Gut Microbiome Integration in Drug Discovery and Development of Small Molecules.

Human microbiomes, particularly in the gut, could have a major impact on the efficacy and toxicity of drugs. However, gut microbial metabolism is often neglected in the drug discovery and development process. Medicen, a Paris-based human health innovation cluster, has gathered more than 30 international leading experts from pharma, academia, biotech, clinical research organizations, and regulatory science to develop proposals to facilitate the integration of microbiome science into drug discovery and development. Seven subteams were formed to cover the complementary expertise areas of 1) pharma experience and case studies, 2) in silico microbiome-drug interaction, 3) in vitro microbial stability screening, 4) gut fermentation models, 5) animal models, 6) microbiome integration in clinical and regulatory aspects, and 7) microbiome ecosystems and models. Each expert team produced a state-of-the-art report of their respective field highlighting existing microbiome-related tools at every stage of drug discovery and development. The most critical limitations are the growing, but still limited, drug-microbiome interaction data to produce predictive models and the lack of agreed-upon standards despite recent progress. In this paper we will report on and share proposals covering 1) how microbiome tools can support moving a compound from drug discovery to clinical proof-of-concept studies and alert early on potential undesired properties stemming from microbiome-induced drug metabolism and 2) how microbiome data can be generated and integrated in pharmacokinetic models that are predictive of the human situation. Examples of drugs metabolized by the microbiome will be discussed in detail to support recommendations from the working group. SIGNIFICANCE STATEMENT: Gut microbial metabolism is often neglected in the drug discovery and development process despite growing evidence of drugs' efficacy and safety impacted by their interaction with the microbiome. This paper will detail existing microbiome-related tools covering every stage of drug discovery and development, current progress, and limitations, as well as recommendations to integrate them into the drug discovery and development process.

Widespread microplastic pollution in mangrove soils of Todos os Santos Bay, northern Brazil.

Microplastics have been studied in sediments from coastal and aquatic environments, but contamination of mangrove soils is still relatively unknown in most mangroves around the world. In this study, the presence of microplastics was investigated in six mangrove soils around the Todos Santos Bay (TSB), the largest and most important navigable bay on the Brazilian coast. Samples were collected at three depths (surface, 10 cm, and 30 cm) at three different distances from the lower tidal area. Ten grams of soil were sieved in a 150 µm mesh and centrifuged with ZnCl2 solution (density of 1.5 kg dm-3) for the extraction of microplastics. The microplastics were quantified, measured, and described using a systematic photographic method and the ImageJ program. Microplastics were abundant in all samples, with a mean of 10,782 ± 7,671 items kg-1 (max.: 31,087 items kg-1, only one sample <2,000 items kg-1), higher than any other value reported worldwide. The abundances varied among the six mangroves studied, with a predominance of fibers and mean size of 196 µm. Even remote mangroves were highly polluted, reflecting a large dispersion of the pollutants. The abundance did not differ significantly between soil depths, evidencing a continuous input and burial of microplastics in the soil up to 30 cm. The investigation of the source of microplastics and their presence in water and biota is urgent in this Brazilian region, and these results emphasize the need for global actions to protect coastal ecosystems.

Evolution of FMT - From early clinical to standardized treatments.

Faecal microbiota transplantation (FMT) is widely reported to be an effective treatment against recurrent Clostridioides difficile infections. Recent clinical studies support the therapeutic use of FMT for several other pathologies including inflammatory bowel disease, several types of cancer, and other functional or metabolic disorders. Initial guidelines are now available to overcome some of the technical and logistical issues for establishing a non-standardized treatment into clinical practice with proper safety and governance. To aid the improvement of guidance and standardization requirements for FMT, the International Alliance for Biological Standardization (IABS) and the BIOASTER Microbiology Technology Institute hosted a joint online workshop in May of 2021. The goal of the webinar was to provide a multi-disciplinary perspective of the ongoing efforts to develop FMT guidelines including technical, regulatory, and standardization requirements. Recognized experts gave insights into state-of-the art approaches and standards developed by international organizations and institutions.

Consistency of 3D femoral torsion measurement from MRI compared to CT gold standard.

BACKGROUND: Several hip and knee pathologies are associated with aberrant femoral torsion. Diagnostic workup includes computed tomography (CT) and magnetic resonance imaging (MRI). For three-dimensional (3D) analysis of complex deformities it would be desirable to measure femoral torsion from MRI data to avoid ionizing radiation of CT in a young patient population. 3D measurement of femoral torsion from MRI has not yet been compared to measurements from CT images. We hypothesize that agreement will exist between MRI and CT 3D measurements of femoral torsion. METHODS: CT and MRI data from 29 hips of 15 patients with routine diagnostic workup for suspected femoroacetabular impingement (FAI) were used to generate 3D bone models. 3D measurement of femoral torsion was performed by two independent readers using the method of Kim et al. which is validated for CT. Inter-modalitiy and inter-reader intraclass correlation coefficients (ICC) were calculated. RESULTS: Between MRI and CT 3D measurements an ICC of 0.950 (0.898; 0.976) (reader 1) respectively 0.950 (0.897; 0.976) (Reader 2) was found. The ICC (95% CI) expressing the inter-reader reliability for both modalities was 0.945 (0.886; 0.973) for MRI and 0.957 (0.910; 0.979) for CT, respectively. Mean difference between CT and MRI measurement was 0.42° (MRI - CT, SD: 2.77°, p = 0.253). CONCLUSIONS: There was consistency between 3D measurements of femoral torsion between computer rendered MRI images compared to measurements with the "gold standard" of CT images. ICC for inter-modality and inter-reader consistency indicate excellent reliability. Accurate, reliable and reproducible 3D measurement of femoral torsion is possible from MRI images.

Occult periprosthetic fractures of the acetabulum in THA using an elliptic cup design have no adverse impact on outcome.

Occult periprosthetic fractures have been defined as a fracture only visible on postoperative CT scans but not on postoperative plain radiography after an uneventful surgery without intraoperative fracture. The fracture rate for hemispherical and peripheral self-locking cups has been described as 8.4%. We retrospectively analyzed postoperative CT scans after primary THA to clear the question whether such occult periprosthetic fractures of the acetabulum require particular treatment strategy. Between 2014 and 2018 we identified 115 CT scans of 114 patients after primary cementless THA with elliptical cups using a direct anterior approach. The CT scans were obtained as part of other investigations. Localization of the fracture, patients demographics, clinical (WOMAC, Harris Hip Score) and radiological outcome were analyzed. Fracture and non-Fracture group were compared with regard to demographics and short-term outcome after 1 year. Four occult fractures (3.5%) were identified. Three fractures involved the posterior wall. All patients had an uneventful routine postoperative rehabilitation. Patients with occult fractures showed similar post- operative HHS and WOMAC scores at 3 (HHS p = 0.576, WOMAC p = 0.128) and 12 (HHS p = 0.479, WOMAC p = 0.588) months. There were no cup loosening nor radiolucent lines at latest follow-up (mean FU 22 months, range 12-34 months). Clinical and radiological short-term outcome was not impaired by the occurrence of an occult periprosthetic fracture of the acetabulum. The incidental detection of an occult periprosthetic fracture of the acetabulum does not seem to oblige the surgeon to adapt the postoperative regime.

Role of Health Information Technology in Addressing Health Disparities: Patient, Clinician, and System Perspectives.

Over the last decade, health information technology (IT) has dramatically transformed medical practice in the United States. On May 11-12, 2017, the National Institute on Minority Health and Health Disparities, in partnership with the National Science Foundation and the National Health IT Collaborative for the Underserved, convened a scientific workshop, "Addressing Health Disparities with Health Information Technology," with the goal of ensuring that future research guides potential health IT initiatives to address the needs of health disparities populations. The workshop examined patient, clinician, and system perspectives on the potential role of health IT in addressing health disparities. Attendees were asked to identify and discuss various health IT challenges that confront underserved communities and propose innovative strategies to address them, and to involve these communities in this process. Community engagement, cultural competency, and patient-centered care were highlighted as key to improving health equity, as well as to promoting scalable, sustainable, and effective health IT interventions. Participants noted the need for more research on how health IT can be used to evaluate and address the social determinants of health. Expanding public-private partnerships was emphasized, as was the importance of clinicians and IT developers partnering and using novel methods to learn how to improve health care decision-making. Finally, to advance health IT and promote health equity, it will be necessary to record and capture health disparity data using standardized terminology, and to continuously identify system-level deficiencies and biases.

Revision After Total Transmetatarsal Amputation.

Total transmetatarsal amputation (TMA) can be an option for foot salvage in gangrene, sepsis, or infected necrosis. However, the literature concerning predictive outcome factors and bacterial sampling is scarce. To identify potential associations between revision surgery and underlying bacteria or other preoperative selection criteria, we reviewed all patients with TMA who were treated at our institution. We compared the patients with remissions with surgical revisions. Among 96 adult patients with TMA (105 amputations), 42 required a revision surgery (40%), 18 had a further minor proximal surgical reamputation (17%) and 18 had a major proximal surgical reamputation (14%). In group comparisons, a previous infection with Staphylococcus aureus was protective with a lower revision risk (4/26 with revision surgery vs 22/26 without revisions; p = .03). This was the opposite for postoperative persistent soft tissue or bone infections (p < .01) and delayed wound healing (p < .01), which were positively associated with a revision risk. The American Society of Anesthesiologists Score, sex, age, body mass index, diabetes, polyneuropathy, chronic renal failure, dialysis, peripheral arterial disease, smoking status, and antibiotic regimen did not influence this revision risk. These results must be interpreted cautiously because no multiple variable calculations could be conducted as a result of the paucity of cases and confounding could not be evaluated sufficiently. TMA is an option to prevent major amputations, but it may be associated with a subsequent revision risk of 40% in adult patients. In our cohort study, persistent postamputation infection and delayed wound healing were associated with revision. However, no preoperative selection criteria were found that lead to revision surgery except for an infection with Staphylococcus aureus, which protected against revision surgery.

The clinical and genetic spectrum of catecholaminergic polymorphic ventricular tachycardia: findings from an international multicentre registry.

Aims: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an ion channelopathy characterized by ventricular arrhythmia during exertion or stress. Mutations in RYR2-coded Ryanodine Receptor-2 (RyR2) and CASQ2-coded Calsequestrin-2 (CASQ2) genes underlie CPVT1 and CPVT2, respectively. However, prognostic markers are scarce. We sought to better characterize the phenotypic and genotypic spectrum of CPVT, and utilize molecular modelling to help account for clinical phenotypes. Methods and results: This is a Pediatric and Congenital Electrophysiology Society multicentre, retrospective cohort study of CPVT patients diagnosed at <19 years of age and their first-degree relatives. Genetic testing was undertaken in 194 of 236 subjects (82%) during 3.5 (1.4-5.3) years of follow-up. The majority (60%) had RyR2-associated CPVT1. Variant locations were predicted based on a 3D structural model of RyR2. Specific residues appear to have key structural importance, supported by an association between cardiac arrest and mutations in the intersubunit interface of the N-terminus, and the S4-S5 linker and helices S5 and S6 of the RyR2 C-terminus. In approximately one quarter of symptomatic patients, cardiac events were precipitated by only normal wakeful activities. Conclusion: This large, multicentre study identifies contemporary challenges related to the diagnosis and prognostication of CPVT patients. Structural modelling of RyR2 can improve our understanding severe CPVT phenotypes. Wakeful rest, rather than exertion, often precipitated life-threatening cardiac events.

Cedratvirus lausannensis - digging into Pithoviridae diversity.

Amoeba-infecting viruses have raised scientists' interest due to their novel particle morphologies, their large genome size and their genomic content challenging previously established dogma. We report here the discovery and the characterization of Cedratvirus lausannensis, a novel member of the Megavirales, with a 0.75-1 µm long amphora-shaped particle closed by two striped plugs. Among numerous host cell types tested, the virus replicates only in Acanthamoeba castellanii leading to host cell lysis within 24 h. C. lausannensis was resistant to ethanol, hydrogen peroxide and heating treatments. Like 30 000-year-old Pithovirus sibericum, C. lausannensis enters by phagocytosis, releases its genetic content by fusion of the internal membrane with the inclusion membrane and replicates in intracytoplasmic viral factories. The genome encodes 643 proteins that confirmed the grouping of C. lausannensis with Cedratvirus A11 as phylogenetically distant members of the family Pithoviridae. The 575,161 bp AT-rich genome is essentially devoid of the numerous repeats harbored by Pithovirus, suggesting that these non-coding repetitions might be due to a selfish element rather than particular characteristics of the Pithoviridae family. The discovery of C. lausannensis confirms the contemporary worldwide distribution of Pithoviridae members and the characterization of its genome paves the way to better understand their evolution.

Development of a sandwich ELISA assay for quantification of human tissue transglutaminase in cell lysates and tissue homogenates.

Tissue transglutaminase (tTG) belongs to the multigene transglutaminase family of Ca2+-dependent protein cross-linking enzymes. There is a strong evidence that tTG is involved in pathology, such as neurodegenerative diseases, cancer, and celiac disease. To study physiopathological implication of tTG, a sandwich immunoassay has been developed with a new monoclonal antibody for the capture and polyclonal antibody both generated in house. Using this ready to use assay, the tTG protein level can be measured in human tissue homogenates and cells extracts easily in about 4 h. The limit of detection is 1.7 ng/ml; the coefficients of intra- and inter-assay variations range from 1 to 2 % and from 7 to 10 %, respectively. The assay is specific to tTG, and no cross reactivity with TG1, TG3, TG6, TG7, or factor XIIIa was observed. Finally, in the addition to the tTG activity assay previously developed, this assay should be a valuable tool to increase our knowledge of the tTG involvement in physiological and pathological states.

Analysis of Screening Electrocardiogram for the Subcutaneous Defibrillator in Adults with Congenital Heart Disease.

Candidates for the subcutaneous implantable cardioverter-defibrillator (S-ICD) are screened using an electrocardiogram (S-ECG) tool to measure appropriate detection. We sought to define the S-ICD candidacy of congenital heart disease patients using the S-ECG tool. We also analyzed the reliability of the (S-ECG) tool between measurers in this population. Patients above the age of 12 and with a diagnosis associated with either a higher incidence of cardiac arrest or vascular access challenges were asked to undergo screening. S-ECGs were then analyzed by a pediatric electrophysiologist, an S-ICD device engineer, and an S-ICD clinical representative for candidacy. Results were compared for interobserver variability and S-ECGs were analyzed by t test to determine variables that differ among passing and failing leads. Thirty-one patients underwent screening. Two of the 31 (6.5%) patients failed S-ICD screening. Analysis of the screening leads demonstrated the highest passing rates using lead III at a 5 mm/mV amplitude setting with 71 and 62% pass rate in the supine and standing positions, respectively. Interobserver analysis correlated well among the three measurers. There was a higher amplitude difference between QRS and T waves among passing versus failing S-ECG. Congenital heart disease patients have acceptable passage rates utilizing the S-ECG algorithm. Interobserver measurements were well correlated and these data suggest that the proximal coil to device (lead III) vector would be best utilized in this patient population. A larger difference between QRS and T wave amplitudes was associated with a higher S-ECG passing rate.

Morphological Study of the Encystment and Excystment of Vermamoeba vermiformis Revealed Original Traits.

Free-living amoebae are ubiquitous protozoa commonly found in water. Among them, Acanthamoeba and Vermamoeba (formerly Hartmannella) are the most represented genera. In case of stress, such as nutrient deprivation or osmotic stress, these amoebae initiate a differentiation process, named encystment. It leads to the cyst form, which is a resistant form enabling amoebae to survive in harsh conditions and resist disinfection treatments. Encystment has been thoroughly described in Acanthamoeba but poorly in Vermamoeba. Our study was aimed to follow the encystment/excystment processes by microscopic observations. We show that encystment is quite rapid, as mature cysts were obtained in 9 h, and that cyst wall is composed of two layers. A video shows that a locomotive form is likely involved in clustering cysts together during encystment. As for Acanthamoeba, autophagy is likely active during this process. Specific vesicles, possibly involved in ribophagy, were observed within the cytoplasm. Remarkably, mitochondria rearranged around the nucleus within the cyst, suggesting high needs in energy. Unlike Acanthamoeba and Naegleria, no ostioles were observed in the cyst wall suggesting that excystment is original. During excystment, large vesicles, likely filled with hydrolases, were found in close proximity to cyst wall and digest it. Trophozoite moves inside its cyst wall before exiting during excystment. In conclusion, Vermamoeba encystment/excystment displays original trends as compare to Acanthamoeba.

Moving towards universal prenatal detection of critical congenital heart disease in southern Nevada: a community-wide program.

This study compares the current, prenatal detection rate for critical congenital heart disease in Southern Nevada with the previously reported rate, after developing and expanding a comprehensive, community-wide fetal cardiology program. For the current-period analysis, we inquired our database and electronic health records for patients born in Clark County, Nevada, with critical congenital heart disease between May 2012 and April 2014, and we compared the results with the previous period between May 2003 and April 2006. The major components of the community-wide program include fetal congenital heart disease screening via general obstetric ultrasound studies performed in obstetrician's offices, radiology imaging centers, or maternal-fetal medicine specialty practices; subsequent referral for comprehensive fetal echocardiography performed in maternal-fetal medicine offices under the on-site supervision by fetal cardiologists; and recurring community educational programs teaching the 5-axial plane, fetal echocardiographic screening protocol to general obstetric sonographers and instructing perinatal sonographers in advanced imaging topics. For the current period, the prenatal detection rate for critical congenital heart disease in Southern Nevada was 71 versus 36% for the previous period (p < 0.001). The temporal improvement in prenatal detection of critical congenital heart disease may be related to our expanded decentralized, community-wide fetal cardiology program, and our experiences may be applicable to other metropolitan areas.

Encystment of Vermamoeba (Hartmannella) vermiformis: Effects of environmental conditions and cell concentration.

Vermamoeba vermiformis is a free-living amoeba (FLA) which is widely distributed in the environment. It is known to colonize water systems and to be a reservoir of pathogenic bacteria, such as Legionella pneumophila. For these reasons the control of V. vermiformis represents an important health issue. However, FLA may be resistant to disinfection treatments due to the process of encystment. Thereby, it is important to better understand factors influencing this process. In this aim, we investigated the effect of temperature, pH, osmotic pressure and cell concentration on the encystment of two V. vermiformis strains. Encystment was quite fast, with a 100% encystment rate being observed after 9h of incubation. For the two strains, an optimal encystment was obtained at 25 and 37°C. Concerning pH and osmotic pressure, there were different effects on the encystment according to the tested strains. For the reference strain (ATCC 50237), the patterns of encystment were similar for pH comprised between 5 and 9 and for KCl concentrations ranging from 0.05 to 0.2 mol L(-1). For the environmental strain (172A) an optimal encystment was obtained for basic pH (8 and 9) and for a concentration in KCl of 0.1 mol L(-1). The results also clearly demonstrated that the encystment rate increased with cell concentration, suggesting that there is an inter-amoebal communication. The present study establish for the first time environmental conditions favoring encystment and would lay the foundations to better control the encystment of V. vermiformis.

Attention deficit hyperactivity disorder screening electrocardiograms: a community-based perspective.

Screening electrocardiograms (EKGs) for attention deficit hyperactivity disorder (ADHD) medication administration is controversial. We reviewed our experience as a community-based cardiology group. We reviewed all ADHD screening EKGs during a 2-year period. We evaluated whether screening EKGs resulted in further consultation and if management was altered. We also evaluated differences between patients on ADHD medications and those starting ADHD medications and further stratified the patients into stimulant versus nonstimulant groups. A total of 691 screening EKGs met our criteria. Forty-two patients (6.1%) were recommended for further consultation. EKG findings requiring consultation included the following: left-ventricular hypertrophy, right atrial enlargement, arrhythmia, prolonged QT, and axis deviation. Studies performed during consultation included 39 echocardiograms, 2 stress tests, 2 Holter monitors, and 1 heart card. Five patients (0.72%) were identified to have cardiac disease, one of whom decided against starting ADHD medications due to an arrhythmia, resulting in a change in management (0.14%). Results comparing mean age, heart rate, and corrected QT interval between patients on medication and patients starting medications were as follows: 10.06 years, 82.87, bpm and 405.24 ms compared with 9.99 years, 80.05 bpm, and 405.82 ms, respectively (p = not significant [NS], p = 0.013 [NS], respectively). Results comparing mean age, heart rate, and corrected QT interval between patients on stimulant versus nonstimulant medications were as follows: 9.68 years, 83.10 bpm, and 403.04 ms compared with 9.81 years, 80.10 bpm, and 407.08 ms, respectively (p = NS for all). In our population, screening EKGs rarely resulted in management changes for patients taking or starting ADHD medications.

Psychobiotics and the Microbiota-Gut-Brain Axis: Where Do We Go from Here?

The bidirectional relationship between the gut microbiota and the nervous system is known as the microbiota-gut-brain axis (MGBA). The MGBA controls the complex interactions between the brain, the enteric nervous system, the gut-associated immune system, and the enteric neuroendocrine systems, regulating key physiological functions such as the immune response, sleep, emotions and mood, food intake, and intestinal functions. Psychobiotics are considered tools with the potential to modulate the MGBA through preventive, adjunctive, or curative approaches, but their specific mechanisms of action on many aspects of health are yet to be characterized. This narrative review and perspectives article highlights the key paradigms needing attention as the scope of potential probiotics applications in human health increases, with a growing body of evidence supporting their systemic beneficial effects. However, there are many limitations to overcome before establishing the extent to which we can incorporate probiotics in the management of neuropsychiatric disorders. Although this article uses the term probiotics in a general manner, it remains important to study probiotics at the strain level in most cases.

Radiation Oncology in the Philippines: Current State and Future Directions.

Purpose: As global cancer incidence continues to rise, low- to middle-income countries like the Philippines are projected to experience a disproportionate increase in cancer burden, further straining already limited resources. Radiation therapy (RT) is an essential and cost-effective modality in cancer care, both in the curative and palliative settings. In this article, we provide a brief narrative on the history of the field of radiation oncology in the Philippines and review the current challenges to effective and equitable RT service delivery in the country. Methods and Materials: We gathered data from the official websites of the Philippine government's health and statistics agencies, the Philippine Radiation Oncology Society, and the Directory of Radiotherapy Centers of the International Atomic Energy Agency, to review available human and infrastructure resources related to RT delivery in the country. Using the 6 health care dimensions of the World Health Organization's Building Blocks of Health Systems framework, we identified barriers to access and proposed possible initiatives for development. Results: Despite the remarkable growth of radiation oncology in the country in the past 2 decades, many challenges remain in the areas of human resources, infrastructure, policymaking, health economics, education, and service delivery. Radiation health workers and facilities are concentrated in the National Capital Region, limiting accessibility in rural areas. Out-of-pocket spending on RT-related expenditures remains high. The proper allocation of resources according to varying regional needs is impeded by the lack of a robust national cancer registry. Legislative reforms have been initiated but have yet to be fully implemented. Conclusions: Addressing these gaps in RT access will require in-depth study and multi-sectoral commitment aimed at establishing and implementing a nationwide framework for RT service delivery that can be readily adapted to varying regional needs. Despite many complex geographic, social, and economic obstacles, efforts by private and public sectors of society to provide ready access to RT services for all Filipinos continue to gain momentum.

Cooccurrence of free-living amoebae and nontuberculous Mycobacteria in hospital water networks, and preferential growth of Mycobacterium avium in Acanthamoeba lenticulata.

The incidence of lung and other diseases due to nontuberculous mycobacteria (NTM) is increasing. NTM sources include potable water, especially in households where NTM populate pipes, taps, and showerheads. NTM share habitats with free-living amoebae (FLA) and can grow in FLA as parasites or as endosymbionts. FLA containing NTM may form cysts that protect mycobacteria from disinfectants and antibiotics. We first assessed the presence of FLA and NTM in water and biofilm samples collected from a hospital, confirming the high prevalence of NTM and FLA in potable water systems, particularly in biofilms. Acanthamoeba spp. (genotype T4) were mainly recovered (8/17), followed by Hartmannella vermiformis (7/17) as well as one isolate closely related to the genus Flamella and one isolate only distantly related to previously described species. Concerning mycobacteria, Mycobacterium gordonae was the most frequently found isolate (9/17), followed by Mycobacterium peregrinum (4/17), Mycobacterium chelonae (2/17), Mycobacterium mucogenicum (1/17), and Mycobacterium avium (1/17). The propensity of Mycobacterium avium hospital isolate H87 and M. avium collection strain 104 to survive and replicate within various FLA was also evaluated, demonstrating survival of both strains in all amoebal species tested but high replication rates only in Acanthamoeba lenticulata. As A. lenticulata was frequently recovered from environmental samples, including drinking water samples, these results could have important consequences for the ecology of M. avium in drinking water networks and the epidemiology of disease due to this species.

Identification of human salivary transglutaminases.

Transglutaminases (TGs) expression and enzymatic activities in human saliva were investigated. Specific antibodies showed the co-existence of TG1, TG2, TG3 and TG4. TG2 and TG3 were found in native and multiple proteolytic forms. Our data indicate that TG1 and TG2 isoenzymes are highly active with the major activity attributed to TG1. These findings pave the way for future studies on the physiological role of TG in the oral cavity and the potential impact of their deregulation in TG-associated oral diseases.