ABSTRACT
In a previous study, we reported the in vitro potential probiotic and gamma-aminobutyric acid (GABA) production, of several strains from a collection of Lactiplantibacillus (Lpb) strains within the community of natural whey starters from the artisanal cheese industry. GABA is a non-protein amino acid widely distributed in nature and produced in animals, plants, and microorganisms. However, the best known role of GABA is its function as the major inhibitory neurotransmitter of the central nervous system. Preclinical and clinical evidence suggests that the GABAergic system has a relevant role in mental health disorders, such as anxiety and major depression. The modulation of the GABAergic system has been suggested as a potential strategy for treatment, one such mechanism of modulation is the influence of the microbiota-gut-brain axis through probiotic treatments. The present study was designed to investigate the in vivo probiotic potential of LPB145, a Lactiplantibacillus strain previously characterised as a GABA-producing potentially probiotic strain. Therefore, we evaluated the behavioural effects of chronic oral administration of LPB145 on rats' anxiety- and depression-like behaviours, using the elevated plus maze, open field, and the forced swimming test. The impact of LPB145 strain treatment on the gut microbiota structure and diversity was assessed to discern a possible mechanism of action of the LPB145 treatment through the microbiota-gut-brain axis. Our results showed that LPB145 administration induced an antidepressive-like behaviour without changes in locomotor activity. In contrast, the treatment did not modify the experimental anxiety. The structure and diversity of the intestinal microbiota remained unaffected by the treatment when compared to the control. However, specific clades that could be implicated in the behavioural changes did show differences in their relative abundance. These findings provide evidence regarding the potential of probiotic strains isolated from alimentary sources, to modulate the microbiota-gut-brain axis and positively impact mental health.
ABSTRACT
OBJECTIVES: Professional oral hygiene is essential to prevent peri-implant disease. Appropriate instruments should be employed for implant-supported restorations: they should effectively remove deposits without damaging dental implant surface. The aim of the present systematic review is to investigate the efficacy and safety of erythritol air-polishing in implant-supported rehabilitations, compared to alternative hygienic techniques. MATERIALS AND METHODS: The guidelines reported in the indications of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) were employed for this systematic review. The focused question was: 'what is the effect of erythritol air-polishing on dental implant surfaces regarding its cleansing efficacy and/or safety?' The final online search was conducted on 13 August 2023; MEDLINE-PubMed, Scopus and Cochrane Library were employed. Comparative in vitro or in vivo original studies were included. RESULTS: The initial database search yielded 128 entries; the final selection comprised 15 articles. The risk of bias was evaluated using the Newcastle Ottawa scale (NOS), the Cochrane Handbook for Systematic Reviews of Interventions, GRADE method. Ultrasonic scaling with PEEK tips, glycine air-polishing and cold atmospheric plasma were the devices most frequently compared to erythritol powder in the included studies. Erythritol air-polishing appeared to be significantly more effective in reducing biofilm compared to other treatments, without causing any significant damage to the implant surface and peri-implant tissues, promoting a good biological response. CONCLUSION: Erythritol air-polishing showed promising results for professional oral hygiene in implant-supported restorations. According to this systematic review, it is effective and safe for removing biofilm from titanium dental implants.
ABSTRACT
Honey bee colonies form a complex superorganism, with individual and social immune defences that control overall colony health. Sometimes these defences are not enough to overcome infections by parasites and pathogens. For that reason, several studies have been conducted to evaluate different strategies to improve honey bee health. A novel alternative that is being studied is the use of beneficial microbes. In a previous study, we isolated and characterised bacterial strains from the native gut microbiota of honey bees. Four Apilactobacillus kunkeei strains were mixed and administered in laboratory models to evaluate their potential beneficial effect on larvae and adult bees. This beneficial microbe mixture was safe; it did not affect the expression of immune-related genes, and it was able to decrease the mortality caused by Paenibacillus larvae infection in larvae and reduced the Nosema ceranae spore number in infected adult honey bees. In the present study, we aimed to delve into the impact of the administration of this beneficial microbe mixture on honey bee colonies, under field conditions. The mixture was administered in sugar syrup using lyophilised bacterial cells or fresh cultures, by aspersion or sprayed and feeder, once a week for three consecutive weeks, in autumn or spring 2015, 2017 and 2019. Colony strength parameters were estimated before the administration, and one and three months later. Simultaneously different samples were collected to evaluate the infection levels of parasites and pathogens. The results showed that administering the beneficial microbe mixture decreased or stabilised the infection by N. ceranae or Varroa destructor in some trials but not in others. However, it failed to improve the colony's strength parameters or honey production. Therefore, field studies can be a game-changer when beneficial microbes for honey bees are tested, and meticulous studies should be performed to test their effectiveness.
Subject(s)
Larva , Nosema , Bees/microbiology , Animals , Nosema/physiology , Larva/microbiology , Gastrointestinal Microbiome , Probiotics/pharmacology , Probiotics/administration & dosage , Honey , Paenibacillus larvaeABSTRACT
T cell therapy has become a new therapeutic opportunity against solid cancers. Predicting T cell behaviour and efficacy would help therapy optimization and clinical implementation. In this work, we model responsiveness of mouse prostate adenocarcinoma to T cell-based therapies. The mathematical model is based on a Cahn-Hilliard diffuse interface description of the tumour, coupled with Keller-Segel type equations describing immune components dynamics. The model is fed by pre-clinical magnetic resonance imaging data describing anatomical features of prostate adenocarcinoma developed in the context of the Transgenic Adenocarcinoma of the Mouse Prostate model. We perform computational simulations based on the finite element method to describe tumor growth dynamics in relation to local T cells concentrations. We report that when we include in the model the possibility to activate tumor-associated vessels and by that increase the number of T cells within the tumor mass, the model predicts higher therapeutic effects (tumor regression) shortly after therapy administration. The simulated results are found in agreement with reported experimental data. Thus, this diffuse-interface mathematical model well predicts T cell behavior in vivo and represents a proof-of-concept for the role such predictive strategies may play in optimization of immunotherapy against cancer.
Subject(s)
Adenocarcinoma , Cell- and Tissue-Based Therapy , Immunotherapy , Prostatic Neoplasms , T-Lymphocytes , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Animals , Disease Models, Animal , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Models, Theoretical , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapyABSTRACT
The microorganisms are found in the environment, forming sessile communities embedded in an extracellular matrix of their own production, called biofilm. These communities have a great relevance in the clinical context, since they are associated with infections caused by biofilm in medical implants, such as urinary catheters. The development of biofilms is a complex process where a great diversity of genes participate. The present work is based on the study of genes related to iron metabolism and its implication in the development of P. mirabilis biofilms and pathogenicity. For this study, two mutant strains defective in biofilm formation were selected, generated by the interruption of genes that encoded non-heme ferritin and TonB-dependent receptor. The mutations influence on the development of the biofilm was evaluated by different approaches. The complexity of the biofilm was analyzed using Confocal Laser Microscopy and image analysis. The mutants infectivity potential was assessed in two experimental mice models of urinary tract infection. The results obtained in the present work show us the role of the ferritin and a TonB-associated porin protein over the initial and later stages of biofilm development. Moreover, in the ascending UTI mouse model, both mutants failed to colonize the urinary tract. In CAUTI models, ferritin mutant damaged the bladder similarly to wild type but the Ton-B mutant was unable to generate infection in the urinary tract. The results obtained in the present work confirm the relevant role that iron metabolism genes have in P. mirabilis biofilm development and for infection in the urinary tract.
ABSTRACT
Neonatal calf diarrhoea is one of the challenges faced by intensive farming, and probiotics are considered a promising approach to improve calves' health. The objective of this study was to evaluate the effect of potential probiotic lactobacilli on new-born dairy calves' growth, diarrhoea incidence, faecal score, cytokine expression in blood cells, immunoglobulin A (IgA) levels in plasma and faeces, and pathogen abundance in faeces. Two in vivo assays were conducted at the same farm in two annual calving seasons. Treated calves received one daily dose of the selected lactobacilli (Lactobacillus reuteri TP1.3B or Lactobacillus johnsonii TP1.6) for 10 consecutive days. A faecal score was recorded daily, average daily gain (ADG) was calculated, and blood and faeces samples were collected. Pathogen abundance was analysed by absolute qPCR in faeces using primers directed at Salmonella enterica, rotavirus, coronavirus, Cryptosporidium parvum and three Escherichia coli virulence genes (eae, clpG and Stx1). The faecal score was positively affected by the administration of both lactobacilli strains, and diarrhoea incidence was significantly lower in treated calves. No differences were found regarding ADG, cytokine expression, IgA levels and pathogen abundance. Our findings showed that oral administration of these strains could improve gastrointestinal health, but results could vary depending on the calving season, which may be related to pathogen seasonality and other environmental effects.
Subject(s)
Cattle Diseases/therapy , Diarrhea , Lactobacillus johnsonii/metabolism , Limosilactobacillus reuteri/metabolism , Probiotics/therapeutic use , Animals , Animals, Newborn , Cattle , Cattle Diseases/microbiology , Cattle Diseases/prevention & control , Coronavirus Infections/prevention & control , Coronavirus Infections/veterinary , Cryptosporidiosis/prevention & control , Cytokines/blood , Dairying , Diarrhea/prevention & control , Diarrhea/therapy , Diarrhea/veterinary , Escherichia coli Infections/prevention & control , Escherichia coli Infections/veterinary , Feces/virology , Gastrointestinal Tract/microbiology , Immunoglobulin A/blood , Rotavirus Infections/prevention & control , Rotavirus Infections/veterinary , Salmonella Infections, Animal/prevention & controlABSTRACT
A global sensitivity analysis of a multiscale computational model of microvascular flow is presented. A total of 140 simulations have been completed and analyzed varying 6 input parameters and considering their effects on 7 output variables. Interestingly, the vascular network topology has been found as a determinant factor for both vasculature-related and interstitium-related quantities. Regarding the firsts, the vascular network topology has obtained a score of 5.5/6 and 6/6 for average and spatial distribution respectively (where 6 is the maximum and 1 is the minimum). On the other hand, considering interstitium-related quantities, the score is 4/6 and 5/6 for average and spatial distribution respectively. These results suggest that the network topology has a significant influence on the outcome of the computational analysis.
Subject(s)
Microcirculation/physiology , Microvessels/physiology , Models, Cardiovascular , Computer SimulationABSTRACT
Honeybees are important pollinators, having an essential role in the ecology of natural and agricultural environments. Honeybee colony losses episodes reported worldwide and have been associated with different pests and pathogens, pesticide exposure, and nutritional stress. This nutritional stress is related to the increase in monoculture areas which leads to a reduction of pollen availability and diversity. In this study, we examined whether nutritional stress affects honeybee gut microbiota, bee immunity, and infection by Nosema ceranae, under laboratory conditions. Consumption of Eucalyptus grandis pollen was used as a nutritionally poor-quality diet to study nutritional stress, in contraposition to the consumption of polyfloral pollen. Honeybees feed with Eucalyptus grandis pollen showed a lower abundance of Lactobacillus mellifer and Lactobacillus apis (Firm-4 and Firm-5, respectively) and Bifidobacterium spp. and a higher abundance of Bartonella apis, than honeybees fed with polyfloral pollen. Besides the impact of nutritional stress on honeybee microbiota, it also decreased the expression levels of vitellogenin and genes associated to immunity (glucose oxidase, hymenoptaecin and lysozyme). Finally, Eucalyptus grandis pollen favored the multiplication of Nosema ceranae. These results show that nutritional stress impacts the honeybee gut microbiota, having consequences on honeybee immunity and pathogen development. Those results may be useful to understand the influence of modern agriculture on honeybee health.
Subject(s)
Bees/immunology , Bees/microbiology , Gastrointestinal Microbiome , Immunity, Innate , Nosema/physiology , Animal Nutritional Physiological Phenomena/immunology , Animal Nutritional Physiological Phenomena/physiology , AnimalsABSTRACT
Feed withdrawal (FW) is a frequent issue in open outdoor feedlot systems, where unexpected circumstances can limit the animals' access to food. The relationship among fasting period, animal behaviour during feed reintroduction (FR) and acidosis occurrence has not been completely elucidated. Twenty steers fitted with rumen catheters were fed a high-concentrate diet (concentrate : forage ratio 85 : 15) and were challenged by a protocol of FW followed by FR. The animals were randomly assigned to one of the four treatments: FW for 12 h (T12), 24 h (T24), 36 h (T36) or no FW (control group) followed by FR. The steers' behaviour, ruminal chemistry, structure of the ruminal microbial community, blood enzymes and metabolites and ruminal acidosis status were assessed. Animal behaviour was affected by the FW-FR challenge ( P < 0.05). Steers from the T12, T24 and T36 treatments showed a higher ingestion rate and a lower frequency of rumination. Although all animals were suspected to have sub-acute ruminal acidosis (SARA) prior to treatment, a severe case of transient SARA arose after FR in the T12, T24 and T36 groups. The ruminal pH remained below the threshold adopted for SARA diagnosis ( pH value = 5.6) for more than three consecutive hours (24, 7 and 19 h in the T12, T24 and T36 treatments, respectively). The FW-FR challenge did not induce clinical acute ruminal acidosis even though steers from the T36 treatment presented ruminal pH values that were consistent with this metabolic disorder (pH threshold for acute acidosis = 5.2). Total mixed ration reintroduction after the withdrawal period reactivated ruminal fermentation as reflected by changes in the fermentation end-products. Ruminal lactic acid accumulation in steers from the T24 and T36 treatments probably led to the reduction of pH in these groups. Both the FW and the FR phases may have altered the structure of the ruminal microbiota community. Whereas fibrolytic bacterial groups decreased relative abundance in the restricted animals, both lactic acid producer and utiliser bacterial groups increased ( P < 0.05). The results demonstrated a synchronisation between Streptococcus (lactate producer) and Megasphaera (lactate utiliser), as the relative abundance of both groups increased, suggesting that bacterial resilience may be central for preventing the onset of metabolic disturbances such as ruminal acidosis. A long-FW period (36 h) produced rumen pH reductions well below and lactic acid concentration increased well above the accepted thresholds for acute acidosis without any perceptible clinical signs.
Subject(s)
Acidosis/veterinary , Animal Husbandry/methods , Cattle Diseases/physiopathology , Food Deprivation/physiology , Acidosis/etiology , Acidosis/physiopathology , Animal Feed , Animals , Blood Chemical Analysis/veterinary , Cattle/blood , Cattle Diseases/etiology , Diet/veterinary , Male , Random Allocation , Time FactorsABSTRACT
Honeybees Apis mellifera are important pollinators of wild plants and commercial crops. For more than a decade, high percentages of honeybee colony losses have been reported worldwide. Nutritional stress due to habitat depletion, infection by different pests and pathogens and pesticide exposure has been proposed as the major causes. In this study we analyzed how nutritional stress affects colony strength and health. Two groups of colonies were set in a Eucalyptus grandis plantation at the beginning of the flowering period (autumn), replicating a natural scenario with a nutritionally poor food source. While both groups of colonies had access to the pollen available in this plantation, one was supplemented with a polyfloral pollen patty during the entire flowering period. In the short-term, colonies under nutritional stress (which consumed mainly E. grandis pollen) showed higher infection level with Nosema spp. and lower brood and adult bee population, compared to supplemented colonies. On the other hand, these supplemented colonies showed higher infection level with RNA viruses although infection levels were low compared to countries were viral infections have negative impacts. Nutritional stress also had long-term colony effects, because bee population did not recover in spring, as in supplemented colonies did. In conclusion, nutritional stress and Nosema spp. infection had a severe impact on colony strength with consequences in both short and long-term.
Subject(s)
Animal Nutritional Physiological Phenomena/physiology , Bees/microbiology , Bees/physiology , Animals , Colony Collapse , Eucalyptus , Nosema , Pollen , Stress, Physiological , Trypanosomatina/genetics , Trypanosomatina/pathogenicity , Varroidae/pathogenicityABSTRACT
The use of native microorganisms with probiotic capacity is an alternative tool for the treatment and prevention of several diseases that affect animals, such as neonatal calf diarrhoea. The selection of probiotic strains within a collection is based on different in vitro and in vivo assays, which predict their potential. The aim of this study was to characterise a group of native Lactobacillus spp. strains isolated from faeces of healthy calves using an in vitro approach and to assess their ability to colonise the gastrointestinal tract (GIT) of calves. Native Lactobacillus spp. strains were evaluated on their capacity to survive low pH conditions and bile salts presence, biofilm formation and adhesion to both mucus and Caco-2 cells. Based on the in vitro characterisation, four strains (Lactobacillus johnsonii TP1.1, Lactobacillus reuteri TP1.3B, L. johnsonii TP1.6 and Lactobacillus amylovorus TP8.7) were selected to evaluate their capacity to colonise and persist in the GIT of calves. The assessment of enteric persistence involved an in vivo assay with oral administration of probiotics and quantification in faeces of the administered bacterial species with real-time quantitative PCR (qPCR). The study was conducted using 15 calves (1-month-old) which were divided into five groups of three animals, four of which were treated with four different selected strains and one was the control group. Strains TP1.3B and TP1.6 managed to persist in treated animals until ten days after the end of the administration period, indicating that they could be promising candidates for the design of probiotics for calves.
Subject(s)
Cattle Diseases/prevention & control , Cattle/microbiology , Gastrointestinal Diseases/veterinary , Gastrointestinal Tract/microbiology , Lactobacillus/physiology , Animals , Anti-Bacterial Agents/pharmacology , Bacterial Adhesion , Bile Acids and Salts/chemistry , Biofilms/growth & development , Caco-2 Cells , Cattle Diseases/microbiology , Cattle Diseases/therapy , Dairying , Feces/microbiology , Gastrointestinal Diseases/prevention & control , Gastrointestinal Diseases/therapy , Gastrointestinal Tract/metabolism , Humans , Hydrogen-Ion Concentration , Lactobacillus/classification , Lactobacillus/growth & development , Lactobacillus/isolation & purification , Probiotics/classification , Probiotics/isolation & purification , Probiotics/pharmacology , RNA, Ribosomal, 16S/geneticsABSTRACT
Due to their social behaviour, honey bees can be infected by a wide range of pathogens including the microsporidia Nosema ceranae and the bacteria Paenibacillus larvae. The use of probiotics as food additives for the control or prevention of infectious diseases is a widely used approach to improve human and animal health. In this work, we generated a mixture of four Lactobacillus kunkeei strains isolated from the gut microbial community of bees, and evaluated its potential beneficial effect on larvae and adult bees. Its administration in controlled laboratory models was safe for larvae and bees; it did not affect the expression of immune-related genes and it was able to decrease the mortality associated to P. larvae infection in larvae and the counts of N. ceranae spores from adult honey bees. These promising results suggest that this beneficial microorganism's mixture may be an attractive strategy to improve bee health. Field studies are being carried out to evaluate its effect in naturally infected colonies.
Subject(s)
Antibiosis , Bees/microbiology , Dietary Supplements , Lactobacillus/physiology , Probiotics , Animal Feed , Animals , Gastrointestinal Microbiome/physiology , Larva/growth & development , Nosema/physiology , Paenibacillus larvae/physiologyABSTRACT
In recent years, large-scale colony losses of honey bees (Apis mellifera) have been reported and the infection with the microsporidia Nosema ceranae has been involved. However, the effect of N. ceranae at the colony level and its role in colony losses vary in different geographic areas. This difference may be related to the presence of multiple N. ceranae genetic variants resulting in different biological consequences. In this study, we analyzed the genetic diversity of 75 N. ceranae samples obtained from 13 countries and Hawaii through inter-sequence single repetition (ISSR) and evaluated if two of these genetic variants triggered different immune responses when infecting Apis mellifera iberiensis. The genetic diversity analysis showed that 41% of the samples had the same DNA amplification pattern, including samples from most European countries except Spain, while the remaining samples showed high variability. Infection assays were performed to analyze the infection levels and the immune response of bees infected with N. ceranae from Spain and Uruguay. The infected bees presented similar infection levels, and both isolates downregulated the expression of abaecin, confirming the ability of the microsporidia to depress the immune response. Only N. ceranae from Uruguay downregulated the expression level of imd compared to control bees. On the other hand, both genetic variants triggered different expression levels of lysozyme. As imd and lysozyme play important roles in the response to pathogens, these results could reflect differences in the biological consequences of N. ceranae variants in A. mellifera infection.
Subject(s)
Bees/microbiology , Genetic Variation , Nosema/genetics , Nosema/pathogenicity , Animal Diseases/microbiology , Animals , Antimicrobial Cationic Peptides/genetics , Antimicrobial Cationic Peptides/metabolism , Bees/genetics , Bees/immunology , DNA, Fungal/chemistry , Down-Regulation , Gene Expression Regulation , Genes, Fungal/genetics , Geography , Insect Proteins/genetics , Insect Proteins/metabolism , Microsporidiosis/immunology , Microsporidiosis/veterinary , Muramidase/metabolism , Nosema/classification , RNA, Fungal/chemistry , Real-Time Polymerase Chain Reaction/methodsABSTRACT
Here, we report the genome sequence of Proteus mirabilis Pr2921, a uropathogenic bacterium that can cause severe complicated urinary tract infections. After gene annotation, we identified two additional copies of ucaA, one of the most studied fimbrial protein genes, and other fimbriae related-proteins that are not present in P. mirabilis HI4320.
ABSTRACT
We derive a sophisticated mathematical model for coupled heat and mass transport in the tumour microenvironment and we apply it to study nanoparticle delivery and hyperthermic treatment of cancer. The model has the unique ability of combining the following features: (i) realistic vasculature; (ii) coupled capillary and interstitial flow; (iii) coupled capillary and interstitial mass transfer applied to nanoparticles; and (iv) coupled capillary and interstitial heat transfer, which are the fundamental mechanisms governing nano-based hyperthermic treatment. This is an improvement with respect to previous modelling approaches, where the effect of blood perfusion on heat transfer is modelled in a spatially averaged form. We analyse the time evolution and the spatial distribution of particles and temperature in a tumour mass treated with superparamagnetic nanoparticles excited by an alternating magnetic field. By means of numerical experiments, we synthesize scaling laws that illustrate how nano-based hyperthermia depends on tumour size and vascularity. In particular, we identify two distinct mechanisms that regulate the distribution of particle and temperature, which are characterized by perfusion and diffusion, respectively.
ABSTRACT
A central therapeutic goal in many applications of modern Biomedicine is the reconstruction of the diseased arterial sections via robust and viable tissue equivalents. In-host remodelling is an emerging technology that exploits the remodelling ability of the host to regenerate tissue. We develop a general theoretical framework of growth and remodeling of arterial tissue starting from a synthetic, degradable, acellularized graft and we demonstrate the potential of mechanistic models to guide the development and assisting in the design of arterial tissue engineered constructs.
Subject(s)
Arteries/physiology , Models, Cardiovascular , Tissue Engineering/methods , Biomechanical Phenomena , Humans , Regeneration/physiologyABSTRACT
Starting from the fundamental laws of filtration and transport in biological tissues, we develop a computational model to capture the interplay between blood perfusion, fluid exchange with the interstitial volume, mass transport in the capillary bed, through the capillary walls and into the surrounding tissue. These phenomena are accounted at the microscale level, where capillaries and interstitial volume are viewed as two separate regions. The capillaries are described as a network of vessels carrying blood flow. We apply the model to study drug delivery to tumors. The model can be adapted to compare various treatment options. In particular, we consider delivery using drug bolus injection and nanoparticle injection into the blood stream. The computational approach is suitable for a systematic quantification of the treatment performance, enabling the analysis of interstitial drug concentration levels, metabolization rates and cell surviving fractions. Our study suggests that for the treatment based on bolus injection, the drug dose is not optimally delivered to the tumor interstitial volume. Using nanoparticles as intermediate drug carriers overrides the shortcomings of the previous delivery approach. This work shows that the proposed theoretical and computational framework represents a promising tool to compare the efficacy of different cancer treatments.
Subject(s)
Drug Carriers/chemistry , Models, Biological , Neoplasms/physiopathology , Algorithms , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Capillaries/physiology , Humans , Microcirculation , Nanoparticles/chemistry , Neoplasms/drug therapy , Oxygen/chemistry , Oxygen/metabolism , Shear Strength , Tirapazamine , Triazines/administration & dosage , Triazines/chemistryABSTRACT
The convulsant effects of α-thujone are attributed to inhibitory actions on the GABAA receptor. We investigated, for the first time, the effects of α-thujone or ß-thujone administrated centrally on the fear/anxiety behaviour of 3-day-old chicks in an Open Field and their modulation on the GABAA receptor. Higher doses were convulsant by eliciting a toxic and excitatory action, with the results showing that a dose of 78 nmol of either of the two diastereoisomers had an anxiogenic-like effect observed as an increased latency to ambulate and a reduced locomotor activity in an Open Field. Nevertheless, only the central administration of α-thujone reversed the increase induced by acute stress in the flunitrazepam-sensitive GABAA receptor recruitment. These findings demonstrated that α-thujone, when intracerebroventricularly administered, suppressed the GABAA receptor recruitment induced by acute stress, maybe due to α-thujone blocking the benzodiazepine binding site or another site of the GABAA complex. However, it should not be discarded that acute stress associated with novelty may have induced the recruitment of a subpopulation of GABAA receptors more sensitive to α-thujone than to the constitutive receptors, or that this monoterpene could have inhibited any protein or enzyme trafficking that modulated the phosphorylation of the receptor involved in the turnover of GABAA receptor. ß-Thujone showed behavioural effects similar to its diastereoisomer α-thujone. However, its action mechanism may have been mediated by other neurotransmitter systems, such as the serotonergic one or by a different biological effectiveness due to a distinct stereochemistry at the specific site of the GABAA receptor.
Subject(s)
Anxiety/chemically induced , Fear/drug effects , Monoterpenes/toxicity , Receptors, GABA-A/physiology , Animals , Animals, Newborn , Anti-Anxiety Agents/pharmacology , Bicyclic Monoterpenes , Chickens , Female , Flunitrazepam/pharmacology , GABA Modulators/pharmacology , Infusions, Intraventricular , Male , Monoterpenes/administration & dosage , Motor Activity/drug effects , Receptors, GABA-A/drug effectsABSTRACT
Computational models are used to study the combined effect of biomechanical and biochemical factors on coronary in-stent restenosis, which is a postoperative remodeling and regrowth pathology of the stented arteries. More precisely, we address numerical simulations, on the basis of Navier-Stokes and mass transport equations, to study the role of perturbed wall shear stresses and reduced oxygen concentration in a geometrical model reconstructed from a real porcine artery treated with a stent. Joining in vivo and in silico tools of investigation has multiple benefits in this case. On one hand, the geometry of the arterial wall and of the stent closely correspond to a real implanted configuration. On the other hand, the inspection of histological tissue samples informs us on the location and intensity of in-stent restenosis. As a result, we are able to correlate geometrical factors, such as the axial variation of the artery diameter and its curvature; the numerical quantification of biochemical stimuli, such as wall shear stresses; and the availability of oxygen to the inner layers of the artery, with the appearance of in-stent restenosis. This study shows that the perturbation of the vessel curvature could induce hemodynamic conditions that stimulate undesired arterial remodeling.
Subject(s)
Coronary Restenosis/metabolism , Models, Cardiovascular , Oxygen/metabolism , Animals , Computer Simulation , Hemodynamics/physiology , Percutaneous Coronary Intervention , Stents , SwineABSTRACT
In this paper, we discuss a technique for weakly enforcing flow rate conditions in computational hemodynamics. In particular, we study the effectiveness of cutting lateral branches from the computational domain and replacing them with non-perturbing boundary conditions to simplify the geometrical reconstruction and the numerical simulation. All these features are investigated both in the case of rigid and compliant walls. Several numerical results are presented to discuss the reliability of the proposed method.