Bioaerogels: Promising materials for impregnation of drugs

The following work examines the possibility of impregnating chosen model drug into bioaerogels to obtain final formulation with added value. The drug used in this study was esomeprazole, used to treat acid-related diseases. In the first part of the work, bioaerogels were prepared. Polysaccharide aerogels are lightweight biocompatible and biodegradable materials, suitable for applications in pharmaceutical industry. For this purpose, three different cores were prepared: pectin, alginate and their mixture, followed by coating with chitosan layer. The production of the bioaerogels follows a sol-gel synthesis and supercritical drying technique. All samples were characterised, and optimisation was performed based on examined properties. Aerogels having a pectin core and chitosan coating showed the highest surface area and the highest adsorption capacity. In the second part, the impregnation of esomeprazole was performed using two different methods: supercritical impregnation and diffusion via sol-gel synthesis. For supercritical impregnation, supercritical carbon dioxide was used as a solvent for impregnation of the drug. In the diffusion method, the model drug was added during sol-gel synthesis using ethanol as solvent. Finally, complete characterisation of prepared formulation followed by drug release studies was performed. The study showed successful impregnation of esomeprazole using either carbon dioxide or ethanol as a solvent. Bioaerogels proved to be promising as carriers for achieving the optimal release of the chosen drugV diplomskem delu smo proučevali možnost impregnacije vzorčnega zdravila v bioaerogele z namenom, da dobimo učinkovito končno formulirano obliko. Kot vzorčno zdravilo smo uporabili esomeprazol, ki se uporablja za zdravljenje bolezni povezanih z želodčno kislino. V prvem delu diplome smo pripravili bioaerogele. Polisaharidni aerogeli so lahki biokompatibilni in biorazgradljivi materiali, ki so primerni za uporabo v farmacevtski industriji. Pektin, alginat in njuno mešanico smo uporabili za pripravo treh različnih jeder, ki smo jih nato prevlekli s plastjo hitozana. Bioaerogele smo sintetizirali s sol-gel sintezo in jih sušili s superkritičnim oglijkovim dioksidom. Opravili smo karakterizacijo in optimizacijo pripravljenih vzorcev. Aerogeli s pektinskim jedrom in obdani s hitozanom imajo največjo površino in največjo adsorpcijsko sposobnost. V drugem delu smo izvedli impregnacijo esomeprazola po dveh različnih metodah in sicer z metodo superkritične impregnacije in z metodo difuzije s sol-gel sintezo. Pri superkritični impregnaciji smo kot topilo uporabili superkritični ogljikov dioksid. Pri difuzijski metodi pa smo vzorčno zdravilo dodali med sol-gel sintezo, pri čemer smo kot topilo uporabili etanol. Na koncu smo izvedli popolno karakterizacijo pripravljene formulacije in opravili študijo sproščanja zdravila. Z obema metodama smo uspešno impregnirali esomeprazol ter dosegli optimalno sproščanje izbranega zdravila.Departamento de Ingeniería Química y Tecnología del Medio AmbienteGrado en Ingeniería Químic

Sexual dimorphism in histological characteristics and contractility of the iliofibularis muscle in the lizard Sceloporus torquatus

Our results and observations support the idea that muscle characteristics are coadaptations of organisms and environment, as noted by Bonine et al. (2001). What we need to know now is whether and how the environment affects the relationship between muscle phenotype and fitness. Therefore, studies on habitat, behavioural patterns, morphological characteristics and locomotor performance are needed to better understand the plasticity of the locomotor muscles.The iliofibularis is a hindlimb muscle used in lizard locomotion that is composed of at least three types of fibres: fast-twitch-glycolytic (FG), fast-twitch-oxidativeglycolytic fibre (FOG) and slow-twitch-oxidative (SO). The striated skeletalmuscle is a highly plastic tissue undergoing phenotypic change in response to activity. The lizard Sceloporus torquatus has sexual differences associated with microhabitat use, which can be reflected in the physiology and anatomy of the muscle, and thus, in our study, we analysed the morphological and contractile characteristics of the iliofibularis muscle (IF) of S. torquatus males and females. We found a larger prevalence of FOG compared with FG and SO fibres in the muscle of both sexes. We also found that males show larger areas of the three types of fibres, develop greater strength but also faster fatigue than females, suggesting that strength is a key functional feature that enables males to perform faster movements (but for shorter periods), associated with the demands of territoriality.CONACYT 226935/21266

Association between the serum concentration of triiodothyronine with components of metabolic syndrome, cardiovascular risk, and diet in euthyroid post-menopausal women without and with metabolic syndrome

PURPOSE: To determine the association between the serum concentration of triiodothyronine (T3) with components of metabolic syndrome (MetS), cardiovascular risk (CVR), and diet in euthyroid post-menopausal women without and with MetS. METHODS: A cross-sectional study was performed in 120 voluntary women of an indigenous population from Tlaxcala-México. Euthyroid status was assessed measuring the serum concentration of thyrotropin (TSH) and thyroid hormones, while that of estradiol was measured to confirm the postmenopausal condition. MetS was diagnosed using the American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement (AHA/NHLBI) criterion. Estimation of CVR was calculated based on the Framingham scale. Diet components were evaluated based on survey applications. Correlations, logistic regression analyses, ANOVA or Kruskall-Wallis, and chi-square tests were used to determine significant differences (P ≤ 0.05) between women without MetS and women with MetS having different serum concentrations of T3. RESULTS: Triiodothyronine was positively correlated with insulin but negatively correlated with glucose, high-density lipoprotein cholesterol (HDL-C), and CVR. Compared to women without MetS, women with MetS and low-normal T3 concentration showed a high risk for hyperglycemia and moderate/high risk for CVR. In contrast, a high-normal T3 concentration increased the risk to have a big waist circumference, a high concentration of HDL-C, and insulin resistance. Diet analysis showed a high grade of malnutrition in women from all groups. The intake of calories was positively affected by the T3 concentration, albeit it did not affect the extent of malnutrition. CONCLUSIONS: In contrast to concentrations of TSH, total thyroxin (T4), and free T4, the concentration of serum T3 was strongly correlated with cardio-metabolic variables in euthyroid postmenopausal women. In comparison to women without MetS, a high-normal serum concentration of T3 in women with MetS is positively associated with reduced glycaemia and CVR but negatively related to body mass index (BMI), insulin, insulin resistance, and HDL-C. Although the analyzed population had a nutritional deficiency, both calories and iron intake were positively affected by the T3 concentration. Our results suggest the necessity of health programs monitoring T3 in old people in order to treat hyperglycemia, cardio-metabolic components, and the ageing anorexia

Crtc1 activates a transcriptional program deregulated at early Alzheimer's disease-related stages

Cognitive decline is associated with gene expression changes in the brain, but the transcriptional mechanisms underlying memory impairments in cognitive disorders, such as Alzheimer's disease (AD), are largely unknown. Here, we aimed to elucidate relevant mechanisms responsible for transcriptional changes underlying early memory loss in AD by examining pathological, behavioral, and transcriptomic changes in control and mutant β-amyloid precursor protein(APPSw,Ind) transgenic mice during aging. Genome-wide transcriptome analysis using mouse microarrays revealed deregulation of a gene network related with neurotransmission, synaptic plasticity, and learning/memory in the hippocampus of APPSw,Ind mice after spatial memory training. Specifically, APPSw,Ind mice show changes on a cAMP-responsive element binding protein(CREB)- regulated transcriptional program dependent on the CREB-regulated transcription coactivator-1 (Crtc1). Interestingly, synaptic activity and spatial memory induces Crtc1 dephosphorylation (Ser151), nuclear translocation, and Crtc1-dependent transcription in the hippocampus, and these events are impaired in APPSw,Ind mice at early pathological and cognitive decline stages. CRTC1-dependent genes and CRTC1 levels are reduced in human hippocampus at intermediate Braak III/IV pathological stages. Importantly, adeno-associated viral-mediated Crtc1 overexpression in the hippocampus efficiently reverses Aβ-induced spatial learning and memory deficits by restoring a specific subset of Crtc1 target genes. Our results reveal a critical role of Crtc1-dependent transcription on spatial memory formation and provide the first evidence that targeting brain transcriptome reverses memory loss in AD

X-linked Inhibitor of Apoptosis Protein negatively regulates neuronal differentiation through interaction with cRAF and Trk

Altres ajuts: CIBERNED CB06/05/0042 i CB06/05/1104, RENEVAS RD06/0026/1009 i Juan de la CiervaX-linked Inhibitor of apoptosis protein (XIAP) has been classically identified as a cell death regulator. Here, we demonstrate a novel function of XIAP as a regulator of neurite outgrowth in neuronal cells. In PC12 cells, XIAP overexpression prevents NGF-induced neuronal differentiation, whereas NGF treatment induces a reduction of endogenous XIAP levels concomitant with the induction of neuronal differentiation. Accordingly, downregulation of endogenous XIAP protein levels strongly increases neurite outgrowth in PC12 cells as well as axonal and dendritic length in primary cortical neurons. The effects of XIAP are mediated by the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERKs) pathway since blocking this pathway completely prevents the neuritogenesis mediated by XIAP downregulation. In addition, we found that XIAP binds to cRaf and Trk receptors. Our results demonstrate that XIAP plays a new role as a negative regulator of neurotrophin-induced neurite outgrowth and neuronal differentiation in developing neurons

High Estradiol Differentially Affects the Expression of the Glucose Transporter Type 4 in Pelvic Floor Muscles of Rats

Purpose To characterize the relationship between serum estradiol levels and the expression of glucose transporter type 4 (Glut4) in the pubococcygeus and iliococcygeus muscles in female rats. Methods The muscles were excised from virgin rats during the metestrus and proestrus stages of the estrous cycle, and from sham and ovariectomized rats implanted with empty or estradiol benzoate–filled capsules. The expression of estrogen receptors (ERs) was inspected in the muscles at metestrus and proestrus. Relative Glut4 expression, glycogen content, and serum glucose levels were measured. Appropriate statistical tests were done to identify significant differences (P≤0.05). Results The pubococcygeus and iliococcygeus muscles expressed ERα and ERβ. Glut4 expression and glycogen content in the pubococcygeus muscle were higher at proestrus than at metestrus. No significant changes were observed in the iliococcygeus muscle. In ovariectomized rats, the administration of estradiol benzoate increased Glut4 expression and glycogen content in the pubococcygeus muscle alone. Conclusions High serum estradiol levels increased Glut4 expression and glycogen content in the pubococcygeus muscle, but not in the iliococcygeus muscle