Lyoprotective Effects of Mannitol and Lactose Compared to Sucrose and Trehalose: Sildenafil Citrate Liposomes as a Case Study.
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ABSTRACT:
SUBMITTER: de Jesus Valle MJ
PROVIDER: S-EPMC8400243 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AIM: To investigate the time course of the hypotensive interaction between sildenafil and glyceryl trinitrate (GTN). METHODS: Two double-blind, placebo-controlled, randomized, crossover studies were performed. Subjects were challenged with sublingual GTN 400 microg at different times after oral sildenafil 100 mg. After each GTN challenge frequent measures of blood pressure (BP) were made. In the first study GTN was given 1-48 h after sildenafil/placebo to 33 healthy men. In the second study GTN was given 1-8 h after sildenafil/placebo to 20 men with stable angina. RESULTS: In healthy men there was a greater mean maximum reduction in BP with sildenafil/GTN than with placebo/GTN only at 1 h. In angina patients, there was a greater mean maximum reduction in BP with sildenafil/GTN than with placebo/GTN for up to 8 h. The mean (95% confidence interval) differences in maximum systolic BP reduction (mmHg) at 1, 4, 6 and 8 h were -16 (-12, -21), -12 (-4, -20), -6 (1, -12) and -9 (-3, -15), all P < 0.05 except at 6 h (NS). At 6 and 8 h the interaction was not more than additive, and hypotensive symptoms did not occur. CONCLUSIONS: In men with angina there is an interaction on BP reduction between sildenafil and GTN for >or= 8 h after sildenafil administration, but this is no more than additive from 6 h. These data may be helpful to clinicians who are considering the use of GTN in patients presenting with angina who have received sildenafil within 24 h.
| S-EPMC2679103 | biostudies-literature
Project description:BackgroundAn increase in vascular resistance of uterine vessels is associated with intrauterine growth restriction (IUGR). Sildenafil citrate, a phosphodiesterase-5 inhibitor that stabilizes cyclic guanosine monophosphate (cGMP) and increases nitric oxide levels, improves placental perfusion by dilation of spiral arteries and is beneficial in managing IUGR. This study aims to determine the effectiveness of sildenafil citrate in improving perinatal outcomes in IUGR pregnancies.MethodsMeta-analysis was performed on data extracted from all studies specific to sildenafil citrate in IUGR management, searching relevant articles on PubMed, Medline, Google Scholar, Embase, and Cochrane databases. Publications identified by the manual search, based on references in reviews, were also included. Dichotomous results were presented as risk ratio (95% confidence interval), while continuous results were expressed as mean difference (MD); samples represented by the random effects model.ResultsNine trials were included where the sildenafil citrate effect was compared with a placebo or no intervention. A significant increase in birth weight [SMD (95% CI), 0.69 (0.31, 1.07)] was seen in IUGR pregnancies managed with sildenafil. However, gestational age (SMD (95% CI), 0.44 (-0.05, 0.94], fetal death rate [RR (95% CI), 0.56 (0.17, 1.79)] in IUGR pregnancies was not changed by sildenafil. Neonatal death [RR (95% CI), 0.93 (0.47, 1.86)] and neonatal intensive care unit (NICU) admissions [RR (95% CI), 0.76 (0.50, 1.17)] were not significantly different between sildenafil and control groups.ConclusionSildenafil citrate increases birth weight and prolonged pregnancies but did not affect stillbirth rate, neonatal death, and NICU admission.Trial registrationThe study was registered in PROSPERO on September 18, 2021 (CRD42021271992).
| S-EPMC10236759 | biostudies-literature
Project description:The aim of this study was to evaluate the influence of novel engineered fine mannitol particles (4.7%, w/w) on the performance of lactose-salbutamol sulphate dry powder inhaler (DPI) formulations to obtain promising aerosolisation properties. The results showed that the more elongated the fine mannitol particles, the weaker the drug-carrier adhesion, the better the drug content homogeneity, the higher the amount of drug expected to be delivered to the lower airways and the higher the total DPI formulation desirability. Linear relationships were established showing that mannitol particles with a more elongated shape generated powders with broader size distributions and that were less uniform in shape. The weaker the drug-carrier adhesion, the higher the fine particle fraction of the drug is upon aerosolisation. It is believed that more elongated fine mannitol particles reduce the number of drug-carrier and drug-drug physical contact points and increase the ability of the drug particles to travel into the lower airways. Additionally, a lower drug-carrier contact area, lower drug-carrier press-on forces and easier drug-carrier detachment are suggested in the case of formulations containing more elongated fine mannitol particles. Ternary 'drug-coarse carrier-elongated fine ternary component' DPI formulations were more favourable than both 'drug-coarse carrier' and 'drug-elongated coarse carrier' binary formulations. This study provides a comprehensive approach for formulators to overcome the undesirable properties of dry powder inhalers, as both improved aerosolisation performance and reasonable flow characteristics were obtained using only a small amount of elongated engineered fine mannitol particles.
| S-EPMC3691434 | biostudies-literature
Project description:The two sugar molecules sucrose and trehalose are both considered as stabilizing molecules for the purpose of preserving biological materials during, for example, lyophilization or cryo-preservation. Although these molecules share a similar molecular structure, there are several important differences in their properties when they interact with water, such as differences in solubility, viscosity, and glass transition temperature. In general, trehalose has been shown to be more efficient than other sugar molecules in preserving different biological molecules against stress, and thus by investigating how these two disaccharides differ in their water interaction, it is possible to further understand what makes trehalose special in its stabilizing properties. For this purpose, the structure of aqueous solutions of these disaccharides was studied by using neutron and X-ray diffraction in combination with empirical potential structure refinement (EPSR) modeling. The results show that there are surprisingly few differences in the overall structure of the solutions, although there are indications for that trehalose perturbs the water structure slightly more than sucrose.
| S-EPMC7311057 | biostudies-literature
Project description:The aim of our study was to determine whether sildenafil citrate influences the production of Th1- (TNF-α, INF-γ) or Th2-type (TGF-β, IL-10) cytokines by lymphocytes of healthy men. Sildenafil citrate (SC) is a selective blocker of phosphodiesterase 5, by competing for the binding site with cGMP. It was reported that a higher risk of sexually transmitted diseases (STD) could be correlated with a recreational use of sildenafil, especially when combined with another drug. While behavioral causes of these findings are understood, it is worth considering other causes of that phenomenon that might rely on the influence of sildenafil on the immune system. Material and Methods. Peripheral blood mononuclear cells (PBMCs) were isolated from 27 healthy men donors and cultured in the presence of SC at a concentration of 400 ng/ml. The first set of research was performed on cells stimulated, for at least 4 hours, by incubation with phorbol myristate acetate (PMA), ionomycin, and Golgi-Stop. Subsequently, we determined cytokine production in cells stimulated with phytohemagglutinin (PHA) for 12 hours in the presence of Golgi-Stop. Flow cytometry immunophenotyping of PBMC was performed towards the surface marker of T cells: CD3 and intracellular cytokine expression: TNF-α, IFN-γ, TGF-β, and IL-10. Our findings show that SC significantly decreased the percentage of T cells producing TNF-α and displayed tendency to decrease IFN-γ, when stimulated with PMA. Frequent usage of SC might strengthen this effect. That could partially explain the impaired immune response to the pathogens of men using the drug.
| S-EPMC6930755 | biostudies-literature
Project description:Trehalose 6-phosphate (Tre6P), the intermediate of trehalose biosynthesis, has a profound influence on plant metabolism, growth, and development. It has been proposed that Tre6P acts as a signal of sugar availability and is possibly specific for sucrose status. Short-term sugar-feeding experiments were carried out with carbon-starved Arabidopsis thaliana seedlings grown in axenic shaking liquid cultures. Tre6P increased when seedlings were exogenously supplied with sucrose, or with hexoses that can be metabolized to sucrose, such as glucose and fructose. Conditional correlation analysis and inhibitor experiments indicated that the hexose-induced increase in Tre6P was an indirect response dependent on conversion of the hexose sugars to sucrose. Tre6P content was affected by changes in nitrogen status, but this response was also attributable to parallel changes in sucrose. The sucrose-induced rise in Tre6P was unaffected by cordycepin but almost completely blocked by cycloheximide, indicating that de novo protein synthesis is necessary for the response. There was a strong correlation between Tre6P and sucrose even in lines that constitutively express heterologous trehalose-phosphate synthase or trehalose-phosphate phosphatase, although the Tre6P:sucrose ratio was shifted higher or lower, respectively. It is proposed that the Tre6P:sucrose ratio is a critical parameter for the plant and forms part of a homeostatic mechanism to maintain sucrose levels within a range that is appropriate for the cell type and developmental stage of the plant.
| S-EPMC3935566 | biostudies-literature
Project description:Seeds of Arabidopsis thaliana (ecotype Columbia) were surface-sterilized inbayrochlore/ethanol (1:1, v/v), rinsed in absolute ethanol and dried overnight. Germination and growth were carried out under axenic conditions in square Petri dishes. After seeds were sowed, Petri dishes were placed at 4°C for 48 h in order to break dormancy and homogenize germination, and then transferred to a control growth chamber at 22°C under a 16-h light period regime at 4500 lux for 4 weeks. Growth medium consisted of 0.8% (w/v) agar in 1x Murashige and Skoog (MS) basal salt mix (Sigma, St. Louis, MO, USA) adjusted to pH 5.7. After 4 weeks of cultivation on vertical plates plantlets were transferred on fresh medium complemented with atrazine 10 µM and with sucrose 80mM or mannitol 80 mM which were directly added during preparation of agar-MS media prior to sterilisation. Atrazine was sterilized by microfiltration through 0.2 µm cellulose acetate filters (Polylabo, Strasbourg, France) and then axenically added to melted agar-MS medium prior to pouring into Petri dishes. Then plantlets were harvested after 12, 24 and 48 hours of transfer and extracted for RNA. Plantlets grown on MS medium were harvested and extracted for RNA as control.
2007-03-10 | E-MEXP-574 | biostudies-arrayexpress
Project description:ObjectiveFew reports are available on some benefits, such as shortened duration of diarrhea and better weight gain, for lactose-free over lactose-containing formula in acute childhood diarrhea. We evaluated the effects of lactose-free formula in dietary management of acute diarrhea in formula-fed children.MethodsThis controlled-clinical trial was conducted on formula-fed children, aged 1 to 24 months, referring with acute non-bloody diarrhea (≤2 weeks). Those who had major systemic illness, severe malnutrition, severe dehydration, severe vomiting, or history of antibiotic therapy were not included. Children were allocated to receive lactose-free formula (intervention, n=37) or lactose-containing formula (control, n=34). Time to diarrhea relief and weight change were compared between the two groups after one week.FindingsDuring the study, 32 male and 39 female children (7.1±3.7 months) were included. Those who received lactose-free formula had a significantly shorter time to diarrhea relief compared with the controls (1.7±0.7 vs. 2.6±0.7 days, P<0.001). Weight significantly increased in both groups, but there was no difference between the two groups in weight change (37±100 vs. 38±77 gr, P=0.673). Multivariate analysis showed that receiving lactose-free formula significantly predicted time to diarrhea relief (95% CI: 1.5 to 3.9, P<0.001) controlling for baseline characteristics.ConclusionEarly administration of lactose-free formula for formula-fed children presenting with acute diarrhea can result in a more rapid relief of acute diarrhea and thus perhaps less mortality and morbidity. Trials with longer follow-ups are warranted to better evaluate long-term results such as weight change and feeding problems in this regard.
| S-EPMC3448220 | biostudies-literature
Project description:The effect of sucrose and mannitol addition to low-acyl (LA) gellan gum gels at both the molecular and macroscopic levels prior to, and after freeze-drying has been investigated. It has been shown that the gel network order as well as the mechanical properties are changed with the solute content, especially in the case of sucrose. The freeze-dried gel structure, containing either mannitol or sucrose, was studied, reporting for the first time the interaction of mannitol with the gellan gum gel. The generated freeze-dried gel network was evaluated in terms of porosity, pore size and wall thickness distributions. The solute physical state was correlated the water activity trend as a function of the solute content. Since mannitol is crystalline, the water activity decreases, in contrast with the amorphous sucrose. The rehydration mechanism was investigated and associated with the solute release from the structure. Specifically, the material properties (surface and bulk) as well as the role of the dissolution medium over time were assessed. It was found that the rehydration for both the gellan/sucrose and gellan/mannitol systems was highly influenced by the additive content, as an increase in water uptake was measured up to 10 wt%. A further increase in solute led to a considerable drop in the rehydration rate and extent due to the change in the freeze-dried structure, with smaller pores and with higher wall thickness values.
| S-EPMC6061513 | biostudies-literature
Project description:The two disaccharides, trehalose and sucrose, have been compared in many studies due to their structural similarity. Both possess the ability to stabilise and reduce aggregation of proteins. Trehalose has also been shown to inhibit the formation of highly structured protein aggregates called amyloid fibrils. This study aims to compare how the thermal stability of the protein lysozyme at low pH (2.0 and 3.5) is affected by the presence of the two disaccharides. We also address the anti-aggregating properties of the disaccharides and their inhibitory effects on fibril formation. Differential scanning calorimetry confirms that the thermal stability of lysozyme is increased by the presence of trehalose or sucrose. The effect is slightly larger for sucrose. The inhibiting effects on protein aggregation are investigated using small-angle X-ray scattering which shows that the two-component system consisting of lysozyme and water (Lys/H2O) at pH 2.0 contains larger aggregates than the corresponding system at pH 3.5 as well as the sugar containing systems. In addition, the results show that the particle-to-particle distance in the sugar containing systems (Lys/Tre/H2O and Lys/Suc/H2O) at pH 2.0 is longer than at pH 3.5, suggesting larger protein aggregates in the former. Finally, the characteristic distance separating β-strands in amyloid fibrils is observed for the Lys/H2O system at pH 2.0, using wide-angle X-ray scattering, while it is not clearly observed for the sugar containing systems. This study further shows that the two disaccharides stabilise the native fold of lysozyme by increasing the denaturation temperature. However, other factors, such as a weakening of hydrophobic interactions and hydrogen bonding between proteins, might also play a role in their inhibitory effect on amyloid fibril formation.
| S-EPMC11017192 | biostudies-literature