Computational Study on the Inhibition Mechanisms of the Ziegler-Natta Catalyst in the Propylene Polymerization Process: Part 1 Effects of Acetylene and Methylacetylene.

Acetylene and methylacetylene are impurities commonly found in the raw materials used for the production of polymers such as polypropylene and polyethylene. Experimental evidence indicates that both acetylene and methylacetylene can decrease the productivity of the Ziegler-Natta catalyst and alter the properties of the resulting polymer. However, there is still a lack of understanding regarding the mechanisms through which these substances affect this process. Therefore, elucidating these mechanisms is crucial to develop effective solutions to this problem. In this study, the inhibition mechanisms of the Ziegler-Natta catalyst by acetylene and methylacetylene are presented and compared with the incorporation of the first propylene monomer (chain initiation) to elucidate experimental effects. The Density Functional Theory (DFT) method was used, along with the B3LYP-D3 functional and the 6-311++G(d,p) basis set. The recorded adsorption energies were -11.10, -13.99, and -0.31 kcal mol-1, while the activation energies were 1.53, 2.83, and 28.36 kcal mol-1 for acetylene, methylacetylene, and propylene, respectively. The determined rate constants were 4.68 × 1011, 5.29 × 1011, and 2.3 × 10-8 M-1 s-1 for acetylene, methylacetylene, and propylene, respectively. Based on these values, it is concluded that inhibition reactions are more feasible than propylene insertion only if an ethylene molecule has not been previously adsorbed, as such an event reinforces propylene adsorption.

Propylene Glycol Potentiates the Inhibitory Action of CTZ Paste on Antibiotic-Resistant Enterococcus faecalis Isolated from the Root Canal: An In Vitro Study.

This study aimed to evaluate if the change of vehicle for CTZ (Chloramphenicol, Tetracycline, zinc oxide, and Eugenol) paste improves the inhibition of Enterococcus faecalis in vitro. The vehicles evaluated alone and mixed with CTZ were Eugenol, propylene glycol (PG), super-oxidized solution (SOS), grapefruit-seed extract (GSE), and 0.9% saline solution as a negative control. A clinical isolate of E. faecalis was morphologically and biochemically characterized, and its antimicrobial susceptibility was tested using 20 antimicrobial agents. Once characterized, the clinical isolate was cultivated to perform the Kirby-Bauer disc diffusion method with paper discs embedded with the different vehicles mixed or used alone, and incubated at 37 °C for 24 h. Data were analyzed using one-way ANOVA, and the means were compared using Tukey test with a significance level of p < 0.05. For vehicles used alone, GSE presented the greatest inhibition showing a statistically significant difference with the rest of the vehicles. When vehicles were mixed with the CTZ paste, PG showed a greater inhibition with a statistically significant difference from the rest of the vehicles. In conclusion, the vehicle used to mix the CTZ paste plays an important role in the inhibition of E. faecalis in vitro; therefore, we consider that this can be an important factor to achieve success in the use of this technique.

Heterogeneous Catalysts for Glycerol Biorefineries: Hydrogenolysis to 1,2-Propylene Glycol.

Research on the use of biomass resources for the generation of energy and chemical compounds is of great interest worldwide. The development and growth of the biodiesel industry has led to a parallel market for the supply of glycerol, its main by-product. Its wide availability and relatively low cost as a raw material make glycerol a basic component for obtaining various chemical products and allows for the development of a biorefinery around biodiesel plants, through the technological integration of different production processes. This work proposes a review of one of the reactions of interest in the biorefinery environment: the hydrogenolysis of glycerol to 1,2-propylene glycol. The article reviews more than 300 references, covering literature from about 20 years, focusing on the heterogeneous catalysts used for the production of glycol. In this sense, from about 175 catalysts, between bulk and supported ones, were revised and discussed critically, based on noble metals, such as Ru, Pt, Pd, and non-noble metals as Cu, Ni, Co, both in liquid (2-10 MPa, 120-260 °C) and vapor phase (0.1 MPa, 200-300 °C). Then, the effect of the main operational and decision variables, such as temperature, pressure, catalyst/glycerol mass ratio, space velocity, and H2 flow, are discussed, depending on the reactors employed. Finally, the formulation of several kinetic models and stability studies are presented, discussing the main deactivation mechanisms of the catalytic systems such as coking, leaching, and sintering, and the presence of impurities in the glycerol feed. It is expected that this work will serve as a tool for the development of more efficient catalytic materials and processes towards the future projection of glycerol biorefineries.

Prospective insight into the role of benzyl propylene glycoside as a modulator of the cGAS-STING signaling pathway in the management of nonalcoholic fatty pancreas animal model.

BACKGROUND: Nonalcoholic fatty pancreatitis (NAFP) is one of the metabolic syndrome manifestations that need further studies to determine its molecular determinants and find effective medications. We aimed to investigate the potential effect of benzyl propylene glycoside on NAFP management via targeting the pancreatic cGAS-STING pathway-related genes (DDX58, NFκB1 & CHUK) and their upstream regulator miRNA (miR-1976) that were retrieved from bioinformatics analysis. METHODS: The rats were fed either normal chow or a high-fat high-sucrose diet (HFHS), as a nutritional model for NAFP. After 8 weeks, the HFHS-fed rats were subdivided randomly into 4 groups; untreated HFHS group (NAFP model group) and three treated groups which received 3 doses of benzyl propylene glycoside (10, 20, and 30 mg/kg) daily for 4 weeks, parallel with HFHS feeding. RESULTS: The molecular analysis revealed that benzyl propylene glycoside could modulate the expression of the pancreatic cGAS-STING pathway-related through the downregulation of the expression of DDX58, NFκB1, and CHUK mRNAs and upregulation of miR-1976 expression. Moreover, the applied treatment reversed insulin resistance, inflammation, and fibrosis observed in the untreated NAFP group, as evidenced by improved lipid panel, decreased body weight and the serum level of lipase and amylase, reduced protein levels of NFκB1 and caspase-3 with a significant reduction in area % of collagen fibers in the pancreatic sections of treated animals. CONCLUSION: benzyl propylene glycoside showed a potential ability to attenuate NAFP development, inhibit pancreatic inflammation and fibrosis and reduce the pathological and metabolic disturbances monitored in the applied NAFP animal model. The detected effect was correlated with modulation of the expression of pancreatic (DDX58, NFκB1, and CHUK mRNAs and miR-1976) panel.

Ozone precursors and boundary layer meteorology before and during a severe ozone episode in Mexico city.

Volatile organic compounds (VOCs) data in conjunction with other inorganic pollutants, surface meteorological data and continuous measurement of the Planetary Boundary Layer height (PBLH) at an urban site in Mexico City were performed from 6 to 18 March 2016. Positive Matrix Factorization (PMF) identified four emission source factors of VOCs along with equivalent black carbon (eBC), gaseous pollutants (CO, NO, NO2, SO2, NH3) and ions (Na+, Mg2+, Ca2+, NO3-, NH4+): (1) secondary aerosol precursors, (2) evaporation and non-LPG fuel combustion, (3) geogenic source and (4) vehicle exhaust. Propylene Equivalent and Maximum Incremental Reactivity (MIR) methods identified isoprene and ethylene as the highest oxidant and O3 forming species. Pollutant data normalized to the variation of the PBLH revealed continued production of O3 precursors in the afternoon beyond the typical morning rush hour. In particular this could be observed during the second part of the measurement period (12-15 March) when a strong O3 episode occurred under weak wind and lower PBLH conditions compared to the preceding period (6-11 March) when well mixed conditions due to elevated daytime PBLH and strong advection led to overall reduced pollutant mixing ratios in the afternoon hours.

Prospective insight into the role of benzyl propylene glycoside as a modulator of the cGAS-STING signaling pathway in the management of nonalcoholic fatty pancreas animal model

BACKGROUND: Nonalcoholic fatty pancreatitis (NAFP) is one of the metabolic syndrome manifestations that need further studies to determine its molecular determinants and find effective medications. We aimed to investigate the potential effect of benzyl propylene glycoside on NAFP management via targeting the pancreatic cGAS-STING pathway-related genes (DDX58, NFκB1 & CHUK) and their upstream regulator miRNA (miR-1976) that were retrieved from bioinformatics analysis. METHODS: The rats were fed either normal chow or a high-fat high-sucrose diet (HFHS), as a nutritional model for NAFP. After 8 weeks, the HFHS-fed rats were subdivided randomly into 4 groups; untreated HFHS group (NAFP model group) and three treated groups which received 3 doses of benzyl propylene glycoside (10, 20, and 30 mg/kg) daily for 4 weeks, parallel with HFHS feeding. RESULTS: The molecular analysis revealed that benzyl propylene glycoside could modulate the expression of the pancreatic cGAS-STING pathway-related through the downregulation of the expression of DDX58, NFκB1, and CHUK mRNAs and upregulation of miR-1976 expression. Moreover, the applied treatment reversed insulin resistance, inflammation, and fibrosis observed in the untreated NAFP group, as evidenced by improved lipid panel, decreased body weight and the serum level of lipase and amylase, reduced protein levels of NFκB1 and caspase-3 with a significant reduction in area % of collagen fibers in the pancreatic sections of treated animals. CONCLUSION: benzyl propylene glycoside showed a potential ability to attenuate NAFP development, inhibit pancreatic inflammation and fibrosis and reduce the pathological and metabolic disturbances monitored in the applied NAFP animal model. The detected effect was correlated with modulation of the expression of pancreatic (DDX58, NFκB1, and CHUK mRNAs and miR-1976) panel.

Reducing chilling injury in 'Palmer' mangoes submitted to quarantine cold treatment.

BACKGROUND: Treatment with low temperatures can be used to quarantine mangoes against fruit-fly infestation. However, mangoes can develop chilling injury (CI) when stored at temperatures below 13 °C. We demonstrated that the immersion in polyol solutions can alleviate CI symptoms in 'Palmer' mangoes stored at 8 °C. These suggest that polyols can be used to reduce CI in mangoes during quarantine at low temperatures. Thus, we investigated the efficacy of applying 0.1% (v/v) glycerol, propylene glycol, or sorbitol to 'Palmer' mangoes subjected to cold treatment (1.0 °C) for 28 days. Mangoes were then ripened at 23 °C for 7 days. RESULTS: Among these polyols, sorbitol was the most effective in alleviating CI for up to 14 days of cold treatment. Mangoes treated with sorbitol showed lower levels of malondialdehyde (MDA) and hydrogen peroxide (H2 O2 ), and reduced polyphenol oxidase (PPO) activity. These fruit also had elevated levels of ascorbate (AsA), especially in the epicarp, and increased superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX) activity. CONCLUSION: Sorbitol can reduce the CI, but to an unsatisfying level, and it should be combined with other treatments storage at low temperature. © 2022 Society of Chemical Industry.

Natural Aging of Ethylene-Propylene-Diene Rubber under Actual Operation Conditions of Electrical Submersible Pump Cables.

Ethylene-propylene-diene monomer (EPDM) rubbers used in electric submersible pump (ESP) cables were analyzed after being aged in actual operation conditions in oil wellbores. These rubbers constitute the insulation and jacket layers of the ESP cables. EPDM rubbers from four different cables operating during different time intervals (2 and 4.8 years) at different depths (from 760 to 2170 m) below sea level were studied. To verify the effects of the long exposure on the rubber performance, thermal analysis was performed to determine the thermal stability and activation energy of degradation. In addition, structural analysis, through vibrational spectroscopy and crosslinking fraction assessment, was carried out. The mechanical properties of the aged rubbers were inferred through the measurement of hardness, while the absorption of a service fluid was studied by gravimetry. The results showed only minor changes in the thermal, structural, mechanical and barrier properties of the EPDM-based ESP cable layers. It is suggested that the thermo-oxidation mechanism followed by chain scission does not have a role in the degradation of EPDM within the aged ESP cables, and no sign of variation of crosslink fractions has been encountered. Therefore, it was concluded that EPDM-based layers seem not to be weak links in the configuration of modern ESP systems.

Plasticizer types and whey protein coatings on internal quality and shelf life of eggs stored for 42 days

Effects of plasticizer types and whey protein concentrate (WPC) as coatings were evaluated on internal quality and shelf life of eggs stored for 42 days. Eggs were coated with WPC at 8 % solution combined with the plasticizers glycerol (GLY), sorbitol (SOR), and propylene glycol (PRO). The eggs were stored at 20 °C. Weight loss, Haugh Unit (HU), albumen and yolk pH, and yolk index (YI) were evaluated weekly from day 0 to 42 days. After, electron microscopy of the eggshell structure was performed. The data was submitted to the analysis of variance and the effects of treatment, storage time, and the interaction between these factors were evaluated. There was significant interaction between factors (treatment and periods) for weight loss (p < 0.0001), HU (p < 0.0001), albumen (p < 0.0001), and yolk pH (p < 0.0001), and YI (p < 0.0001). After 42 days, uncoated eggs showed greater weight loss (5.4 %), compared to WPC+GLY, (3.8 %), WPC+SOR (3.3 %) and WPC+PRO (3.9 %). Similar results were verified for HU at 42 days of storage. Uncoated eggs showed HU of 58.46 (B), while coated eggs showed higher values: WPC+GLY 66.58 (A), WPC+SOR 68.79 (A), and WPC + PRO 71.53 (A). The plasticizers GLY, SOR and PRO, associated with WPC, demonstrated effectiveness in maintaining the quality of eggs throughout the 42 days of storage. However, WPC+SOR showed superiority in preserving quality integrity of eggs. This result can be related to the chemical structure of SOR, making the combination more efficient for storage.(AU)

Plasticizer types and whey protein coatings on internal quality and shelf life of eggs stored for 42 days

ABSTRACT: Effects of plasticizer types and whey protein concentrate (WPC) as coatings were evaluated on internal quality and shelf life of eggs stored for 42 days. Eggs were coated with WPC at 8 % solution combined with the plasticizers glycerol (GLY), sorbitol (SOR), and propylene glycol (PRO). The eggs were stored at 20 °C. Weight loss, Haugh Unit (HU), albumen and yolk pH, and yolk index (YI) were evaluated weekly from day 0 to 42 days. After, electron microscopy of the eggshell structure was performed. The data was submitted to the analysis of variance and the effects of treatment, storage time, and the interaction between these factors were evaluated. There was significant interaction between factors (treatment and periods) for weight loss (p 0.0001), HU (p 0.0001), albumen (p 0.0001), and yolk pH (p 0.0001), and YI (p 0.0001). After 42 days, uncoated eggs showed greater weight loss (5.4 %), compared to WPC+GLY, (3.8 %), WPC+SOR (3.3 %) and WPC+PRO (3.9 %). Similar results were verified for HU at 42 days of storage. Uncoated eggs showed HU of 58.46 (B), while coated eggs showed higher values: WPC+GLY 66.58 (A), WPC+SOR 68.79 (A), and WPC + PRO 71.53 (A). The plasticizers GLY, SOR and PRO, associated with WPC, demonstrated effectiveness in maintaining the quality of eggs throughout the 42 days of storage. However, WPC+SOR showed superiority in preserving quality integrity of eggs. This result can be related to the chemical structure of SOR, making the combination more efficient for storage.

Plasticizer types and whey protein coatings on internal quality and shelf life of eggs stored for 42 days

Effects of plasticizer types and whey protein concentrate (WPC) as coatings were evaluated on internal quality and shelf life of eggs stored for 42 days. Eggs were coated with WPC at 8 % solution combined with the plasticizers glycerol (GLY), sorbitol (SOR), and propylene glycol (PRO). The eggs were stored at 20 °C. Weight loss, Haugh Unit (HU), albumen and yolk pH, and yolk index (YI) were evaluated weekly from day 0 to 42 days. After, electron microscopy of the eggshell structure was performed. The data was submitted to the analysis of variance and the effects of treatment, storage time, and the interaction between these factors were evaluated. There was significant interaction between factors (treatment and periods) for weight loss (p < 0.0001), HU (p < 0.0001), albumen (p < 0.0001), and yolk pH (p < 0.0001), and YI (p < 0.0001). After 42 days, uncoated eggs showed greater weight loss (5.4 %), compared to WPC+GLY, (3.8 %), WPC+SOR (3.3 %) and WPC+PRO (3.9 %). Similar results were verified for HU at 42 days of storage. Uncoated eggs showed HU of 58.46 (B), while coated eggs showed higher values: WPC+GLY – 66.58 (A), WPC+SOR – 68.79 (A), and WPC + PRO – 71.53 (A). The plasticizers GLY, SOR and PRO, associated with WPC, demonstrated effectiveness in maintaining the quality of eggs throughout the 42 days of storage. However, WPC+SOR showed superiority in preserving quality integrity of eggs. This result can be related to the chemical structure of SOR, making the combination more efficient for storage.

The Addition of Propylene Glycol Alginate to a Fluoride Solution to Control Enamel Wear: An in situ Study.

The aim of this study was to evaluate the protective effect of propylene glycol alginate (PGA) associated with sodium fluoride (NaF) against enamel erosion and erosion-abrasion. A 4-phase, split-mouth, double-blind, crossover in situ trial was conducted with the following solutions: F + PGA (225 ppm F- + 0.1% PGA), F (225 ppm F-), F + Sn (225 ppm F- + SnCl2, 800 ppm Sn2+), and negative control (distilled water). In each phase, 12 subjects wore removable mandibular appliances containing 4 enamel specimens, which were submitted either to erosion or to erosion-abrasion challenges for 5 days. Acquired salivary pellicle was formed in situ for 2 h. Erosion-abrasion consisted of acid challenge (1% citric acid solution, pH 2.3, 5 min, 4×/day), exposure to saliva in situ (2 h, 4×/day), brushing (5 s, total 2 min exposure to the slurry), and treatment with the solutions (2 min, 2×/day). For erosion, the same procedures were performed, without brushing. At the end, surface loss (SL; in µm) was evaluated by means of optical profilometry. KOH-soluble fluoride was quantified for erosion-only groups using extra specimens. For both challenges, the SL values found for F + PGA did not differ significantly from those of F and the negative control, and the SL value shown for F + Sn was significantly the lowest. Erosion-abrasion promoted significantly higher SL values than erosion. KOH-soluble fluoride analysis showed that F + Sn had a higher fluoride concentration in comparison with the negative control and F, while F + PGA did not differ from any of the other groups. In conclusion, PGA was not able to improve the protective effect of NaF against erosive enamel wear.

Sickly Sweet: Insecticidal Polyols Induce Lethal Regurgitation in Dipteran Pests.

Polyols are commonly used in food and medicines as sweeteners and preservatives but may also have insecticidal properties against some species of Diptera. Here we compared the insecticidal activity and feeding response of glycerol and propylene glycol (PG) on two tephritids: Anastrepha ludens and Anastrepha obliqua, and the drosophilid Drosophila suzukii. First, flies were exposed to solutions of 50% sucrose and the two polyols at concentrations of 1.67 M, 2.78 M and 4.18 M for 24 h and then observed at 24 h intervals for a period of three days. Both polyols elicited strong regurgitation behavior in the three flies and killed them. Regurgitation apparently also reduced flies' body weight, and this was particularly apparent in insects that fed on 4.18 M PG solutions. A high percentage of individuals exposed to PG solutions perished after 72 hours. The number of proboscis extensions, which is associated with feeding preference, was lower in the 4.18 M polyols + sucrose mixtures than in the 50% sucrose solution. Glycerol had a lower insecticidal effect in Anastrepha spp. and very little insecticidal effect in D. suzukii. Finally, elevated regurgitation and mortality was confirmed in A. ludens treated with 1.0⁻2.78 M of erythritol plus sucrose. Our results demonstrate that PG, and to a lower extent glycerol, have the potential for being used as a safer method of insect pest control. The hyper-regurgitation response may contribute to the insecticidal properties of these polyols in Diptera.

Influence of the calcium hydroxide paste vehicle on penetration into lateral canals / Influência do veículo da pasta de hidróxido de cálcio na penetração em canais laterais

Objective: The aim of this study was to use Micro computed tomography (micro-CT) to evaluate the influence of the type of vehicle associated with calcium hydroxide on its ability to penetrate simulated lateral canals. Material and Methods: 30 acrylic blocks with simulated lateral canals comprising apical, middle and cervical thirds were used in the in vitro study. The blocks were divided into 3 groups (n = 10) according to the type of vehicle used (chlorhexidine, distilled water and propylene glycol) in the calcium hydroxide slurry, which was inserted in the respective group of simulated canals with a K# 30 file and then agitated with an ultrasonic tip. The blocks were scanned by micro-computed tomography (micro-CT) before and after insertion of the medication. The images obtained were reconstructed and analyzed to obtain the initial volume of lateral canals and the volume of medication that penetrated into them. Results: In the intragroup analysis, both distilled water and chlorhexidine 2% were observed to present statistical difference in all thirds of the canal. Propylene glycol showed no intragroup difference. In the inter-group analysis, the propylene glycol paste presented higher values of penetration into the simulated lateral canals than the other groups (p <0.05). Conclusion: Propylene glycol used as vehicle of the calcium hydroxide paste provided better penetration results in simulated lateral canals (AU).

Objetivo: O objetivo desse estudo foi avaliar por meio da microtomografia computadorizada a influência do tipo de veículo associado ao hidróxido de cálcio na capacidade de penetrar em canais laterais simulados. Material e Métodos: No estudo foram utilizados 30 blocos de acrílico com canais laterais simulados nos terços apical, médio e cervical. Os blocos foram divididos em 3 grupos (n=10) de acordo com o tipo de veículo utilizado (clorexidina, água destilada e propilenoglicol) na pasta de hidróxido de cálcio, foram inseridos com auxílio de uma lima tipo k 30 e em seguida agitadas com ultrassom. Os blocos foram escaneados em microtomografia computadorizada antes e após a inserção da medicação. As imagens obtidas foram reconstruídas e analisadas obtendo o volume inicial dos canais laterais e o volume de medicação que penetrou nos mesmos. Resultados: Na análise estatística intragrupo observou-se que tanto a água destilada quanto a clorexidina 2% apresentaram diferença estatística em todos os terços do canal. O propilenoglicol não apresentou diferença intragrupo. Já na análise entre os grupos, a pasta com propilenoglicol apresentou maior penetração nos canais laterais simulados (p<0,05). Conclusão: O propilenoglicol utilizado como veículo da pasta de hidróxido de cálcio permitiu melhores resultados de penetração em canais laterais simulados. (AU).

Spectrophotometric evaluation of calcium ion release from different calcium hydroxide preparations: an in-vitro study

Abstract: Pulp tissue conditions such as infections have long been treated with calcium hydroxide (CaOH). In the last decade, use of mineral trioxide aggregate (MTA) has gained ground. This study was carried out to comparatively evaluate the Ca release from CaOH powder with different vehicles and different types of MTA. Materials and Methods: 40 single rooted mandibular premolars were selected, decoronated and biomechanically prepared. They were randomly divided into four groups, consisting of 10 samples each. Root canals were packed with different preparations of CaOH and MTA. Calcium ion release was evaluated with an UV-spectrophotometer. Result: Amongst the CaOH preparations, using propylene glycol as a vehicle produced extended release of calcium ions (7.34 +/- 0.01) for a period of 14 days. Whereas, amongst MTA based products, MTA angelus produced the maximum release of calcium ions (2.42 +/- 0.010). A statistically significant difference was present between the four groups (p<0.05). Conclusion: Propylene glycol mixed with CaOH powder, produces a higher and extended release of calcium ions compared to distilled water. MTA angelus produces consistent calcium ion release.

Polarity-sensitive nanocarrier for oral delivery of Sb(V) and treatment of cutaneous leishmaniasis.

There is a great need for orally active drugs for the treatment of the neglected tropical disease leishmaniasis. Amphiphilic Sb(V) complexes, such as 1:3 Sb-N-octanoyl-N-methylglucamide complex (SbL8), are promising drug candidates. It has been previously reported that SbL8 forms kinetically stabilized nanoassemblies in water and that this simple dispersion exhibits antileishmanial activity when given by oral route to a murine model of visceral leishmaniasis. The main objective of the present work was to interfere in the structural organization of these nanoassemblies so as to investigate their influence on the oral bioavailability of Sb, and ultimately, optimize an oral formulation of SbL8 for the treatment of cutaneous leishmaniasis. The structural organization of SbL8 nanoassemblies was manipulated through addition of propylene glycol (PG) to the aqueous dispersion of SbL8. The presence of 50% (v/v) PG resulted in the loss of hydrophobic microenvironment, as evidenced by fluorescence probing. However, nanostructures were still present, as demonstrated by dynamic light scattering, small-angle X-ray scattering, and atomic force microscopy (AFM). A remarkable property of these nanoassemblies, as revealed by AFM analysis, is the flexibility of their supramolecular organization, which showed changes as a function of the solvent and substrate polarities. The formulation of SbL8 in 1:1 water:PG given orally to mice promoted significantly higher and more sustained serum levels of Sb, when compared to SbL8 in water. The new formulation, when given as repeated doses (200 mg Sb/kg/day) to BALB/c mice infected with Leishmania amazonensis, was significantly more effective in reducing the lesion parasite burden, compared to SbL8 in water, and even, the conventional drug Glucantime(®) given intraperitoneally at the same dose. In conclusion, this work introduces a new concept of polarity-sensitive nanocarrier that was successfully applied to optimize an oral formulation of Sb(V) for treating cutaneous leishmaniasis.

Evaluation of three therapeutic alternatives for the early treatment of ovine pregnancy toxaemia.

BACKGROUND: Ovine pregnancy toxaemia is a common metabolic disorder of ewes due to increased foetal energy requirements in late pregnancy. This pathology is a metabolic condition characterized by hypoglycaemia and hyperketonaemia resulting in the inability of the animal to maintain an adequate energy balance. The response to treatment is effective, if it is started in the early stages of the disease, when irreversible neurological injuries have not yet been established. The aim was to evaluate three therapeutic alternatives to effectively reverse the disease process in its early stages. For this, thirty adult Corriedale ewes, pregnant with a single lamb, were randomly separated in three groups of ten animals each, at day 130 of gestation. From that day onwards, ewes were locked up for forage fasting until glycaemia reached clinical values defining sub-clinical pregnancy toxaemia (1.59 ± 0.24 mmol/L). After fasting, ewes grazed and received a treatment for 4 days: 50 ml i.v. infusions of hypertonic glucose and 20 UI insulin/ewe/day s.c. or 100 ml/sheep/12 h of glycerol together with propylene glycol oral solution or fed with pasture supplemented with two daily intakes 300 g/sheep of cracked corn. Glycaemia and ß-hydroxybutyrate were determined in all the animals from the beginning of fasting until the completion of the treatment. RESULTS: Fasting caused a decline in blood glucose in the 3 groups. This decline continued until fasting was withdrawn and treatment began. Thereafter blood glucose increased in all three groups, although in the group supplemented with glycerol and propylene glycol it started to increase significantly after 12 h. The values of ß-hydroxybutyrate decreased in the 3 groups at the start of treatment, and this decline was more pronounced earlier on and in the group supplemented with glycerol and propylene glycol. We found no significant differences between all experimental groups. No animal showed clinical signs of pregnancy toxaemia throughout the research. CONCLUSIONS: The three treatments administered to sheep affected by sub-clinical pregnancy toxaemia were able to restore normal concentration of glucose and ß-hydroxybutyrate in blood, although per os administration of 100 ml/sheep/12 h of glycerol with propylene glycol, was the most successful treatment, normalizing the aforementioned biochemical parameters in a shorter time.

Characterization of smart auto-degradative hydrogel matrix containing alginate lyase to enhance levofloxacin delivery against bacterial biofilms.

The aim of the present work is the characterization of smart auto-degradable microspheres composed of calcium alginate/high methoxylated pectin containing an alginate lyase (AL) from Sphingobacterium multivorum and levofloxacin. Microspheres were prepared by ionotropic gelation containing AL in its inactive form at pH 4.0. Incubation of microspheres in Tris-HCl and PBS buffers at pH 7.40 allowed to establish the effect of ion-chelating phosphate on matrix erodability and suggested an intrinsically activation of AL by turning the pH close to neutrality. Scanning electron and optical microscopies revealed the presence of holes and surface changes in AL containing microspheres. Furthermore, texturometric parameters, DSC profiles and swelling properties were showing strong changes in microspheres properties. Encapsulation of levofloxacin into microspheres containing AL showed 70% efficiency and 35% enhancement of antimicrobial activity against Pseudomonas aeruginosa biofilm. Levofloxacin release from microspheres was not changed at acidic pH, but was modified at neutral pH in presence of AL. Advantageously, only gel matrix debris were detectable after overnight incubation, indicating an autodegradative gel process activated by the pH. Absence of matrix cytotoxicity and a reduction of the levofloxacin toxicity after encapsulation were observed in mammalian CHO-K1 cell cultures. These properties make the system a potent and versatile tool for antibiotic oral delivery targeted to intestine, enhancing the drug bioavailability to eradicate bacterial biofilm and avoiding possible intestinal obstructions.

Tetronic® 904-containing polymeric micelles overcome the overexpression of ABCG2 in the blood-brain barrier of rats and boost the penetration of the antiretroviral efavirenz into the CNS.

AIM: To assess the involvement of ABCG2 in the pharmacokinetics of efavirenz in the blood-brain barrier (BBB) and investigate a nanotechnology strategy to overcome its overexpression under a model of chronic oral administration. Materials & methods A model of chronic efavirenz (EFV) administration was established in male Sprague-Dawley rats treated with a daily oral dose over 5 days. Then, different treatments were conducted and drug concentrations in plasma and brain measured. RESULTS: Chronic treatment with oral EFV led to the overexpression of ABCG2 in the BBB that was reverted after a brief washout period. Moreover, gefitinib and the polymeric amphiphile Tetronic(®) 904 significantly inhibited the activity of the pump and potentiated the accumulation of EFV in CNS. The same effect was observed when the drug was administered within mixed micelles containing TetronicT904 as the main component. CONCLUSION: Tetronic 904-containing polymeric micelles overcame the overexpression of ABCG2 in the BBB caused by chronic administration of EFV then boosting its penetration into the CNS.

Characterization of Propylene Glycol-Mitigated Freeze/Thaw Agglomeration of a Frozen Liquid nOMV Vaccine Formulation by Static Light Scattering and Micro-Flow Imaging.

UNLABELLED: The purpose of this work was to investigate the susceptibility of an aluminum adjuvant and an aluminum-adjuvanted native outer membrane vesicle (nOMV) vaccine formulation to freeze/thaw-induced agglomeration using static light scattering and micro-flow Imaging analysis; and to evaluate the use of propylene glycol as a vaccine formulation excipient by which freeze/thaw-induced agglomeration of a nOMV vaccine formulation could be mitigated. Our results indicate that including 7% v/v propylene glycol in an nOMV containing aluminum adjuvanted vaccine formulation, mitigates freeze/thaw-induced agglomeration. LAY ABSTRACT: We evaluated the effect of freeze-thawing on an aluminum adjuvant and an aluminum adjuvanted native outer membrane vesicle (nOMV) vaccine formulation. Specifically, we characterized the freeze/thaw-induced agglomeration through the use of static light scattering, micro-flow imaging, and cryo-electron microscopy analysis. Further, we evaluated the use of 0-9% v/v propylene glycol as an excipient which could be included in the formulation for the purpose of mitigating the agglomeration induced by freeze/thaw. The results indicate that using 7% v/v propylene glycol as a formulation excipient is effective at mitigating agglomeration of the nOMV vaccine formulation, otherwise induced by freeze-thawing.