Comparison of the Risk of Hospitalization and Severe Disease Among Co-circulating Severe Acute Respiratory Syndrome Coronavirus 2 Variants.

BACKGROUND: We compare the risk of coronavirus disease 2019 (COVID-19) outcomes among co-circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants between January 2021 and May 2022 in Navarra, Spain. METHODS: We compared the frequency of hospitalization and severe disease (intensive care unit admission or death) due to COVID-19 among the co-circulating variants. Variants analyzed were nonvariants of concern (non-VOCs), Alpha, Delta, Omicron BA.1, and Omicron BA.2. Logistic regression models were used to estimate adjusted odds ratio (aOR). RESULTS: The Alpha variant had a higher risk of hospitalization (aOR, 1.86 [95 confidence interval {CI}, 1.282.71]) and severe disease (aOR, 2.40 [95 CI, 1.314.40]) than non-VOCs. The Delta variant did not show a significantly different risk of hospitalization (aOR, 0.73 [95 CI, .401.30]) and severe disease (aOR, 3.04 [95 CI, .5716.22]) compared to the Alpha variant. The Omicron BA.1 significantly reduced both risks relative to the Delta variant (aORs, 0.28 [95 CI, .16.47] and 0.23 [95 CI, .12.46], respectively). The Omicron BA.2 reduced the risk of hospitalization compared to BA.1 (aOR, 0.52 [95 CI, .29.95]). CONCLUSIONS: The Alpha and Delta variants showed an increased risk of hospitalization and severe disease, which decreased considerably with the Omicron BA.1 and BA.2. Surveillance of variants can lead to important differences in severity.

Animal models of kidney iron overload and ferroptosis: a review of the literature.

In recent years, it has been identified that excess iron contributes to the development of various pathologies and their complications. Kidney diseases do not escape the toxic effects of iron, and ferroptosis is identified as a pathophysiological mechanism that could be a therapeutic target to avoid damage or progression of kidney disease. Ferroptosis is cell death associated with iron-dependent oxidative stress. To study the effects of iron overload (IOL) in the kidney, numerous animal models have been developed. The methodological differences between these models should reflect the IOL-generating mechanisms associated with human IOL diseases. A careful choice of animal model should be considered for translational purposes.

Efficacy and Security of Tetrodotoxin in the Treatment of Cancer-Related Pain: Systematic Review and Meta-Analysis.

The pharmacological treatment of cancer-related pain is unsatisfactory. Tetrodotoxin (TTX) has shown analgesia in preclinical models and clinical trials, but its clinical efficacy and safety have not been quantified. For this reason, our aim was to perform a systematic review and meta-analysis of the clinical evidence that was available. A systematic literature search was conducted in four electronic databases (Medline, Web of Science, Scopus, and ClinicalTrials.gov) up to 1 March 2023 in order to identify published clinical studies evaluating the efficacy and security of TTX in patients with cancer-related pain, including chemotherapy-induced neuropathic pain. Five articles were selected, three of which were randomized controlled trials (RCTs). The number of responders to the primary outcome (≥30% improvement in the mean pain intensity) and those suffering adverse events in the intervention and placebo groups were used to calculate effect sizes using the log odds ratio. The meta-analysis showed that TTX significantly increased the number of responders (mean = 0.68; 95% CI: 0.19-1.16, p = 0.0065) and the number of patients suffering non-severe adverse events (mean = 1.13; 95% CI: 0.31-1.95, p = 0.0068). However, TTX did not increase the risk of suffering serious adverse events (mean = 0.75; 95% CI: -0.43-1.93, p = 0.2154). In conclusion, TTX showed robust analgesic efficacy but also increased the risk of suffering non-severe adverse events. These results should be confirmed in further clinical trials with higher numbers of patients.

Investigational Drugs for the Treatment of Postherpetic Neuralgia: Systematic Review of Randomized Controlled Trials.

The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical development are addressed in this review. A systematic literature search was conducted in three electronic databases (Medline, Web of Science, Scopus) and in the ClinicalTrials.gov register from 1 January 2016 to 1 June 2023 to identify Phase II, III and IV clinical trials evaluating drugs for the treatment of PHN. A total of 18 clinical trials were selected evaluating 15 molecules with pharmacological actions on nine different molecular targets: Angiotensin Type 2 Receptor (AT2R) antagonism (olodanrigan), Voltage-Gated Calcium Channel (VGCC) α2δ subunit inhibition (crisugabalin, mirogabalin and pregabalin), Voltage-Gated Sodium Channel (VGSC) blockade (funapide and lidocaine), Cyclooxygenase-1 (COX-1) inhibition (TRK-700), Adaptor-Associated Kinase 1 (AAK1) inhibition (LX9211), Lanthionine Synthetase C-Like Protein (LANCL) activation (LAT8881), N-Methyl-D-Aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone and hydromorphone) and Nerve Growth Factor (NGF) inhibition (fulranumab). In brief, there are several drugs in advanced clinical development for treating PHN with some of them reporting promising results. AT2R antagonism, AAK1 inhibition, LANCL activation and NGF inhibition are considered first-in-class analgesics. Hopefully, these trials will result in a better clinical management of PHN.

Decreased survival in children inpatients with COVID-19 and antibiotic prescription.

BACKGROUND: The empirical prescription of antibiotics to inpatients with Coronavirus Disease 2019 (COVID-19) is frequent despite uncommon bacterial coinfections. Current knowledge of the effect of antibiotics on the survival of hospitalized children with COVID-19 is limited. OBJECTIVE: To characterize the survival experience of children with laboratory-positive COVID-19 in whom antibiotics were prescribed at hospital admission. METHODS: A retrospective cohort study was conducted in Mexico, with children hospitalized due to COVID-19 from March 2020 to December 2021. Data from 1601 patients were analyzed using the Kaplan-Meier method and the log-rank test. We computed hazard ratios (HR) and 95% confidence intervals (CI) to evaluate the effect of the analyzed exposures on disease outcomes. RESULTS: Antibiotics were prescribed to 13.2% ([Formula: see text] = 211) of enrolled children and a higher mortality rate [14.9 (95% CI 10.1-19.8) vs. 8.3 (95% CI 6.8-9.8)] per 1000 person-days, [Formula: see text] < 0.001) was found among them. At any given cut-off, survival functions were lower in antibiotic-positive inpatients ([Formula: see text] < 0.001). In the multiple model, antibiotic prescription was associated with a 50% increase in the risk of fatal outcome (HR = 1.50, 95% CI 1.01-2.22). A longer interval between illness onset and healthcare-seeking and pneumonia at hospital admission was associated with a poorer prognosis. CONCLUSIONS: Our results suggest that antibiotic prescription in children hospitalized due to COVID-19 is associated with decreased survival. If later replicated, these findings highlight the need for rational antibiotics in these patients.

Effectiveness of influenza vaccination in preventing influenza in primary care, Navarre, Spain, 2021/22.

Compared with individuals unvaccinated in the current and three previous influenza seasons, in 2021/22, influenza vaccine effectiveness at primary care level was 37% (95% CI: 16 to 52) for current season vaccination, regardless of previous doses, and 35% (95% CI: -3 to 45) for only previous seasons vaccination. Against influenza A(H3N2), estimates were 39% (95% CI: 16 to 55) and 24% (95% CI: -8 to 47) suggesting moderate effectiveness of current season vaccination and possible remaining effect of prior vaccinations.

Multicenter clinical evaluation of a novel transcription-mediated amplification assay for SARS-CoV-2 molecular testing.

INTRODUCTION: The onset and spread of COVID-19 pandemic has forced clinical laboratories to rapidly expand testing capacity for SARS-CoV-2. This study evaluates the clinical performance of the TMA Procleix SARS-CoV-2 assay in comparison to the RT-PCR assay AllplexTM SARS-CoV-2 for the qualitative detection of SARS-CoV-2 RNA. METHODS: Between November 2020 and February 2021, 610 upper-respiratory specimens received for routine SARS-CoV-2 molecular testing were prospectively collected and selected at the Hospital Universitari Vall d'Hebron and the Hospital Universitari Bellvitge in Barcelona, Spain. All samples were processed in parallel with the TMA and the RT-PCR assays, and results were compared. Discrepancies were retested by an additional RT-PCR method and the clinical history of these patients was reviewed. RESULTS: Overall, the level of concordance between both assays was 92.0% (κ, 0.772). Most discordant results (36/38, 94.7%) corresponded to samples testing positive with the TMA assay and negative with the RT-PCR method. Of these discrepant cases, most (28/36, 77.8%) were finally classified as confirmed or probable SARS-CoV-2 cases according to the discrepant analysis. CONCLUSION: In conclusion, the TMA Procleix SARS-CoV-2 assay performed well for the qualitative detection of SARS-CoV-2 RNA in a multisite clinical setting. This novel TMA assay demonstrated a greater sensitivity in comparison to RT-PCR methods for the molecular detection of SARS-CoV-2. This higher sensitivity but also the qualitative feature of this detection of SARS-CoV-2 should be considered when making testing algorithm decisions.

Capsaicin Decreases Kidney Iron Deposits and Increases Hepcidin Levels in Diabetic Rats with Iron Overload: A Preliminary Study.

Iron overload (IOL) increases the risk of diabetes mellitus (DM). Capsaicin (CAP), an agonist of transient receptor potential vanilloid-1 (TRPV1), reduces the effects of IOL. We evaluated the effects of chronic CAP administration on hepcidin expression, kidney iron deposits, and urinary biomarkers in a male Wistar rat model with IOL and DM (DM-IOL). IOL was induced with oral administration of iron for 12 weeks and DM was induced with streptozotocin. Four groups were studied: Healthy, DM, DM-IOL, and DM-IOL + CAP (1 mg·kg-1·day-1 for 12 weeks). Iron deposits were visualized with Perls tissue staining and a colorimetric assay. Serum hepcidin levels were measured with an enzyme-linked immunosorbent assay. Kidney biomarkers were assayed in 24 h urine samples. In the DM-IOL + CAP group, the total area of iron deposits and the total iron content in kidneys were smaller than those observed in both untreated DM groups. CAP administration significantly increased hepcidin levels in the DM-IOL group. Urinary levels of albumin, cystatin C, and beta-2-microglobulin were similar in all three experimental groups. In conclusion, we showed that in a DM-IOL animal model, CAP reduced renal iron deposits and increased the level of circulating hepcidin.

COVID-19 Pneumonia in Fully Vaccinated Adults during the Dominance of the Omicron Sublineages BA.1.1 and BA.2 in Mexico.

Background and Objectives: A nationwide retrospective cohort study was conducted to evaluate the factors associated with the risk of laboratory-confirmed coronavirus disease 2019 (COVID-19)-related pneumonia in fully vaccinated adults during the dominance of the Omicron sublineages in Mexico. Materials and Methods: Fully COVID-19-vaccinated adults with laboratory-positive illness and symptom onset from April to mid-June 2022 were eligible. We computed the eta-squared (η2) to evaluate the effect size of the study sample. The characteristics predicting pneumonia were evaluated through risk ratios (RRs), and the 95% confidence intervals (CIs) were computed through generalized linear models. Results: The data from 35,561 participants were evaluated, and the overall risk of pneumonia was 0.5%. In multiple analyses, patients aged ≥ 60 years old were at increased risk of developing pneumonia (vs. 20−39 years old: RR = 1.031, 95% CI = 1.027−1.034). Chronic pulmonary obstructive disease, type 2 diabetes mellitus, arterial hypertension, chronic kidney disease (any stage), and immunosuppression (any cause) were also associated with a higher pneumonia risk. The η2 of all the variables included in the multiple models was <0.06. Conclusions: Our study suggests that, even when fully COVID-19-vaccinated, older adults and those with chronic conditions were at increased risk of pneumonia during the dominance of the Omicron sublineages BA.1.1 and BA.2.

Evaluation of the Fully Automated Chemiluminescence Analyzer Liaison XL for the Performance of the QuantiFERON-TB Gold Plus Assay in an Area with a Low Incidence of Tuberculosis.

Diagnosis of latent tuberculosis infection (LTBI) is considered key in the control of tuberculosis. Interferon gamma (IFN-γ) release assays, such as the QuantiFERON-TB Gold Plus test (QFT-Plus), are now widely implemented for the in vitro diagnosis of LTBI. To date, the detection and quantification of IFN-γ has been mostly performed with semiautomated enzyme-linked immunosorbent assays (ELISAs), but several limitations currently exist. The study aims to evaluate the chemiluminescence immunoassay (CLIA) analyzer Liaison XL compared to ELISA for the performance of the QFT-Plus test. Between February and April 2020, 333 heparin blood samples from 323 adult patients were collected at a tertiary teaching hospital in Barcelona, Spain. Overall, the CLIA analyzer Liaison XL performed well for the detection of IFN-γ compared to the ELISA method, demonstrating substantial agreement (κ, 0.872) and great correlation between assays (r, >0.950). CLIA produced significantly higher values of IFN-γ IU per milliliter than the ELISA (P = 0.004 for the TB1 tube and P = 0.010 for the TB2 tube). Many discrepant cases (8/15, 53.3%) corresponded to indeterminate results with ELISA (NIL-corrected mitogen value of <0.5 IU/ml), which, when analyzed with the CLIA analyzer Liaison XL, reverted to interpretable results. In conclusion, this analysis suggests that CLIA presents a greater sensitivity for the identification of LTBI, especially among immunocompromised patients. Furthermore, the analytical variability reported between both ELISA and CLIA methods, especially around the standardized 0.35-IU/ml positivity threshold, suggests the need to refine the interpretative algorithm.

Emergence of SARS-CoV-2 Variant B.1.575.2, Containing the E484K Mutation in the Spike Protein, in Pamplona, Spain, May to June 2021.

With the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the acquisition of novel mutations in existing lineages, the need to implement methods capable of monitoring viral dynamics arises. We report the emergence and spread of a new SARS-CoV-2 variant within the B.1.575 lineage, containing the E484K mutation in the spike protein (named B.1.575.2), in a region in northern Spain in May and June 2021. SARS-CoV-2-positive samples with cycle threshold values of ≤30 were selected to screen for presumptive variants using the TaqPath coronavirus disease 2019 (COVID-19) reverse transcription (RT)-PCR kit and the TaqMan SARS-CoV-2 mutation panel. Confirmation of variants was performed by whole-genome sequencing. Of the 200 samples belonging to the B.1.575 lineage, 194 (97%) corresponded to the B.1.575.2 sublineage, which was related to the presence of the E484K mutation. Of 197 cases registered in the Global Initiative on Sharing Avian Influenza Data (GISAID) EpiCoV database as lineage B.1.575.2, 194 (99.5%) were identified in Pamplona, Spain. This report emphasizes the importance of complementing surveillance of SARS-CoV-2 with sequencing for the rapid control of emerging viral variants.

Symptomatic SARS-COV-2 reinfection: healthcare workers and immunosuppressed individuals at high risk.

BACKGROUND: Knowledge regarding factors predicting the SARS-COV-2 reinfection risk is scarce and it has major implications in public health policies. We aimed to identify factors associated with the risk of symptomatic SARS-COV-2 reinfection. METHODS: We conducted a nationwide retrospective cohort study and 99,993 confirmed cases of COVID-19 were analyzed. RESULTS: The overall risk of reinfection (28 or more elapsed days between both episodes onset) was 0.21% (incidence density, 2.5 reinfections per 100,000 person-days) and older subjects and those with the mild primary disease were at reduced risk of the event. Healthcare workers and immunosuppressed or renal patients had at greater risk of SARS-COV-2 reinfection. CONCLUSIONS: If replicated in other populations, these results may be useful to prioritize efforts focusing on the reduction of SARS-COV-2 spread and the related burden.

Product-specific COVID-19 vaccine effectiveness against secondary infection in close contacts, Navarre, Spain, April to August 2021.

COVID-19 vaccine effectiveness by product (two doses Comirnaty, Spikevax or Vaxzevria and one of Janssen), against infection ranged from 50% (95% CI: 42 to 57) for Janssen to 86% (70 to 93) for Vaxzevria-Comirnaty combination; among ≥ 60 year-olds, from 17% (-26 to 45) for Janssen to 68% (48 to 80) for Spikevax; and against hospitalisation from 74% (43 to 88) for Janssen to > 90% for other products. Two doses of vaccine were highly effective against hospitalisation, but suboptimal for infection control.

Are electrophysiological and oligodendrocyte alterations an element in the development of multiple sclerosis at the same time as or before the immune response?

Efficient communication between the glial cells and neurons is a bi-directional process that is essential for conserving normal functioning in the central nervous system (CNS). Neurons dynamically regulate other brain cells in the healthy brain, yet little is known about the first pathways involving oligodendrocytes and neurons. Oligodendrocytes are the myelin-forming cells in the CNS that are needed for the propagation of action potentials along axons and additionally serve to support neurons by neurotrophic factors (NFTs). In demyelinating diseases, like multiple sclerosis (MS), oligodendrocytes are thought to be the victims. Axonal damage begins early and remains silent for years, and neurological disability develops when a threshold of axonal loss is reached, and the compensatory mechanisms are depleted. Three hypotheses have been proposed to explain axonal damage: 1) the damage is caused by an inflammatory process; 2) there is an excessive accumulation of intra-axonal calcium levels; and, 3) demyelinated axons evolve to a degenerative process resulting from the lack of trophic support provided by myelin or myelin-forming cells. Although MS was traditionally considered to be a white matter disease, the demyelination process also occurs in the cerebral cortex. Recent data supports the notion that initial response is triggered by CNS injury. Thus, the understanding of the role of neuron-glial neurophysiology would help provide us with further explanations. We should take in account the suggestion that MS is in part an autoimmune disease that involves genetic and environmental factors, and the pathological response leads to demyelination, axonal loss and inflammatory infiltrates.

Effectiveness of BNT162b2 COVID-19 Vaccine in Preventing Severe Symptomatic Infection among Healthcare Workers.

Background and Objectives: This study aims to evaluate the effectiveness of the BNT162b2 COVID-19 (coronavirus disease 2019) in preventing severe symptomatic laboratory-confirmed infection among healthcare workers in a real-world scenario. Materials and Methods: A cross-sectional analysis of a prospective cohort study was conducted. Subjects with onset illness from January to February 2021 were eligible and classified according to the number of vaccine doses received (single-shot, n = 8; two-shot, n = 12; unvaccinated, n = 290). Results: The vaccine effectiveness against severe illness was 100% in the single and two-shot group. The presented results suggest that vaccination reduces the frequency of severe symptomatic COVID-19 in working-age adults. Conclusions: Efforts focusing on maximizing the number of immunized subjects in the study population may reduce associated economic and social burdens.

Performance of Antigen-Based Testing as Frontline Diagnosis of Symptomatic COVID-19.

Background and Objectives: To evaluate the performance of antigen-based detection tests as the frontline diagnosis of coronavirus disease 2019 (COVID-19). Materials and Methods: We conducted a nationwide retrospective cohort study in Mexico. A cross-sectional analysis of a cohort study was conducted in Mexico and data from 15,408 suspected (all of them symptomatic) cases of COVID-19 were analyzed. The results of antigen-based tests were compared with those obtained by molecular (polymerase chain reaction-based) assays. Results: The antigen-based tests showed sensitivity below 50% and high specificity in all the analyzed age groups. The highest Youden index (J) was observed among adults aged 25-44 years old (45.5, 95% CI 43.7-47.3). Conclusions: We documented the poor performance of serologic techniques as frontline diagnosis of symptomatic COVID-19 and inaccurate results may impact negatively on pandemic progression.

Single-Locus-Sequence-Based Typing of the mgpB Gene Reveals Transmission Dynamics in Mycoplasma genitalium.

Sexually transmitted infections (STIs) by Mycoplasma genitalium are a major problem worldwide, especially given their marked and rapid propensity for developing antimicrobial resistance. Since very few treatment options exist, clinicians face an important challenge in the management of the infection. In this scenario, little is known regarding the transmission dynamics of M. genitalium and the epidemiology of antimicrobial resistance. This mgpB-based molecular typing study, conducted among 54 asymptomatically infected individuals prospectively recruited from an STI screening service, reveals two distinct epidemiological clusters that significantly correlate with sexual conduct in heterosexuals and men who have sex with men (MSM), respectively. This well-defined structuration suggests the presence of two independent sexual networks with little connectivity between them. On the other hand, the study demonstrates the multiclonal feature of the emergence of antibiotic resistance in M. genitalium to both macrolides and fluoroquinolones. The high prevalence of macrolide resistance in M. genitalium among MSM, influenced by dense network connectivity and strong antibiotic selective pressure, may correspond to allodemics affecting other STIs such as gonorrhea, syphilis and enteric pathogens. Collaterally, the structural and functional impact of mutations in the mgpB gene, encoding the major adhesin P140 (MgpB), may require further investigation.

Prevalence of Mycoplasma genitalium and macrolide resistance among asymptomatic people visiting a point of care service for rapid STI screening: a cross-sectional study.

OBJECTIVES: Although rapid screening and treatment programmes have been recently implemented to tackle STIs, testing Mycoplasma genitalium (MG) among asymptomatic populations is not currently recommended due to the lack of scientific evidence and the emergence of antibiotic resistance. The main objective of this study was to estimate the prevalence of MG and macrolide resistance among asymptomatic people visiting a point of care service for rapid STI screening and to identify risk factors associated with the acquisition of this infection. METHODS: Between October 2017 and January 2018, a total of 890 asymptomatic individuals attending to the STI screening service Drassanes Exprés in Barcelona, Spain, were tested for MG and macrolide resistance using the molecular ResistancePlus MG assay (SpeeDx, Australia). Asymptomatically infected individuals were invited to attend the STI Unit for resistance-guided antimicrobial therapy. RESULTS: Overall, the prevalence of MG was 7.4% (66/890; 95% CI 5.8% to 9.3%), being higher among men who have sex with men (MSM) (46/489) compared with heterosexual men and women (20/401; p=0.012). Macrolide resistance was found in 32/46 (69.6%; 95% CI 54.2% to 82.3%) MSM, while only 2/20 (10.0%; 95% CI 1.2% to 31.7%) infections among heterosexuals presented macrolide resistance-mediated mutations (p<0.001). MSM behaviour, receptive anal intercourse, HIV positive status, syphilis history and high-risk sexual activity (more than five sexual partners in the last 3 months) were significantly associated with MG infection. Furthermore, the resistance-guided therapy approach was implemented in 36/66 (54.6%) individuals. CONCLUSIONS: The research provides further data regarding the prevalence of MG and macrolide resistance among asymptomatic individuals. It also identifies higher risk subpopulations which might be targets for MG screening. Nevertheless, there is insufficient data to justify MG testing among asymptomatic individuals and current STI guidelines should be followed until evidence shows the cost and effectiveness of screening.

Male gender and kidney illness are associated with an increased risk of severe laboratory-confirmed coronavirus disease.

BACKGROUND: To identify factors predicting severe coronavirus disease 2019 (COVID-19) in adolescent and adult patients with laboratory-positive (quantitative reverse-transcription polymerase chain reaction) infection. METHOD: A retrospective cohort study took place, and data from 740 subjects, from all 32 states of Mexico, were analyzed. The association between the studied factors and severe (dyspnea requiring hospital admission) COVID-19 was evaluated through risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Severe illness was documented in 28% of participants. In multiple analysis, male gender (RR = 1.13, 95% CI 1.06-1.20), advanced age ([reference: 15-29 years old] 30-44, RR = 1.02, 95% CI 0.94-1.11; 45-59, RR = 1.26, 95% CI 1.15-1.38; 60 years or older, RR = 1.44, 95% CI 1.29-1.60), chronic kidney disease (RR = 1.31, 95% CI 1.04-1.64) and thoracic pain (RR = 1.16, 95% CI 1.10-1.24) were associated with an increased risk of severe disease. CONCLUSIONS: To the best of our knowledge, this is the first study evaluating predictors of COVID-19 severity in a large subset of the Latin-American population. Male gender and kidney illness were independently associated with the risk of severe COVID-19. These results may be useful for health care protocols for the early detection and management of patients that may benefit from opportune and specialized supportive medical treatment.

Type 2 Diabetes Alters Vascular Cannabinoid Receptor 1 Expression, Phosphorylation Status, and Vasorelaxation in Rat Aorta.

Previous studies have suggested a role of the endocannabinoid system in metabolic diseases, such as diabetes. We investigated the effect of diabetes on cannabinoid receptor type 1 (CB1) expression and cannabinoid-induced vasorelaxation in rat aorta rings. Aortas from healthy rats and from rats with experimentally induced diabetes were used to compare the vasorelaxant effect of the cannabinoid agonist arachidonylcyclopropylamide (ACPA) and CB1 expression and localization. After 4-8 weeks of diabetes induction, CB1 receptor expression and CB1 phosphorylation were higher in aortic rings, in association with greater vasorelaxation induced by the CB1 agonist ACPA compared to healthy rats. The vasorelaxant effect observed in healthy rats is similar throughout the study. Further studies are needed to elucidate the implications of CB1 receptor overexpression in diabetes and its influence on the progression of the cardiovascular complications of this metabolic disease.