TREM-2: friend or foe in infectious diseases?

The triggering receptor expressed on myeloid cells-2 (TREM-2) is an immune receptor expressed on immune and non-immune cells, more frequently investigated in neurodegenerative disorders and considered a marker for microglia activation. In infectious diseases, the receptor was initially believed to be an anti-inflammatory molecule, opposing the inflammation triggered by TREM-1. Currently, TREM-2 is associated with different aspects in response to infectious stimuli, including the induction of bacterial phagocytosis and clearance, containment of exacerbated pro-inflammatory responses, induction of M2 differentiation and activation of Th1 lymphocytes, besides of neurological damage after viral infection. Here, we present and discuss results published in the last two decades regarding the expression, activation and functions of TREM-2 during the course of bacterial, viral, fungal and parasitic infections. A surprisingly plasticity was observed regarding the roles of the receptor in the aforementioned contexts, which largely varied according to the cell/organ and pathogen type, besides influencing disease outcome. Therefore, our review aimed to critically overview the role of TREM-2 in infectious diseases, highlighting its potential to be used as a clinical biomarker or therapeutic target.

Effectiveness of interdental cleaning devices with active substances: a systematic review.

OBJECTIVES: To systematically review the literature on the efficacy of interdental cleaning devices (ICDs) used with active substances, as adjuncts to toothbrushing, in comparison with toothbrushing alone or with ICDs without active substances. MATERIALS AND METHODS: Searches for randomized clinical trials were performed in PubMed, Embase, Scopus, Cochrane (CENTRAL), and Web of Science. Two independent researchers performed study selection, data extraction, and risk-of-bias assessment; a third one resolved any disagreement. Meta-analysis was not feasible, and a narrative approach was used to synthesize the evidence. RESULTS: Seven studies were included. Dental floss with chlorhexidine was used in five studies, whereas interdental brushes with chlorhexidine and cetylpyridinium chloride were used in one study each. ICDs with active substances resulted in significantly higher antiplaque and antigingivitis efficacies than without ICDs (n = 3). ICDs with and without active substances demonstrated contrasting results. For this comparison, six studies were included for each outcome. Significantly higher antigingivitis efficacy of ICDs with active substances was noted in four studies, whereas significantly higher antiplaque efficacy of ICDs with active substances was reported in three studies. All comparisons demonstrated a very low certainty of evidence. CONCLUSIONS: There is no robust evidence for the additional clinical efficacy of ICDs with active substances regarding their antiplaque and antigingivitis efficacies. These devices may have additional clinical efficacy when compared with the absence of interproximal hygiene. CLINICAL RELEVANCE: The use of ICDs helps maintain or achieve periodontal health. However, the adjunct use of active substances may not provide additional benefits.

Structural Computational Analysis of the Natural History of Class I aminoacyl-tRNA Synthetases Suggests their Role in Establishing the Genetic Code.

The evolutionary history of Class I aminoacyl-tRNA synthetases (aaRS) through the reconstruction of ancestral sequences is presented. From structural molecular modeling, we sought to understand its relationship with the acceptor arms and the tRNA anticodon loop, how this relationship was established, and the possible implications in determining the genetic code and the translation system. The results of the molecular docking showed that in 7 out 9 aaRS, the acceptor arm and the anticodon loop bond practically in the same region. Domain accretion process in aaRS and repositioning of interactions between tRNAs and aaRS are illustrated. Based on these results, we propose that the operational code and the anticodon code coexisted, competing for the aaRS catalytic region, while consequently contributed to the stabilization of these proteins.

TREM-1 isoforms in bacterial infections: to immune modulation and beyond.

The triggering receptor expressed on myeloid cells 1 (TREM-1) is an innate immunity receptor associated with the amplification of inflammation in sterile and non-sterile inflammatory disorders. Since its first description, the two isoforms of the receptor, membrane and soluble (mTREM-1 and sTREM-1, respectively) have been largely explored in the immunopathogenesis of several bacterial diseases and sepsis. The role of the receptor in these scenarios seems to be at least partly dependent on the source/type of bacteria, host and context. As uncontrolled inflammation is a result of several bacterial infections, the inhibition of the receptor has been considered as a promising approach to treat such conditions. Further, sTREM-1 has been explored as a biomarker for diagnosis and/or prognosis of several bacterial diseases. Therefore, this review aims to provide an updated insight into how the receptor influences and is influenced by bacterial infections, highlighting the advances regarding the use/manipulation of TREM-1 isoforms in biomedical research and clinical practice.

The Lisbon Agreement on femoroacetabular impingement imaging-part 2: general issues, parameters, and reporting.

OBJECTIVES: Imaging assessment for the clinical management of femoroacetabular impingement (FAI) is controversial because of a paucity of evidence-based guidance and notable variability among practitioners. Hence, expert consensus is needed because standardised imaging assessment is critical for clinical practice and research. We aimed to establish expert-based statements on FAI imaging by using formal methods of consensus building. METHODS: The Delphi method was used to formally derive consensus among 30 panel members from 13 countries. Forty-four questions were agreed upon, and relevant seminal literature was circulated and classified in major topics to produce answering statements. The level of evidence was noted for all statements, and panel members were asked to score their level of agreement (0-10). This is the second part of a three-part consensus series and focuses on 'General issues' and 'Parameters and reporting'. RESULTS: Forty-seven statements were generated and group consensus was reached for 45. Twenty-five statements pertaining to 'General issues' (9 addressing diagnosis, differential diagnosis, and postoperative imaging) and 'Parameters and reporting' (16 addressing femoral/acetabular parameters) were produced. CONCLUSIONS: The available evidence was reviewed critically, recommended criteria for diagnostic imaging highlighted, and the roles/values of different imaging parameters assessed. Radiographic evaluation (AP pelvis and a Dunn 45° view) is the cornerstone of hip-imaging assessment and the minimum imaging study that should be performed when evaluating adult patients for FAI. In most cases, cross-sectional imaging is warranted because MRI is the 'gold standard' imaging modality for the comprehensive evaluation, differential diagnosis assessment, and FAI surgical planning. KEY POINTS: • Diagnostic imaging for FAI is not standardised due to scarce evidence-based guidance on which imaging modalities and diagnostic criteria/parameters should be used. • Radiographic evaluation is the cornerstone of hip assessment and the minimum study that should be performed when assessing suspected FAI. Cross-sectional imaging is justified in most cases because MRI is the 'gold standard' modality for comprehensive FAI evaluation. • For acetabular morphology, coverage (Wiberg's angle and acetabular index) and version (crossover, posterior wall, and ischial spine signs) should be assessed routinely. On the femoral side, the head-neck junction morphology (α° and offset), neck morphology (NSA), and torsion should be assessed.

The Lisbon Agreement on Femoroacetabular Impingement Imaging-part 3: imaging techniques.

OBJECTIVES: Imaging diagnosis of femoroacetabular impingement (FAI) remains controversial due to a lack of high-level evidence, leading to significant variability in patient management. Optimizing protocols and technical details is essential in FAI imaging, although challenging in clinical practice. The purpose of this agreement is to establish expert-based statements on FAI imaging, using formal consensus techniques driven by relevant literature review. Recommendations on the selection and use of imaging techniques for FAI assessment, as well as guidance on relevant radiographic and MRI classifications, are provided. METHODS: The Delphi method was used to assess agreement and derive consensus among 30 panel members (musculoskeletal radiologists and orthopedic surgeons). Forty-four questions were agreed on and classified into five major topics and recent relevant literature was circulated, in order to produce answering statements. The level of evidence was assessed for all statements and panel members scored their level of agreement with each statement during 4 Delphi rounds. Either "group consensus," "group agreement," or "no agreement" was achieved. RESULTS: Forty-seven statements were generated and group consensus was reached for 45. Twenty-two statements pertaining to "Imaging techniques" were generated. Eight statements on "Radiographic assessment" and 12 statements on "MRI evaluation" gained consensus. No agreement was reached for the 2 "Ultrasound" related statements. CONCLUSION: The first international consensus on FAI imaging was developed. Researchers and clinicians working with FAI and hip-related pain may use these recommendations to guide, develop, and implement comprehensive, evidence-based imaging protocols and classifications. KEY POINTS: • Radiographic evaluation is recommended for the initial assessment of FAI, while MRI with a dedicated protocol is the gold standard imaging technique for the comprehensive evaluation of this condition. • The MRI protocol for FAI evaluation should include unilateral small FOV with radial imaging, femoral torsion assessment, and a fluid sensitive sequence covering the whole pelvis. • The definite role of other imaging methods in FAI, such as ultrasound or CT, is still not well defined.

Hip arthroscopy with initial access to the peripheral compartment provides significant improvement in FAI patients.

PURPOSE: This study was designed to evaluate the clinical and radiographic results of arthroscopic treatment of femoroacetabular impingement (FAI) using the technique of initial access to the peripheral compartment. It is based on a single surgeon large case series with a minimum of 2 years follow-up. METHODS: Prospective longitudinal study with consecutive patients. Inclusion criteria were the presence of FAI syndrome that had failed non-operative treatment and had a hip arthroscopy with initial access to the peripheral compartment. Exclusion criteria were previous hip surgery, patients younger than 16 or older than 60 years, Tönnis grade ≥ 2 osteoarthritis, hip dysplasia based on radiographic evidence of LCEA less than 25° and workers compensation cases. One hundred and sixty hips met the inclusion criteria, 84 were female and 70 were male patients (six bilateral cases), with a median age of 36 years (range 16-59). RESULTS: The median alpha angle correction was 22.6º (range 5.9-46.7) (p < 0.01) and the average LCEA correction when acetabuloplasty was undertaken was 6.5º (range - 1.4-20.8) (p < 0.01). The mean NAHS at baseline was 56.1 (range 16-96) and improved to 83.2 at the last follow up (range 44-100) for the patients that had no additional procedure (p < 0.01). The mean average improvement was 27.7º points (range - 16-73). No iatrogenic labral perforation and no full-thickness chondral damage were recorded during the arthroscopic procedures. CONCLUSIONS: Favourable outcomes are reported for the arthroscopic treatment of FAI with initial access to the peripheral compartment. The technique is protective against iatrogenic chondral and labral damage, more conservative to the joint capsule, but the mean traction time was relatively long when suture anchors were used. The results are comparable to the classic initial central compartment approach. LEVEL OF EVIDENCE: Level IV.

The role of the triggering receptor expressed on myeloid cells-1 (TREM-1) in non-bacterial infections.

The triggering receptor expressed on myeloid cells 1 (TREM-1) is a receptor of the innate immune system, expressed mostly by myeloid cells and primarily associated with pro- inflammatory responses. Although the exact nature of its ligands has not yet been fully elucidated, many microorganisms or danger signals have been proposed as inducers of its activation or the secretion of sTREM-1, the soluble form with putative anti-inflammatory effects. In the course of the 20 years since its first description, several studies have investigated the involvement of TREM-1 in bacterial infections. However, the number of studies describing the role of TREM-1 in fungal, viral and parasite-associated infections has only increased in the last few years, showing a diverse contribution of the receptor in these scenarios, with beneficial or detrimental activities depending on the context. Therefore, this review aims to discuss how TREM-1 may influence viral, fungal and parasitic infection outcomes, highlighting its potential as a therapeutic target and biomarker for diagnosis and prognosis of non-bacterial infectious diseases.

Correction to: The Lisbon Agreement on Femoroacetabular Impingement Imaging-part 1: overview.

The original version of this article, published on 14 May 2020, unfortunately contained a mistake.

The Lisbon Agreement on Femoroacetabular Impingement Imaging-part 1: overview.

OBJECTIVES: Imaging assessment for the clinical management of femoroacetabular impingement (FAI) syndrome remains controversial because of a paucity of evidence-based guidance and notable variability in clinical practice, ultimately requiring expert consensus. The purpose of this agreement is to establish expert-based statements on FAI imaging, using formal techniques of consensus building. METHODS: A validated Delphi method and peer-reviewed literature were used to formally derive consensus among 30 panel members (21 musculoskeletal radiologists and 9 orthopaedic surgeons) from 13 countries. Forty-four questions were agreed on, and recent relevant seminal literature was circulated and classified in five major topics ('General issues', 'Parameters and reporting', 'Radiographic assessment', 'MRI' and 'Ultrasound') in order to produce answering statements. The level of evidence was noted for all statements, and panel members were asked to score their level of agreement with each statement (0 to 10) during iterative rounds. Either 'consensus', 'agreement' or 'no agreement' was achieved. RESULTS: Forty-seven statements were generated, and group consensus was reached for 45 (95.7%). Seventeen of these statements were selected as most important for dissemination in advance. There was no agreement for the two statements pertaining to 'Ultrasound'. CONCLUSION: Radiographic evaluation is the cornerstone of hip evaluation. An anteroposterior pelvis radiograph and a Dunn 45° view are recommended for the initial assessment of FAI although MRI with a dedicated protocol is the gold standard imaging technique in this setting. The resulting consensus can serve as a tool to reduce variability in clinical practices and guide further research for the clinical management of FAI. KEY POINTS: • FAI imaging literature is extensive although often of low level of evidence. • Radiographic evaluation with a reproducible technique is the cornerstone of hip imaging assessment. • MRI with a dedicated protocol is the gold standard imaging technique for FAI assessment.

Femoroacetabular Impingement: What the Surgeon Wants to Know.

Femoroacetabular impingement (FAI) is increasingly recognized as a risk factor for early hip degeneration in young active patients. The diagnosis depends on clinical examination and proper imaging that should be able to identify abnormal and sometimes subtle morphological changes. Labral tears and cartilage lesions rarely occur without underlying bone abnormalities. Surgical approaches to treat FAI are increasing significantly worldwide, even without a clearly defined consensus of what should be accepted as the standard imaging diagnosis for FAI morphology.Hip abnormalities encompass many variations related to the shape, size, and spatial orientation of both sides of the joint and can be difficult to characterize if adequate imaging is not available.This article presents a comprehensive review about the information orthopaedic surgeons need to know from radiologists to plan the most rational approach to a painful hip resulting from a mechanical abnormality.

Hip shape is symmetric, non-dependent on limb dominance and gender-specific: implications for femoroacetabular impingement. A 3D CT analysis in asymptomatic subjects.

OBJECTIVE: To determine the reference intervals (RefInt) of the quantitative morphometric parameters of femoroacetabular impingement (FAI) in asymptomatic hips with computed tomography (CT) and determine their dependence on age, side, limb dominance and sex. METHODS: We prospectively included 590 patients and evaluated 1111 hips with semi-automated CT analysis. We calculated overall, side- and sex-specific parameters for imaging signs of cam [omega and alpha angle (α°)] and pincer-type morphology [acetabular version (ACvers), lateral centre-edge angle (LCEA) and cranio-caudal coverage]. RESULTS: Hip shape was symmetrical and did not depend on limb dominance. The 95% RefInt limits were sex-different for all cam-type parameters and extended beyond current abnormal thresholds. Specifically, the upper limits of RefInt for α° at 12:00, 1:30 and 3:00 o'clock positions were 56°, 70° and 58°, respectively, and 45° for LCEA. Acetabular morphology varied between age groups, with a trend toward an LCEA/ACvers increase over time. CONCLUSION: Our morphometric measurements can be used to estimate normal hip morphology in asymptomatic individuals. Notably they extended beyond current thresholds used for FAI imaging diagnosis, which was most pronounced for cam-type parameters. We suggest the need to reassess α° RefInt and consider a 60° threshold for the 12:00/3:00 positions and 65-70° for other antero-superior positions. KEY POINTS: • Hip shape is symmetrical regardless of limb dominance. • Pincer/cam morphology is frequent in asymptomatic subjects (20 and 71%, respectively). • LCEA and acetabular version increases with age (5-7° between opposite age groups). • Femoral morphology is stable after physeal closure (in the absence of pathology). • Alpha and omega angle thresholds should be set according to sex.

Cam deformity and the omega angle, a novel quantitative measurement of femoral head-neck morphology: a 3D CT gender analysis in asymptomatic subjects.

OBJECTIVE: Our objectives were to use 3D computed tomography (CT) to define head-neck morphologic gender-specific and normative parameters in asymptomatic individuals and use the omega angle (Ω°) to provide quantification data on the location and radial extension of a cam deformity. METHODS: We prospectively included 350 individuals and evaluated 188 asymptomatic hips that underwent semiautomated CT analysis. Different thresholds of alpha angle (α°) were considered in order to analyze cam morphology and determine Ω°. We calculated overall and gender-specific parameters for imaging signs of cam morphology (Ω° and circumferential α°). RESULTS: The 95 % reference interval limits were beyond abnormal thresholds found in the literature for cam morphology. Specifically, α° at 3/1 o´clock were 46.9°/60.8° overall, 51.8°/65.4° for men and 45.7°/55.3° for women. Cam prevalence, magnitude, location, and epicenter were significantly gender different. Increasing α° correlated with higher Ω°, meaning that higher angles correspond to larger cam deformities. CONCLUSION: Hip morphometry measurements in this cohort of asymptomatic individuals extended beyond current thresholds used for the clinical diagnosis of cam deformity, and α° was found to vary both by gender and measurement location. These results suggest that α° measurement is insufficient for the diagnosis of cam deformity. Enhanced morphometric evaluation, including 3D imaging and Ω°, may enable a more accurate diagnosis. KEY POINTS: • 95% reference interval limits of cam morphotype were beyond currently defined thresholds. • Current morphometric definitions for cam-type morphotype should be applied with care. • Cam prevalence, magnitude, location, and epicenter are significantly gender different. • Cam and alpha angle thresholds should be defined according to sex/location. • Quantitative 3D morphometric assessment allows thorough and reproducible FAI diagnosis and monitoring.

Intravital Microscopy Evidence That Methylene Blue Should Be a Vasopressor-Sparing Agent in Sepsis Vasoplegia.

Microvasculature failure is expected in sepsis and at higher amine concentrations. Therefore, special attention focused individually on microcirculation is needed. Here, we present that methylene blue can prevent leukocytes from adhering to the endothelium in a rat model of lipopolysaccharide-induced endotoxemia. As hypothesis evidence, an intravital microscopy image is presented.

Association between oral health-related quality of life and symptoms of temporomandibular disorder among older adults: A cross-sectional study.

OBJECTIVE: Evaluate the association between oral health-related quality of life (OHRQoL) and self-reported symptoms of TMD. METHODS: Representative samples of older adults (≥60 years) were included (n = 569). Both TMD symptoms and OHRQoL were assessed by Fonseca Anamnestic Index (FAI) and Oral Health Impact Profile-14 (OHIP-14), respectively. Prevalence (those answering "frequently" or "always" in at least one question), severity (total means scores), and extent (number of questions answered as "frequently" or "always") of OHRQoL were estimated. RESULTS: Overall, 33.4% and 9.5% had mild or moderate/severe TMD symptoms. Those with any symptom of TMD had a prevalence ratio (PR) 38% higher for the worst OHRQoL (95% confidence interval [95%CI]:1.04-1.82) compared to those without TMD symptoms. Worst OHRQoL were observed for those with mild (PR:1.35; 95%CI:1.01-1.81) and moderate/severe TMD (PR:1.53; 95%CI:1.04-2.26). Similar results were detected in the severity and extent of OHRQoL. CONCLUSION: Severity TMD was associated with worse ORHQoL.

Differential epitope prediction across diverse circulating variants of SARS-COV-2 in Brazil.

COVID-19, caused by the SARS-COV-2 virus, induces numerous immunological reactions linked to the severity of the clinical condition of those infected. The surface Spike protein (S protein) present in Sars-CoV-2 is responsible for the infection of host cells. This protein presents a high rate of mutations, which can increase virus transmissibility, infectivity, and immune evasion. Therefore, we propose to evaluate, using immunoinformatic techniques, the predicted epitopes for the S protein of seven variants of Sars-CoV-2. MHC class I and II epitopes were predicted and further assessed for their immunogenicity, interferon-gamma (IFN-γ) inducing capacity, and antigenicity. For B cells, linear and structural epitopes were predicted. For class I MHC epitopes, 40 epitopes were found for the clades of Wuhan, Clade 2, Clade 3, and 20AEU.1, Gamma, and Delta, in addition to 38 epitopes for Alpha and 44 for Omicron. For MHC II, there were differentially predicted epitopes for all variants and eight equally predicted epitopes. These were evaluated for differences in the MHC II alleles to which they would bind. Regarding B cell epitopes, 16 were found in the Wuhan variant, 14 in 22AEU.1 and in Clade 3, 15 in Clade 2, 11 in Alpha and Delta, 13 in Gamma, and 9 in Omicron. When compared, there was a reduction in the number of predicted epitopes concerning the Spike protein, mainly in the Delta and Omicron variants. These findings corroborate the need for updates seen today in bivalent mRNA vaccines against COVID-19 to promote a targeted immune response to the main circulating variant, Omicron, leading to more robust protection against this virus and avoiding cases of reinfection. When analyzing the specific epitopes for the RBD region of the spike protein, the Omicron variant did not present a B lymphocyte epitope from position 390, whereas the epitope at position 493 for MHC was predicted only for the Alpha, Gamma, and Omicron variants.

Modified triangular osteosynthesis in the treatment of bilateral sacroiliac joint dislocation.

Bilateral sacroiliac joint dislocation is a rare injury associated with rotational and vertical instability of the pelvic ring. The ideal strategy for the reduction and fixation of this injury is poorly described in the current literature. Triangular osteosynthesis provides multiplanar stability to the posterior pelvic ring allowing early weight bearing. We present the case of a young female with a bilateral sacroiliac joint dislocation who underwent a modified bilateral triangular osteosynthesis, using S1 pedicle screws to improve the reduction of the sacroiliac joint.

Poor Quality of Sleep is Associated with Lower Academic Performance in Undergraduate Dental Students: A Cross-Sectional Study.

Purpose: This study aimed to assess the quality of sleep and associated factors among dental students. Methods: All dental students regularly enrolled at the Federal University of Pelotas, Brazil, were invited to participate. A structured online questionnaire was applied to collect the independent variables, including academic performance. Quality of sleep was assessed by the validated version of the Pittsburgh Sleep Quality Index. Sample was dichotomized as good sleep quality (total score: ≤ 4) and at least poor quality (total score: ≥ 5). Adjusted analyses were performed using Poisson regression with robust variance to detect the association between sleep quality and independent variables. Independent adjusted models were performed to the whole-sample, only undergraduate and only graduate dental students. Results: Poor quality of sleep was detected in 266 (65.2%) dental students, of which 228 (68.9%) and 38 (49.4%) were undergraduate and graduate dental students, respectively. Female students presented a prevalence ratio (PR) 19% higher compared to males (95% confidence interval [CI] 1.01-1.41). When only graduate students were considering, those that reported not being the head of the family presented a PR 4.39 higher for poor quality of sleep (95% CI 1.91-10.09). Poor quality of sleep was associated with lower academic performance among undergraduate students (PR: 0.94; 95% CI 0.89-0.99), but not significantly associated when graduate students are considered (PR: 0.99; 95% CI 0.96-1.03). Conclusion: It was concluded that dental students, mainly female ones, have high prevalence of poor quality of sleep, which is associated with undergraduate student's worst academic performance. Supplementary Information: The online version contains supplementary material available at 10.1007/s41782-022-00223-2.

Hip joint contact pressure and force: a scoping review of in vivo and cadaver studies.

Aims: Research on hip biomechanics has analyzed femoroacetabular contact pressures and forces in distinct hip conditions, with different procedures, and used diverse loading and testing conditions. The aim of this scoping review was to identify and summarize the available evidence in the literature for hip contact pressures and force in cadaver and in vivo studies, and how joint loading, labral status, and femoral and acetabular morphology can affect these biomechanical parameters. Methods: We used the PRISMA extension for scoping reviews for this literature search in three databases. After screening, 16 studies were included for the final analysis. Results: The studies assessed different hip conditions like labrum status, the biomechanical effect of the cam, femoral version, acetabular coverage, and the effect of rim trimming. The testing and loading conditions were also quite diverse, and this disparity limits direct comparisons between the different researches. With normal anatomy the mean contact pressures ranged from 1.54 to 4.4 MPa, and the average peak contact pressures ranged from 2 to 9.3 MPa. Labral tear or resection showed an increase in contact pressures that diminished after repair or reconstruction of the labrum. Complete cam resection also decreased the contact pressure, and acetabular rim resection of 6 mm increased the contact pressure at the acetabular base. Conclusion: To date there is no standardized methodology to access hip contact biomechanics in hip arthroscopy, or with the preservation of the periarticular soft-tissues. A tendency towards improved biomechanics (lower contact pressures) was seen with labral repair and reconstruction techniques as well as with cam correction.

Effects of histamine on the contractility of the rat distal cauda epididymis.

The motor activity of the epididymis duct is an essential process for male fertility and it is regulated by hormonal, neuronal and epithelial mechanisms. However, although there is evidence for the presence of histamine in the epididymis, its effects on epididymal motor activity are unknown. This study sought to evaluate the contractile effects of histamine on the rat distal cauda epididymis duct. Segments of the distal cauda epididymis duct from male Wistar rats were isolated and used in isolated organ bath experiments to evaluate the contractile effects of histamine in the absence or presence of antagonists of histamine receptors, α1-adrenoceptors and muscarinic acetylcholine receptors. The effects of histamine on noradrenaline induced contractions were also investigated. Histamine was able to induce phasic contractions on rat distal cauda epididymis duct which were prevented by promethazine 10-1000 nM (H1 receptor antagonist), ranitidine 1-100 µM (H2 receptor antagonist), atropine 100 nM (muscarinic antagonist), and prazosin 100 nM (α1-adrenoceptor antagonist). In addition, histamine was also able to modify noradrenaline-induced contractions possibly via activation of H1 and H2 receptors. In conclusion, this study demonstrates that histamine can induce phasic contractions of rat distal cauda epididymis via H2 receptors and autonomic neurotransmitters. Histamine may also exert modulatory actions on contractions of rat distal cauda epididymis duct induced by adrenergic receptor agonists. Further studies are necessary to unveil the localization of histamine receptors within the epididymal duct and the consequences of manipulation of the histaminergic system on epididymal function and male fertility.