solubility in the intestinal pH range. Additionally a variable gastric pH, which is a common issue in the population, potentially reduces the in-vivo performance due to reduced solubility at elevated pH. Aiming to avoid the influence of variable gastric pH on the dissolution performance, enteric polymers – hydroxypropylmethylcellulose acetate succinate (HPMCAS), hydroxypropylmethylcellulose phthalate (HP-55, HP-50) and methacrylic acid ethylacrylate copolymer (Eudragit L100-55) together with nevirapine as model drug were used for the preparation of solid dispersions by hot-melt extrusion. We were able to generate solid dispersions without crystalline residuals. The resulting solid dispersions were further tested for stability and dissolution performance applying two different pH-shift experiments (non-sink conditions), to simulate standard and altered gastric conditions. Solid dispersions made of enteric polymers were independent to gastric pH variability and exhibited superior dissolution performances compared to their respective physical mixtures and neat nevirapine.

MORPHOLOGIC SPECIFICITIES OF HEPATOPROTECTIVE EFFECTS OF ANTIHYPOXANTS IN EXPERIMENTAL ACUTE LIVER DAMAGE WITH CARBON TETRACHLORIDE

The article presents the results on liver morphologic changes in acute carbon tetrachloride damage and its preventive correction by antihypoxants: complex oxymethyluracil agents (with sodium succinate and ascorbic acid). It has been shown that carbon tetrachloride causes pronounced morphologic changes in the liver and preventive use of the antihypoxants studied decreases intensity and prevalence of dystrophic processes in liver tissues. The analysis of comparative efficiency of the agents studied has been carried out.

Parabacteroides distasonis Alleviates Obesity and Metabolic Dysfunctions via Production of Succinate and Secondary Bile Acids

We demonstrated the metabolic benefits of Parabacteroides distasonis (PD) on decreasing weight gain, hyperglycemia, and hepatic steatosis in ob/ob and high-fat diet (HFD)-fed mice. Treatment with live P.distasonis (LPD) dramatically altered the bile acid profile with elevated lithocholic acid (LCA) and ursodeoxycholic acid (UDCA) and increased the level of succinate in the gut. Invitro cultivation of PD demonstrated its capacity to transform bile acids and production of succinate. Succinate supplementation in the diet decreased hyperglycemia in ob/ob mice via the activation ofintestinal gluconeogenesis (IGN). Gavage with a mixture of LCA and UDCA reduced hyperlipidemia by activating the FXR pathway and repairing gutbarrier integrity. Co-treatment with succinate and LCA/UDCA mirrored the benefits of LPD. The binding target of succinate was identified as fructose-1,6-bisphosphatase, the rate-limiting enzyme in IGN. The succinate and secondary bile acids produced by P.distasonis played key roles in the modulation of host metabolism.

Porous Electrospun Nanofiber from Biomass-Based Polyester Blends of Polylactic Acid and Polybutylene Succinate

We studied the electrospinning process of the blend of polylactic acid (PLA) and polybutylene succinate (PBS). The blend PLA/PBS ratio 95/5, 90/10, 85/15 and 80/20 wt% were prepared by dissolved in mixture of solvent between dichloromethane (DCM) and N, N-dimethylformamide (DMF) at ratio 3/1. The suitable condition for electrospun of the blend was 17% wt concentration, 16 kV and 18 cm projection distance. The round fiber with pore on the surface was observed. Increasing content of PBS in the blend impact to the diameter of fibril decreased from 1350, 1290, 1210 and 1170 nm, respectively; while the pore on the surface changes from circle to oval shape. Regarding the thermal properties, blending of PBS increases the glass transition temperature (Tg) of PLA without affect to the melting temperature (Tm) of the electrospun nanofibers. The best tensile properties of PLA/PBS nanofibers were achieved at blend ratio of 95/5, and Young’s modulus is increased comparing to those of the pure electrospun fibers.

Dual-functionalized liposome by co-delivery of paclitaxel with sorafenib for synergistic antitumor efficacy and reversion of multidrug resistance

Multidrug resistance (MDR) remains one of the major reasons for inefficiency of many chemotherapeutic agents in cancer therapy. In this study, a D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and polylysine-deoxycholic acid copolymer (PLL-DA) co-modified cationic liposome coating with hyaluronic acid (HA) was constructed for co-delivery of paclitaxel (PTX) and chemosensitizing agent, sorafenib (SOR) to treat the MDR cancer. The multifunctional liposome (HA-TPD-CL-PTX/SOR) presented good stability against rat plasma and was capable of reversing surface zeta potential under acidic conditions in the presence of HAase. Additionally, experimental result confirmed that the PLL-DA copolymer would facilitate the endo-lysosomal escape of the liposome. In vitro study demonstrated that HA-TPD-CL-PTX/SOR could significantly enhance drug accumulation in resistant MCF-7/MDR cells by inhibiting the P-gp efflux, and effectively inhibited growth of tumor cells. Furthermore, the liposome showed an enhanced anticancer activity in vivo, with a tumor growth inhibition rate of 78.52%. In summary, HA-TPD-CL-PTX/SOR exhibited a great potential for effective therapy of resistant cancers by combining with chemotherapeutic agents and could be a promising nano-carrier for reversing MDR and improving the effectiveness of chemotherapy.

Effect of the extent of ethanol removal on the volatile compounds of a Chardonnay wine dealcoholized by vacuum distillation

“Beverages obtained from the partial dealcoholization of wine” are those drinks whose final alcoholic degree after dealcoholization is lower than that of a wine and higher than or equal to 0.5% v/v. When the total alcoholic degree is lower than 0.5% v/v the denomination is “Beverages obtained from the dealcoholization of wine”. The practices to be authorized for the production of these drinks with the dealcoholized wine fractions are currently being studied at OIV. The characterization of the composition of these fractions is essential to identify the necessary corrective practices. The present work was aimed at monitoring the losses of the main volatile compounds of a Chardonnay wine with the proceeding of the dealcoholization process by vacuum distillation. The wine was subjected to total dealcoholization, and during the process the evaporated fractions, re-condensed at 9 ∘C, were collected in aliquots of 1.25 L each. The ethanol content of each fraction was measured, and for the first 20 fractions the content in volatile compounds was determined with GC-MS. The results show that the losses of volatile compounds during the dealcoholization process follow different trends depending on the molecules considered. The most volatile compounds, generally with the lowest perception thresholds, were mainly present in the first evaporated fractions. The greatest losses concerned isoamylacetate, ethyl hexanoate and ethyl octanoate. Conversely, a greater number of molecules were present at similar concentrations in the different fractions, and their losses followed a linear or sometimes exponential trend: in particular, these compounds included n-hexanol, 2-phenylethanol, diethyl succinate and medium chain fatty acids (hexanoic, octanoic and decanoic acids). In the wine dealcoholized at 3.36% v/v (loss of ethanol equal to 7.43% v/v, corresponding to the 20th and last recondensed fraction), some volatile compounds were no longer detectable or quantifiable; in particular, these compounds were isoamylacetate, ethylhexanoate, hexylacetate, n-hexanol and other alcohols with 6 carbon atoms and ethyl octanoate. Other compounds, such as hexanoic, octanoic and decanoic acids, and, in particolar, β-phenylethanol, benzylic aalcohol and γ-butyrolactone, underwent lower percentage losses than those of ethanol. The dealcoholization process can therefore deeply modify the original aromatic profile of the wines, intervening on the absolute concentration and on the relative ratios of the single molecules.

Optimized vinpocetine-loaded vitamin E D-α-tocopherol polyethylene glycol 1000 succinate-alpha lipoic acid micelles as a potential transdermal drug delivery system: in vitro and ex vivo studies.

BackgroundVinpocetine (VNP), a semisynthetic natural product, is used as a vasodilator for cerebrovascular and age-related memory disorders. VNP suffers from low oral bioavailability owing to its low water solubility and extensive first-pass metabolism. This work aimed at utilizing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and alpha lipoic acid (ALA) to develop efficient micellar system for transdermal delivery of VNP.Materials and methodsVNP-TPGS-ALA micelles were prepared, characterized for particle size using particle size analyzer, and investigated for structure using transmission electron microscope. Optimization of VNP-TPGS-ALA micelles-loaded transdermal films was performed using Box–Behnken experimental design. The investigated factors were percentage of ALA in TPGS (X1), citral concentration (X2), and propylene glycol concentration (X3). Elongation percent (Y1), initial permeation after 2 hours (Y2), and cumulative permeation after 24 hours (Y3) were studied as responses.ResultsStatistical analysis revealed optimum levels of 16.62%, 3%, and 2.18% for X1, X2, and X3, respectively. Fluorescent laser microscopic visualization of skin penetration of the optimized transdermal film revealed marked widespread fluorescence intensity in skin tissue after 0.5, 2, and 4 hours compared with raw VNP transdermal film formulation, which indicated enhancement of VNP skin penetration.ConclusionThe obtained results highlighted the potentiality of VNP nanostructure-based films for controlling the transdermal permeation of the drug and improving its effectiveness.

Naftopidil-fumaric acid interaction in a solid dispersion system: Improving the dissolution rate and oral absorption of naftopidil in rats

The aim of this study was to improve the dissolution rate and oral absorption of naftopidil (NAF) in rats via solid dispersion (SD) with a weak acid and copolymer. We hypothesized that the dissolution rate and oral bioavailability of NAF would increase through hydrogen bonding between NAF and weak acids/hydrophilic polymers. d‑α‑Tocopherol polyethylene glycol 1000 succinate (TPGS) and fumaric acid were selected as the hydrophilic polymer and weak acid based on their apparent solubility and pre-dissolution test results, respectively. The optimal formulation (SD5) comprised NAF: fumaric acid: TPGS: Aerosil® 200 at a ratio of 1:1:1:1. The dissolution rate of SD5 in distilled water and pH 1.2 media was significantly higher than that of a commercial product (Flivas®). The chemical interaction between NAF and fumaric acid was confirmed using attenuated total reflectance Fourier transform infrared spectroscopy. The SD5 formulation was stable for 12 months. The oral bioavailability and peak plasma concentration (Cmax) of NAF present in the SD5 formulation improved compared with those of Flivas® after oral administration to rats (185% and 1.88-fold, respectively). In conclusion, fumaric acid is the major factor contributing to the TPGS-induced improvement of the dissolution rate of NAF in SD5 formulation, thereby increasing the oral absorption of NAF in rats.