Use of probiotics in preventing and treating excess weight and obesity. A systematic review.

Background: The prevalence of excess weight and obesity is increasing in an extremely concerning manner worldwide, with highly diverse therapies for current treatment. This review evaluated the scientific evidence of the past 10 years on the use of probiotics in treating excess weight and obesity in the absence of dieting. Materials: A systematic review was conducted by searching for clinical trials on humans published in English in the PubMed, Scopus and Cochrane Central databases, using the combination of keywords "Overweight", "Probiotics" and "Obesity", and published between 2012 and 2022. Results: Six published studies met the inclusion criteria. The review showed that, although there is a lack of consensus in the literature, the use of probiotics in the absence of dieting produced a significant reduction in body weight and body mass index in 66.6% of the reviewed studies, a significant reduction in waist circumference in 80.0% of the reviewed studies, and an improvement in total body fat mass and waist circumference. Conclusions: This review showed evidence of a trend in preventing body weight gain and reducing weight through the use of probiotics in individuals with excess weight or obesity. A combination of various strains of the genera Bifidobacterium and Lactobacillus was the most effective.

Serpine1 mRNA confers mesenchymal characteristics to the cell and promotes CD8+ T cells exclusion from colon adenocarcinomas.

Serine protease inhibitor clade E member 1 (SERPINE1) inhibits extracellular matrix proteolysis and cell detachment. However, SERPINE1 expression also promotes tumor progression and plays a crucial role in metastasis. Here, we solve this apparent paradox and report that Serpine1 mRNA per se, independent of its protein-coding function, confers mesenchymal properties to the cell, promoting migration, invasiveness, and resistance to anoikis and increasing glycolytic activity by sequestering miRNAs. Expression of Serpine1 mRNA upregulates the expression of the TRA2B splicing factor without affecting its mRNA levels. Through transcriptional profiling, we found that Serpine1 mRNA expression downregulates through TRA2B the expression of genes involved in the immune response. Analysis of human colon tumor samples showed an inverse correlation between SERPINE1 mRNA expression and CD8+ T cell infiltration, unveiling the potential value of SERPINE1 mRNA as a promising therapeutic target for colon tumors.

Bioabsorbable Composites Based on Polymeric Matrix (PLA and PCL) Reinforced with Magnesium (Mg) for Use in Bone Regeneration Therapy: Physicochemical Properties and Biological Evaluation.

Improvements in Tissue Engineering and Regenerative Medicine (TERM)-type technologies have allowed the development of specific materials that, together with a better understanding of bone tissue structure, have provided new pathways to obtain biomaterials for bone tissue regeneration. In this manuscript, bioabsorbable materials are presented as emerging materials in tissue engineering therapies related to bone lesions because of their ability to degrade in physiological environments while the regeneration process is completed. This comprehensive review aims to explore the studies, published since its inception (2010s) to the present, on bioabsorbable composite materials based on PLA and PCL polymeric matrix reinforced with Mg, which is also bioabsorbable and has recognized osteoinductive capacity. The research collected in the literature reveals studies based on different manufacturing and dispersion processes of the reinforcement as well as the physicochemical analysis and corresponding biological evaluation to know the osteoinductive capacity of the proposed PLA/Mg and PCL/Mg composites. In short, this review shows the potential of these composite materials and serves as a guide for those interested in bioabsorbable materials applied in bone tissue engineering.

Metastable FeMg particles for controlling degradation rate, mechanical properties, and biocompatibility of Poly(l-lactic) acid (PLLA) for orthopedic applications.

Poly(l-lactic) acid (PLLA) is commonly used in bioabsorbable medical implants, but it suffers from slow degradation rate and rapid decline in mechanical properties for orthopedic applications. To address this drawback, recent research has explored the use of Mg as a filler for PLLA, resulting in composites with improved degradation rate and cytocompatibility compared to neat PLLA. In this study, FeMg powder particles were proposed as fillers for PLLA to investigate the potential of PLLA/FeMg composites for bioabsorbable implants. Cylinder specimens of PLLA, PLLA/Fe, PLLA/Mg and PLLA/FeMg were prepared using solvent casting followed by thermo-molding. The microstructure, thermal behavior, in vitro degradation behavior in simulated body fluid, mechanical properties and cytocompatibility of these composites were examined. The results indicate that the presence of FeMg particles prevents the deterioration of the composite mechanical properties, at least up to 14 days. Once a certain amount of degradation of the composite is reached, the degradation is faster than that of PLLA. Direct cytotoxicity assays revealed that pre-osteoblast MC3T3-E1 cells successfully adhered to and proliferated on the PLLA/FeMg surface. The inclusion of a low percentage of Mg into the Fe lattice not only accelerated the degradation rate of Fe but also improved its cytocompatibility. The enhanced degradation rate, mechanical properties, and osteoconductive properties of this composite make it a promising option for temporary orthopedic biomedical devices.

Effect of Heat Treatment on the Dry Sliding Wear Behavior of the Mg-3Zn-0.4Ca Alloy for Biodegradable Implants.

The wear behavior of the Mg-3wt.% Zn-0.4wt.% Ca (ZX30) alloy was tested using a pin-on-disc configuration with AZ31 alloy discs as counterparts under dry sliding conditions. The ZX30 alloy was tested in different states: as-cast, solution-treated, peak-aged, and over-aged. Wear rates and friction coefficients were measured at different loads and sliding speeds. Abrasion and oxidation were the main wear mechanisms found in all the conditions tested. Moreover, aluminum oxides were detected on the worn surfaces, which indicates the presence of an adhesive wear mechanism. The wear behavior of the studied ZX30 alloy showed a greater tendency towards oxidative wear than other Mg alloys, and the microstructure observed strongly affected the wear behavior.

Microstructure and Wear Behavior of Heat-Treated Mg-1Zn-1Ca Alloy for Biomedical Applications.

The microstructure and wear properties of a Mg-1wt.% Zn-1wt.% Ca (ZX11) alloy with different heat treatments have been investigated. The ZX11 alloy was tested in the as-cast state and after different heat treatment conditions: solution-treated (at 450 °C for 24 h), peak-aged (solution-treated + aged at 180 °C for 3 h), and over-aged (solution-treated + aged at 180 °C for 24 h). The microstructure of the as-cast sample showed a continuous intermetallic phase at the grain boundaries, while the heat-treated samples exhibited discrete precipitated particles within the grains. To evaluate the wear behavior, the samples were tested using a pin-on-disc configuration, where the wear rates and friction coefficients were measured at different loads and sliding speeds. An AZ31 magnesium alloy was used as the counterbody. The worn surfaces and the wear debris were studied to identify the main wear mechanisms corresponding to each test condition. The results indicated the presence of abrasion, oxidation, and adhesive wear mechanisms in all testing conditions. In the as-cast state, delamination and plastic deformation were the dominant wear mechanisms, while they were less relevant in the heat-treated conditions. The peak-aged samples exhibited the lowest wear rates, suggesting that modifying the distribution of intermetallic precipitates contributed to enhancing the wear resistance of the alloy.

TGF-ß-Upregulated Lnc-Nr6a1 Acts as a Reservoir of miR-181 and Mediates Assembly of a Glycolytic Complex.

Long non-coding RNAs (lncRNAs) have emerged as key regulators in a wide range of biological processes. Here, we identified a mouse miRNA-host gene lncRNA (lnc-Nr6a1) upregulated early during epithelial-to-mesenchymal transition (EMT). We show that when lncRNA is processed, it gives rise to two abundant polyadenylated isoforms, lnc-Nr6a1-1 and lnc-Nr6a1-2, and a longer non-polyadenylated microprocessor-driven lnc-pri-miRNA containing clustered pre-miR-181a2 and pre-miR-181b2 hairpins. Ectopic expression of the lnc-Nr6a1-1 or lnc-Nr6a1-2 isoform enhanced cell migration and the invasive capacity of the cells, whereas the expression of the isoforms and miR-181a2 and miR-181b2 conferred anoikis resistance. Lnc-Nr6a1 gene deletion resulted in cells with lower adhesion capacity and reduced glycolytic metabolism, which are restored by lnc-Nr6a1-1 isoform expression. We performed identification of direct RNA interacting proteins (iDRIP) to identify proteins interacting directly with the lnc-Nr6a1-1 isoform. We defined a network of interacting proteins, including glycolytic enzymes, desmosome proteins and chaperone proteins; and we demonstrated that the lnc-Nr6a1-1 isoform directly binds and acts as a scaffold molecule for the assembly of ENO1, ALDOA, GAPDH, and PKM glycolytic enzymes, along with LDHA, supporting substrate channeling for efficient glycolysis. Our results unveil a role of Lnc-Nr6a1 as a multifunctional lncRNA acting as a backbone for multiprotein complex formation and primary microRNAs.

The Role of the Sol-Gel Synthesis Process in the Biomedical Field and Its Use to Enhance the Performance of Bioabsorbable Magnesium Implants.

In the present day, the increment in life expectancy has led to the necessity of developing new biomaterials for the restoration or substitution of damaged organs that have lost their functionalities. Among all the research about biomaterials, this review paper aimed to expose the main possibilities that the sol-gel synthesis method can provide for the fabrication of materials with interest in the biomedical field, more specifically, when this synthesis method is used to improve the biological properties of different magnesium alloys used as biomaterials. The sol-gel method has been widely studied and used to generate ceramic materials for a wide range of purposes during the last fifty years. Focused on biomedical research, the sol-gel synthesis method allows the generation of different kinds of biomaterials with diverse morphologies and a high potential for the biocompatibility improvement of a wide range of materials commonly used in the biomedical field such as metallic implants, as well as for the generation of drug delivery systems or interesting biomaterials for new tissue engineering therapies.

Manufacturing of Aluminum Matrix Composites Reinforced with Carbon Fiber Fabrics by High Pressure Die Casting.

Aluminum matrix composites reinforced with carbon fiber have been manufactured for the first time by infiltrating an A413 aluminum alloy in carbon fiber woven using high-pressure die casting (HPDC). Composites were manufactured with unidirectional carbon fibers and with 2 × 2 twill carbon wovens. The HPDC allowed full wetting of the carbon fibers and the infiltration of the aluminum alloy in the fibers meshes using aluminum at 680 °C. There was no discontinuity at the carbon fiber-matrix interface, and porosity was kept below 0.1%. There was no degradation of the carbon fibers by their reaction with molten aluminum, and a refinement of the microstructure in the vicinity of the carbon fibers was observed due to the heat dissipation effect of the carbon fiber during manufacturing. The mechanical properties of the composite materials showed a 10% increase in Young's modulus, a 10% increase in yield strength, and a 25% increase in tensile strength, which are caused by the load transfer from the alloy to the carbon fibers. There was also a 70% increase in elongation for the unidirectionally reinforced samples because of the finer microstructure and the load transfer to the fibers, allowing the formation of larger voids in the matrix before breaking. The comparison with different mechanical models proves that there was an effective load transference from the matrix to the fibers.

Anticorrosion and Cytocompatibility Assessment of Graphene-Doped Hybrid Silica and Plasma Electrolytic Oxidation Coatings for Biomedical Applications.

Magnesium AZ31 alloy substrates were coated with different coatings, including sol-gel silica-reinforced with graphene nanoplatelets, sol-gel silica, plasma electrolytic oxidation (PEO), and combinations of them, to improve cytocompatibility and control the corrosion rate. Electrochemical corrosion tests, as well as hydrogen evolution tests, were carried out using Hanks' solution as the electrolyte to assess the anticorrosion behavior of the different coating systems in a simulated body fluid. Preliminary cytocompatibility assessment of the different coating systems was carried out by measuring the metabolic activity, deoxyribonucleic acid quantification, and the cell growth of premyoblastic C2C12-GFP cell cultures on the surface of the different coating systems. Anticorrosion behavior and cytocompatibility were improved with the application of the different coating systems. The use of combined PEO + SG and PEO + SG/GNP coatings significantly decreased the degradation of the specimens. The monolayer sol-gel coatings, with and without GNPs, presented the best cytocompatibility improvement.

Comparison of Different Additive Manufacturing Methods for 316L Stainless Steel.

In additive manufacturing (AM), the technology and processing parameters are key elements that determine the characteristics of samples for a given material. To distinguish the effects of these variables, we used the same AISI 316L stainless steel powder with different AM techniques. The techniques used are the most relevant ones in the AM of metals, i.e., direct laser deposition (DLD) with a high-power diode laser and selective laser melting (SLM) using a fiber laser and a novel CO2 laser, a novel technique that has not yet been reported with this material. The microstructure of all samples showed austenitic and ferritic phases, which were coarser with the DLD technique than for the two SLM ones. The hardness of the fiber laser SLM samples was the greatest, but its bending strength was lower. In SLM with CO2 laser pieces, the porosity and lack of melting reduced the fracture strain, but the strength was greater than in the fiber laser SLM samples under certain build-up strategies. Specimens manufactured using DLD showed a higher fracture strain than the rest, while maintaining high strength values. In all the cases, crack surfaces were observed and the fracture mechanisms were determined. The processing conditions were compared using a normalized parameters methodology, which has also been used to explain the observed microstructures.

Modulation of Crystallinity through Radiofrequency Electromagnetic Fields in PLLA/Magnetic Nanoparticles Composites: A Proof of Concept.

To modulate the properties of degradable implants from outside of the human body represents a major challenge in the field of biomaterials. Polylactic acid is one of the most used polymers in biomedical applications, but it tends to lose its mechanical properties too quickly during degradation. In the present study, a way to reinforce poly-L lactic acid (PLLA) with magnetic nanoparticles (MNPs) that have the capacity to heat under radiofrequency electromagnetic fields (EMF) is proposed. As mechanical and degradation properties are related to the crystallinity of PLLA, the aim of the work was to explore the possibility of modifying the structure of the polymer through the heating of the reinforcing MNPs by EMF within the biological limit range f·H < 5·× 109 Am-1·s-1. Composites were prepared by dispersing MNPs under sonication in a solution of PLLA. The heat released by the MNPs was monitored by an infrared camera and changes in the polymer were analyzed with differential scanning calorimetry and nanoindentation techniques. The crystallinity, hardness, and elastic modulus of nanocomposites increase with EMF treatment.

Local Induction Heating Capabilities of Zeolites Charged with Metal and Oxide MNPs for Application in HDPE Hydrocracking: A Proof of Concept.

Zeolites are widely used in high-temperature oil refining processes such as fluid catalytic cracking (FCC), hydrocracking, and aromatization. Significant energy cost are associated with these processes due to the high temperatures required. The induction heating promoted by magnetic nanoparticles (MNPs) under radio frequency fields could contribute to solving this problem by providing a supplementary amount of heat in a nano-localized way, just at the active centre site where the catalytic process takes place. In this study, the potential of such a complementary route to reducing energetic requirements is evaluated. The catalytic cracking reaction under a hydrogen atmosphere (hydrocracking) applied to the conversion of plastics was taken as an application example. Thus, a commercial zeolite catalyst (H-USY) was impregnated with three different magnetic nanoparticles: nickel (Ni), cobalt (Co), maghemite (γ-Fe2O3), and their combinations and subjected to electromagnetic fields. Temperature increases of approximately 80 °C were measured for H-USY zeolite impregnated with γ-Fe2O3 and Ni-γ-Fe2O3 due to the heat released under the radio frequency fields. The potential of the resulting MNPs derived catalyst for HDPE (high-density polyethylene) conversion was also evaluated by thermogravimetric analysis (TGA) under hydrogen atmosphere. This study is a proof of concept to show that induction heating could be used in combination with traditional resistive heating as an additional energy supplier, thereby providing an interesting alternative in line with a greener technology.

Consenso venezolano para el uso de la resonancia magnética en el diagnóstico y seguimiento de pacientes con esclerosis múltiple / Venezuelan consensus guidelines on the use of magnetic resonance in diagnosis and follow up of patients with multiple sclerosis

Introducción. El uso de la resonancia magnética (RM) en el diagnóstico y seguimiento de pacientes con esclerosis múltiple (EM) se ha incrementado considerablemente durante los últimos años. Diversos grupos de trabajo internacionales han intentado clarificar y normativizar el uso de la RM tanto en el momento del diagnóstico como durante el seguimiento de los pacientes. Sin embargo, en muchas ocasiones se extrapolan datos de otras regiones que no contemplan la realidad de cada lugar o son difíciles de implementar. Objetivo. Elaborar un consenso venezolano para el uso de la RM en el diagnóstico y seguimiento de pacientes con EM. Desarrollo. Un grupo de expertos de Venezuela, conformado por neurólogos y radiólogos, mediante metodología de ronda de encuestas a distancia y reuniones presenciales, llevó adelante la elaboración del consenso pretendido para el uso de la RM en el diagnóstico y seguimiento de pacientes con EM en Venezuela. Se establecieron 17 recomendaciones basadas en la evidencia publicada y en el criterio de los expertos que participaron. Las recomendaciones se enfocaron en el papel de las técnicas convencionales de RM, así como en el de la medición de la atrofia cerebral en pacientes con EM, tanto en el momento del diagnóstico como durante el seguimiento. Conclusión. Las recomendaciones establecidas en el presente consenso permitirán optimizar el cuidado y el seguimiento de los pacientes con EM en Venezuela (AU)

Introduction. The clinical use of magnetic resonance (MR) in patients with multiple sclerosis (MS) has advanced markedly over the past few years. Several groups around the world have developed consensus guidelines about the role of MR in MS at diagnosis and during follow up. However, in some regions is difficult to extrapolate the recommendations. Aim. To provide recommendations for the implementation of MR in MS patients at diagnosis and follow up in Venezuela. Development. A group of experts from Venezuela that included neurologists and radiologists, by using the online surveys methodology as well as face to face meetings developed the intended consensus for the use of MR during the diagnosis and follow up of MS patients in Venezuela. Seventeen recommendations were established based on published evidence and the expert opinion. Recommendations focused on the role of conventional MR techniques and brain atrophy measurement in MS patients both at diagnosis and during follow-up. Conclusions. The recommendations of this consensus guidelines attempts to optimize the health care and management of patients with MS in Venezuela (AU)

Downregulation of Lnc-Spry1 mediates TGF-ß-induced epithelial-mesenchymal transition by transcriptional and posttranscriptional regulatory mechanisms.

Long non-coding RNAs (lncRNAs) are a class of regulatory genes that participate in a wide range of biological processes, including proliferation, differentiation and development, as well as in a broad spectrum of diseases. Although the role of lncRNAs in TGF-ß-induced epithelial-to-mesenchymal transition (EMT) has been well established, little is known about the role of lncRNAs as immediate-early regulators of EMT. Here lnc-Spry1 is identified as an immediate-early regulator of EMT that is downregulated by TGF-ß. It is also found that knockdown of lnc-Spry1 promotes a mesenchymal-like phenotype and results in increased cell migration and invasion. In addition, it is shown that lnc-Spry1 depletion preferentially affects the expression of TGF-ß-regulated gene targets. Moreover, lnc-Spry1 associates with U2AF65 splicing factor, suggesting a role in alternative splicing. Depletion of lnc-Spry1 induces, as TGF-ß, isoform switching of fibroblast growth factor receptors, resulting in FGF-2-sensitive cells. Taken together, these results show that lnc-Spry1 could act as an early mediator of TGF-ß signaling and reveal different roles for a lncRNA in modulating transcriptional and posttranscriptional gene expression.

Micromorphology of immature stages of Sarcophaga (Liopygia) cultellata Pandellé, 1896 (Diptera: Sarcophagidae), a forensically important fly.

The Sarcophagidae are one of the most numerous groups of Diptera in the world, consisting of many species of forensic interest, whose immature stages are useful in the estimation of postmortem interval. The immature stages of some species of forensic importance still remain unknown or undescribed, like in the case of Sarcophaga (Liopygia) cultellata Pandellé, 1986, a species restricted to the Iberian Peninsula, south of France and north of Italy, which shares a ecological niche with species of the same subgenus, e.g., Sarcophaga (Liopygia) argyrostoma (Robineau-Desvoidy, 1830) and Sarcophaga (Liopygia) crassipalpis Macquart, 1839, making it necessary to lay the groundwork for a proper specific differentiation before it can be successfully applied in forensic practice. This study provides the first micromorphological description of all preimaginal stages of S. (L.) cultellata using light microscopy and scanning electron microscopy (SEM), the results of which allow the morphology of the main features to be followed during the immature life cycle. We propose a combination of features for distinguishing Liopygia from other sarcophagid subgenera, based on the current level of morphological knowledge of immature stages. S. (L.) cultellata can be differentiated from S. (L.) argyrostoma and S. (L.) crassipalpis in every immature stage by both light microscopy and SEM. The presence of tegumental warts and a fan-shaped anterior spiracle with a single row of 15-18 respiratory papillae allow distinguishing the third instar larvae of S. (L.) cultellata from other Sarcophaga species described hitherto by SEM. Identification keys based on light microscopy observations are provided, covering all the immature stages of Liopygia subgenus occurring in the Iberian Peninsula.

Novel small RNA expression libraries uncover hsa-miR-30b and hsa-miR-30c as important factors in anoikis resistance.

MicroRNAs (miRNAs) have been widely studied in order to elucidate their biological functions. MicroRNA microarrays or miRNA overexpression libraries generated by synthesis and cloning of individual miRNAs have been used to study their different roles. In this work, we have developed a novel methodology to express mature miRNAs and other small RNAs from a double convergent RNA polymerase III promoter. We show that the generated miRNAs function similarly to those processed from primary transcripts or pri-miRNAs. This system allowed us to produce a lentiviral library expressing the whole population of small RNAs present in a metastatic cell line. A functional screening using this library led to the identification of hsa-miR-30b and hsa-miR-30c as negative regulators of cell death induced by loss of attachment (anoikis). Importantly, we demonstrated that the acquisition of anoikis resistance via these miRNAs is achieved through down-regulation of caspase 3 expression. Moreover, overexpression of these miRNAs resulted in a decrease of other types of caspase 3-dependent cell death and enhanced the survival of MCF10A acinar cells in morphogenesis assays, suggesting a putative role as oncomirs. In summary, this novel methodology provides a powerful and effective way for identifying novel small RNAs involved in a particular biological process.

PTTG1/securin modulates microtubule nucleation and cell migration.

Pituitary tumor transforming gene 1 (PTTG1), also known as securin, has been implicated in many biological functions, including inhibition of sister chromatid separation, DNA repair, organ development, and regulation of the expression and secretion of angiogenic and metastatic factors. Although most of these functions of securin seem to depend on the localization of PTTG1 in the nucleus of the cell, a fraction of the protein has been also detected in the cytoplasm. Here we demonstrate that, in different cell types, a portion of cytoplasmic PTTG1 is associated with the cis face of the Golgi apparatus and that this localization depends on PTTG1 phosphorylation status. In this organelle, PTTG1 forms a complex with proteins involved in microtubule nucleation, including GM130, AKAP450, and γ-tubulin. RNA interference-mediated depletion of PTTG1 produces a delay in centrosomal and noncentrosomal microtubule nucleation. Cells lacking PTTG1 show severe defects in both cell polarization and migration in wound-healing assays. To our knowledge, this is the first study reporting the role of PTTG1 in microtubule nucleation and cell polarization, two processes directly involved in cell migration. We believe that these findings will contribute to understanding the mechanisms underlying PTTG1-mediated biological functions.

Identification of HAVCR1 gene haplotypes associated with mRNA expression levels and susceptibility to autoimmune diseases.

Human HAVCR1 gene maps on 5q33.2, a region linked with susceptibility to allergic and autoimmune diseases. The aims of the present study were to define the haplotypes of HAVCR1 gene taking into account both HapMap Project SNP haplotypes and exon 4 variants, to investigate a possible relationship between these haplotypes and mRNA expression levels, and to assess whether HAVCR1 gene is involved in susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Genotyping of three ins/del variants in the exon 4 was performed by fragment length analysis. Five tag SNPs genotypes and mRNA levels were determined using TaqMan assays. We defined four major haplotypes in our population: the two major haplotypes (named haplotypes A and B) bear both the 5383_5397del variant and the two most common SNP sets found in the CEU population. Quantification analysis revealed that genotype B/B had the highest median of mRNA expression levels (vs. BX + XX, p < 0.0001). Additionally, frequency of the genotype BB was significantly higher in RA patients than in controls (12.3 vs. 5.9% in controls, p = 0.0046, p (c) = 0.014, OR = 2.23, 95% CI 1.23-4.10). Our results support a relationship between HAVCR1 haplotypes and mRNA expression levels, and suggest an association of this gene with autoimmune diseases.

Pre-synaptic histamine H3 receptors regulate glutamate, but not GABA release in rat thalamus.

We have investigated the presence of histamine H(3) receptors (H(3)Rs) on rat thalamic isolated nerve terminals (synaptosomes) and the effect of their activation on glutamate and GABA release. N-alpha-[methyl-(3)H]histamine ([(3)H]-NMHA) bound specifically to synaptosomal membranes with dissociation constant (K(d)) 0.78+/-0.20 nM and maximum binding (B(max)) 141+/-12fmol/mg protein. Inhibition of [(3)H]-NMHA binding by histamine and the H(3)R agonist immepip fit better to a two-site model, whereas for the H(3)R antagonist clobenpropit the best fit was to the one-site model. GTPgammaS (30 microM) decreased [(3)H]-NMHA binding by 55+/-4% and made the histamine inhibition fit better to the one-site model. Immepip (30 nM) induced a modest, but significant increase (113+/-2% of basal) in [(35)S]-GTPgammaS binding to synaptosomal membranes, an effect prevented by clobenpropit (1 microM) and by pre-treatment with pertussis toxin. In thalamus synaptosomes depolarisation-induced, Ca(2+)-dependent glutamate release was inhibited by histamine (1 microM, 25+/-4% inhibition) and immepip (30 nM, 38+/-5% reduction). These effects were reversed by clobenpropit (1microM). Conversely, immepip (up to 1 microM) had no effect on depolarisation-evoked [(3)H]-GABA release. Extracellular synaptic responses were recorded in the thalamus ventrobasal complex by stimulating corticothalamic afferents. H(3)R activation reduced by 38+/-7% the glutamate receptor-mediated field potentials (FPs), but increased the FP2/FP1 ratio (from 0.86+/-0.03 to 1.38+/-0.05) in a paired-pulse paradigm. Taken together, our results confirm the presence of H(3)Rs on thalamic nerve terminals and show that their activation modulates pre-synaptically glutamatergic, but not GABAergic neurotransmission.