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Background: Respiratory distress syndrome is a complex inflammatory condition defined by the presence of acute hypoxemia and cellular infiltration with diffuse alveolar injury following a tissue injury, such as acute lung injury. The inflammatory process involved in this pathology is a defense mechanism of the body against infectious agents and/or tissue injuries. However, when the condition is not reversed, it becomes a significant cause of tissue damage, sometimes leading to loss of function of the affected organ. Therefore, it is essential to understand the mechanisms underlying inflammation, as well as the development of new therapeutic agents that reduce inflammatory damage in these cases. Aryl-cyclohexanone derivatives have previously shown significant anti-inflammatory activity linked to an immunomodulatory capacity in vitro and may be good candidates for therapies in which inflammation plays a central role., Methods: Was evaluated the anti-inflammatory capacity of a synthesized molecule aryl-cyclohexanone in the murine model of lipopolysaccharide (LPS)-induced acute lung injury. The assessment of acute oral toxicity follows the Organization for Economic Co-operation and Development (OECD) guideline 423., Results: The results demonstrated that the studied molecule protects against LPS-induced inflammation. We observed a decrease in the migration of total and differential leukocytes to the bronchoalveolar lavage fluid (BALF), in addition to a reduction in exudation, myeloperoxidase (MPO) activity, nitric oxide metabolites, and the secretion of pro-inflammatory cytokines (alpha tumor necrosis factors [TNF-α], interleukin-6 [IL-6], interferon-gamma [IFN-γ], and monocyte chemoattractant protein-1 [MCP-1]). Finally, aryl cyclohexanone did not show signs of acute oral toxicity (OECD 423)., Conclusions: The results prove our hypothesis that aryl-cyclohexanone is a promising molecule for developing a new, safe anti-inflammatory drug., (© 2024 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.)

Introduction: Inflammation is a physiological event that protects the organism against different factors that lead to loss of tissue homeostasis. Dihydropyridine (DHP) derivatives are heterocyclic compounds known for their different biological activities, including anti-inflammatory activities., Objective: To evaluate the anti-inflammatory activity of 1,4-dihydropyridine (1,4-DHP) derivatives using anti-inflammatory models in vitro, in RAW264.7 cells induced by lipopolysaccharide (LPS) and in vivo using the acute lung injury (ALI) model in mice., Results: Fifteen compounds derived from 1,4-DHP were tested in RAW264.7 cells for their cytotoxic effect and cell viability. Thereafter, only the six compounds that showed the highest cell viability were tested for the production or inhibition of the pro-inflammatory cytokine interleukin 6 (IL-6). The best compound (compound 4) was tested for its anti-inflammatory effects in vitro and in vivo, showing inhibition of nitric oxide (NO), pro-inflammatory cytokines, increased phagocytic activity, and an increase in IL-10 in vitro. In in vivo tests, compound 4 also reduces the levels of NO, myeloperoxidase (MPO) activity, leukocyte migration, and exudation, as well as reducing the levels of tumor necrosis factor-alpha (TNF-α) and IL-6 and preventing the loss in the lung architecture., Conclusion: This compound showed important anti-inflammatory activity, with a significant ability to reduce the production of pro-inflammatory mediators and increase the phagocytic activity of macrophages and anti-inflammatory mediator secretion (IL-10). These findings led us to hypothesize that this compound can repolarize the macrophage response to an anti-inflammatory profile (M2). Moreover, it was also able to maintain its anti-inflammatory activity in vivo experiments., (© 2023 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.)

Guanosine is a purinergic nucleoside that has been shown to have neuroprotective effects, mainly through its ability to modulate the glutamatergic system. An increase in pro-inflammatory cytokine levels triggers the activation of the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), leading to glutamatergic excitotoxicity, which has important roles in the pathophysiology of depression. The aim of this study was to investigate the possible antidepressant-like effects and underlying mechanisms of action of guanosine against lipopolysaccharide (LPS)-induced depression in a mouse model. Mice were orally pre-treated with saline (0.9% NaCl), guanosine (8 or 16 mg/kg), or fluoxetine (30 mg/kg) for 7 days before LPS (0.5 mg/kg, intraperitoneal) injection. One day after LPS injection, mice were subjected to the forced swim test (FST), tail suspension test (TST), and open field test (OFT). After the behavioral tests, mice were euthanized and the levels of tumor necrosis factor-α (TNF-α), IDO-1, glutathione, and malondialdehyde in the hippocampus were measured. Pretreatment with guanosine was able to prevent LPS- induced depressive-like behaviors in the TST and FST. In the OFT, no locomotor changes were observed with any treatment. Both guanosine (8 and 16 mg/kg/day) and fluoxetine treatment prevented the LPS-induced increase in TNF-α and IDO expression and lipid peroxidation as well as decrease of reduced glutathione levels in the hippocampus. Taken together, our findings suggest that guanosine may have neuroprotective effects against LPS-induced depressive-like behavior through preventing oxidative stress and the expression of IDO-1 and TNF-α in the hippocampus., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ziliani da Silva Buss reports financial support was provided by National Council for Scientific and Technological Development., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Clinical studies indicate that alcohol-dependent patients may develop depressive symptoms during abstinence, which may increase the likelihood of relapse. It is known that both in alcohol exposure and depression, there is an increase in the levels of pro-inflammatory cytokines in the brain. However, the putative contribution of increased levels of pro-inflammatory cytokines in the development of depressive-like behavior during ethanol withdrawal has not been evaluated. In the present study, we aimed to investigate if ethanol withdrawal-induced depressive-like behavior is related to increased levels of pro-inflammatory cytokines in the brain. Male mice were treated with vehicle (saline 0.9%, v.o.) or ethanol (2 g/kg, v.o.) for 14 days. After 5 days of cessation of the ethanol treatment, mice were subjected to the forced swim test (FST), tail suspension test (TST), and open field test (OFT) and then sacrificed. Their brains were analyzed for the levels of pro-inflammatory cytokines. Ethanol withdrawal mice showed increased immobility time in the FST and TST than by the control group, indicating increased depressive-like behavior. No alterations in OFT were observed. Ethanol withdrawal increased the levels of tumor necrosis factor-alpha (TNF-α) in the hippocampus and striatum, interleukin-1 beta (IL-1β) in the hippocampus, and IL-6 in the prefrontal cortex and hippocampus. Treatment of mice with nimesulide (5 or 10 mg/kg/day), a cyclooxygenase-2 inhibitor, during ethanol withdrawal prevented the increase in immobility time in the TST. Similar results were observed in the FST upon nimesulide treatment, although with a higher dose. Nimesulide treatment (10 mg/kg) prevented the ethanol withdrawal-induced alterations in the levels of TNF-α, IL-1β, and IL-6 in the hippocampus, prefrontal cortex, and striatum. Treatment of mice with an atypical antidepressant drug, vilazodone (0.3 or 1 mg/kg) prevented the increase in depressive-like behavior induced by ethanol withdrawal in the TST. In the FST, the increase in immobility time was prevented only by 1 mg/kg vilazodone treatment. Vilazodone prevented the increase in the levels of TNF-α, IL-1β, and IL-6 in the hippocampus, IL-6 in the prefrontal cortex, and TNF-α in the striatum. In conclusion, these data indicate that increased levels of pro-inflammatory cytokines may play a role in the development of depressive-like behavior during ethanol withdrawal in mice., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The present study evaluated the antidepressant-like effects of vilazodone using the tail suspension test in mice. We also investigated the contribution of kynurenine pathway and N-methyl-d-aspartate receptors to this effect. For this purpose, we pretreated animals with sub-effective doses of L-kynurenine, 3-hydroxykynurenine, or quinolinic acid. We then assessed the immobility time, an indicative measure of depressive-like behavior, in the tail suspension test. We also evaluated the possible effects of sub-effective doses of vilazodone combined with sub-effective doses of ketamine (N-methyl-d-aspartate receptor antagonist) in a separate group. Vilazodone (3mg/kg, intraperitoneal) significantly reduced immobility time in the tail suspension test. L-kynurenine (1.7 mg/kg, intraperitoneal), 3-hydroxykynurenine (10 mg/kg, intraperitoneal), and quinolinic acid (3 nmol/site, intracerebroventricular) significantly increased the immobility time in the tail suspension test. The antidepressant-like effects of vilazodone (3mg/kg, intraperitoneal) were inhibited by pre-treatment with non-effective doses of L-kynurenine (0.83 mg/kg, intraperitoneal), 3-hydroxykynurenine (3.33 mg/kg, intraperitoneal), or quinolinic acid (1 nmol/site, intracerebroventricular). Pretreatment of mice with sub-effective doses of ketamine (1 mg/kg, intraperitoneal) optimized the action of a sub-effective dose of vilazodone (0.3mg/kg, intraperitoneal) and reduced the immobility time in the tail suspension test. None of the drugs used in this study induced any changes in locomotor activity in the open field test. The results showed that vilazodone induced an antidepressant-like effect in the tail suspension test, which may be mediated through an interaction with the kynurenine pathway and N-methyl-d-aspartate receptors., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Rates of HIV, syphilis and gonorrhoea have increased over the past 20 years in men who have sex with men (MSM). Contact tracing strategies have increased the number of MSM attending clinics as sexual contacts. Understanding the outcomes of contact tracing could inform future public health policies to reduce the burden of STIs in MSM., Method: We aimed to describe the contribution of MSM attending as notified sexual contacts of patients with HIV, syphilis and gonorrhoea to the overall diagnoses of HIV, syphilis and gonorrhoea in MSM in a cross-sectional study. We collected data on all MSM diagnosed with HIV, syphilis and gonorrhoea in 2019 and evaluated which of these MSM were tested due to attending as a sexual contact., Results: Sexual contacts of HIV, syphilis and gonorrhoea contributed to 20% (95% CI=17.3% to 23.7%) of all diagnoses of HIV (3 of 30, 10%), syphilis (28 of 183, 15%) or gonorrhoea (98 of 420, 23%) in the study period. Asymptomatic sexual contacts contributed to 12% (95% CI=9.6% to 14.9%) of all diagnoses of HIV (3 of 30, 10%), syphilis (16 of 183, 9%) and gonorrhoea (57 of 420, 14%). The proportion of MSM diagnosed with gonorrhoea attending as sexual contacts of gonorrhoea (21%) was significantly greater than MSM diagnosed with HIV, attending as sexual contacts of HIV (3%) or MSM diagnosed with syphilis, attending as a sexual contact of syphilis (4%) (p<0.001). Furthermore, the proportion of MSM diagnosed with syphilis, attending as a sexual contact of another STI (11%) was significantly greater than MSM diagnosed with HIV, attending as a contact of another STI (7%) or MSM diagnosed with gonorrhoea, attending as a sexual contact of another STI (2%) (p<0.001)., Conclusion: Contact tracing contributes significantly to the overall diagnoses of HIV, syphilis and gonorrhoea including asymptomatic sexual contacts in our population. Further efforts to increase the yield from contact tracing may continue to reduce the burden of HIV, syphilis and gonorrhoea within sexual networks of MSM., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: There has been a significant increase in syphilis in men who have sex with men (MSM) in the UK over the past 20 years. Partner notification strategies have increased the number of MSM attending STI clinics as sexual contacts of syphilis. Current guidelines suggest testing and consideration of presumptive antimicrobial treatment. Syphilis treatment with benzathine penicillin requires clinic resources, is painful and is associated with complications. It is important we consider strategies to rationalise presumptive antimicrobial use and promote antimicrobial stewardship., Methods: We aimed to determine if there are any factors associated with having syphilis among MSM attending as sexual contacts of syphilis in a cross-sectional study. We examined the clinical records of MSM attending as sexual contacts of syphilis from January to December 2019., Results: Of the 6613 MSM who attended for STI testing, 142 of 6613 (2.1%) presented as sexual contacts of syphilis. The median age was 40 years (IQR=31-51), 43 of 142 (30%) were HIV positive, 38 of 142 (27%) had been diagnosed and treated for syphilis in the past, and 11 of 142 (8%) presented with symptoms (possible lesions of primary or secondary syphilis). Thirteen (9%, 95% CI=4.4 to 13.9) tested positive for syphilis on the day of presentation. MSM who were symptomatic (genital ulcer or body rash), HIV positive or had a history of syphilis were significantly more likely to test positive for syphilis (OR=51.88, 95% CI: 3.01 to 893.14, p=0.007)., Conclusions: We have shown that in our clinic-based population of MSM who presented as sexual contacts of syphilis, the factors associated with testing positive for syphilis were: having HIV, having a history of syphilis or presenting with symptoms (possible lesions of primary or secondary syphilis). These factors could be used to rationalise antibiotic treatment among MSM presenting as sexual contacts of syphilis. Further research is needed to validate this finding in other populations of MSM and people affected by syphilis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Pharyngeal gonorrhoea is important in the transmission dynamics of gonorrhoea , and generation of antimicrobial resistance and the performing of culture remains vital. We reviewed the notes of men who have sex with men (MSM) presenting to our clinic with a positive pharyngeal NAAT for gonorrhoea between January and December 2019. There were 383 cases of NAAT-positive pharyngeal gonorrhoea , and 28 (7%, 95% CI = 5.11-10.36) reported sore throat at presentation. Pharyngeal cultures were taken from 270/383 (70%), and 73/270 (27%) were culture positive with available antimicrobial sensitivities. Overall, the presence of pharyngeal symptoms was not associated with pharyngeal chlamydia (OR = 1.6, CI = 0.19-13.32, p = 0.7), HIV status (OR = 1.1, CI = 0.47-2.57, p = 0.8), positive cultures (OR = 1.9, CI = 0.78-4.62, p = 0.2) or age ( p = 0.3). Routine screening of MSM for pharyngeal gonorrhoea is important to maintain surveillance and measures need to be taken to improve pharyngeal culture sampling from MSM.

The characteristics and serological responses of primary syphilis are not completely understood. We aimed to describe the characteristics, the serological responses and presumptive treatment of primary syphilis in HIV-positive and -negative men who have sex with men (MSM). We conducted a retrospective review of microbiological and demographic information from MSM presenting with primary syphilis. There were 111 cases of primary syphilis in MSM, the median age was 46 (IQR = 37-53years) and 40 (36%) were living with HIV. Fifty percent of MSM presented with painful lesions and 14% with extra-genital lesions. Extra-genital lesions were significantly more likely to be painful than non-genital lesions (OR 4.72; 95%CI = 1.25-17.83, p = 0.02). Overall, a reactive serological response demonstrated a sensitivity of 80% (57/71) compared with Treponema pallidum PCR. Serology was more sensitive in MSM with no previous syphilis (OR = 3.38, 95%CI = 1.00-11.43, p < 0.05). MSM presenting with painless lesions were more likely to be treated presumptively (OR = 3.39, 95%CI = 1.38-8.33, p < 0.002). There were no differences in the characteristics, serological responses or management according to HIV status. Fifty percent of MSM with primary syphilis presented with painful lesions; extra-genital lesions are more likely to be painful than genital lesions, serology is positive in 80% and there were no differences between HIV-positive and -negative MSM. Understanding the characteristics of primary syphilis will underpin public health campaigns.

Clinical and pre-clinical evidences indicate an association between inflammation and depression since increased levels of pro-inflammatory cytokines are associated with depression-related symptoms. Atorvastatin is a cholesterol-lowering statin that possesses pleiotropic effects including neuroprotective and antidepressant actions. However, the putative neuroprotective effect of atorvastatin treatment in the acute inflammation mice model of depressive-like behaviour has not been investigated. In the present study, we aimed to investigate the effect of atorvastatin treatment on lipopolysaccharide (LPS) induced depressive-like behaviour in mice. Mice were treated with atorvastatin (1 or 10 mg/kg, v.o.) or fluoxetine (30 mg/kg, positive control, v.o.) for 7 days before LPS (0.5 mg/kg, i.p.) injection. Twenty four hours after LPS infusion, mice were submitted to the forced swim test, tail suspension test or open field test. After the behavioural tests, mice were sacrificed and the levels of tumour necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF), glutathione and malondialdehyde were measured. Atorvastatin (1 or 10 mg/kg/day) or fluoxetine treatment prevented LPS-induced increase in the immobility time in the forced swim and tail suspension tests with no alterations in the locomotor activity evaluated in the open field test. Atorvastatin (1 or 10 mg/kg/day) or fluoxetine treatment also prevented LPS-induced increase in TNF-α and reduction of BDNF levels in the hippocampus and prefrontal cortex. Treatment with atorvastatin (1 or 10 mg/kg/day) or fluoxetine prevented LPS-induced increase in lipid peroxidation and the reduction of glutathione levels in the hippocampus and prefrontal cortex. The present study suggests that atorvastatin treatment exerted neuroprotective effects against LPS-induced depressive-like behaviour which may be related to reduction of TNF-α release, oxidative stress and modulation of BDNF expression., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Accumulating evidence indicates an interaction between inflammation and depression since increased levels of pro-inflammatory cytokines are associated with depression-related symptoms. Melatonin is a hormone synthesized and secreted by the pineal gland with antioxidant, anti-inflammatory and antidepressant-like effects. In this way, it would be interesting to evaluate the putative antidepressant-like effect of melatonin treatment in an acute inflammation mice model of depression. The present study aimed to investigate the effect of melatonin treatment on lipopolysaccharide (LPS) induced depressive-like behavior, neuroinflammation, oxidative stress and alteration on brain-derived neurotrophic fator (BDNF) levels. Mice were treated with melatonin (10 mg/kg, i.p.) 30 min before LPS (0.5 mg/kg, i.p.) injection. Twenty-four hours after LPS infusion, mice were submitted to the behavioral tests and, thereafter, biochemical determinations were performed. Melatonin treatment prevented LPS-induced depressive-like behavior in the forced swim and tail suspension tests with no alterations in locomotor activity evaluated in the open field test. Melatonin attenuated LPS-induced increase in tumor necrosis factor-α (TNF-α) and reduction of BDNF levels in the hippocampus. Treatment with melatonin also prevented LPS-induced increase in lipid peroxidation and the reduction of glutathione levels in the hippocampus. In conclusion, the present study suggests that melatonin treatment exerted neuroprotective effects against LPS-induced depressive-like behavior which may be related to reduction of TNF-α release, oxidative stress and modulation of BDNF expression., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To evaluate the parameters associated with quality of life in patients with Paget's disease of bone., Methods: Patients with Paget's disease of bone were evaluated with SF-36 and WHOQOL-bref questionnaires. Patients with other diseases that could cause significant impairment of their quality of life were excluded. We searched for correlations between the results and: age, time from diagnosis, type of involvement, pain related to Paget's disease of bone, limitation to daily activities, deformities, bone specific alkaline phosphatase, the extent of involvement and treatment., Results: Fifty patients were included. Results of the SF-36 total score and its domains, physical and mental health, were significantly correlated with bone pain and deformities. Marital status was significantly correlated with the SF-36 total score and Mental Health Domain. BAP levels and disease extension were significantly correlated to SF-36 Physical Health Domain. After multivariate analysis, the only parameters that remained significantly associated with the SF-36 total score and to its Mental Health and Physical Health Domains were pain and marital status. The WHOQOL-bref total score was significantly associated with pain, physical impairment and deformities. WHOQOL-bref Domain 1 (physical) score was significantly associated with marital status, pain and deformities, while Domain 2 (psychological) score was associated with marital status, physical impairment and kind of involvement. After multivariate analysis, the presence of pain, deformities, and marital status were significantly associated with results of the WHOQOL-bref total score and its Domain 1. WHOQOL-bref domain 2 results were significantly predicted by pain and marital status., Conclusion: The main disease-related factor associated with SF-36 results in Paget's disease of bone patients was bone pain, while bone pain and deformities were associated with WHOQOL-bref., (Copyright © 2017 Elsevier Editora Ltda. All rights reserved.)

This study was undertaken to evaluate the expression of inflammatory cytokines in patients with Paget's disease of bone (PDB). Serum levels of tumoral necrosis factor-α, interleukin 1β, interleukin-6 and interleukin-17 were measured in 51 patients with PDB and in 24 controls with primary osteoarthritis. Compared to controls, patients with Paget's disease of bone presented higher levels of interleukin 6 and reduced interleukin 17, but levels of tumoral necrosis factor α and interleukin 1 β did not differ significantly. We found no significant differences when patients were compared according to disease activity or current treatment. There were no correlations between cytokine levels and bone-specific alkaline phosphatase or extension of Paget's disease of bone on bone scintigraphs. In conclusion, patients with PDB present significant differences on levels of certain cytokines in comparison to primary osteoarthritis patients, but these alterations did not appear to have a clear correlation with parameters of disease activity or severity., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Latex allergy has emerged as a major cause of allergic reactions in health care workers. However, information is limited regarding the diagnostic methods available., Objective: The aim of this study was to investigate diagnostic performance (sensitivity, specificity, and predictive values) of screening for natural rubber latex sensitization by questionnaire among health care workers, using skin prick test (SPT) as the gold standard for diagnosis., Methods: The study population consisted of 260 randomly selected health care workers from the public health units in the city of Florianopolis, Brazil. The subjects were recruited from 2 groups: those who used latex gloves in their work (140) and those who were not exposed to latex (120). The mean (SD) age of the study population was 38.6 (0.6) years. Logistic regression analysis was used to predict SPT result from the questionnaire on previous symptoms of latex sensitization., Results: Symptoms of (1) dryness, fissuring, swelling, pruritus, or cutaneous rash on the hands, and (2) pruritus of the oral mucosa or local redness after eating certain fruits (avocados, bananas, kiwis, chestnuts, mango, melons, or peaches) were the most sensitive and specific questionnaire items, respectively. The combination of these items with a cutoff point derived from the logistic regression led to 100% sensitivity and specificity for the prediction of SPT results in the population studied, with 95% confidence intervals of 51.7% to 100% for sensitivity and 98.1% to 100% for specificity., Conclusion: A questionnaire applied in a group of health care workers displayed excellent screening performance for latex sensitization.

Background: Natural rubber latex allergy is a "new" illness whose prevalence has reached epidemic proportions in highly exposed populations such as health care professionals., Objective: The aim of the study was to evaluate the frequency of reactions to latex and risk factors due to glove use in health care workers (HCW) in Florianopolis, Santa Catarina, Brazil., Methods: We evaluated latex-related allergy in 260 HCW by means of a questionnaire, skin prick tests (SPT) and serum latex specific IgE antibody levels. The subjects were divided into two groups depending on level of exposure to latex gloves. Comparisons were made between the different variables and a risk score was calculated using logistic regression analysis., Results: Glove-related symptoms were observed in 57% of 140 HCW. Significant differences between HCW and control groups were found for the following symptoms: contact dermatitis (P < .0001), cutaneous rash (P < .0001), asthma or allergic rhinitis (P < .0001), symptoms associated with toy balloons (P < .0001), airborne glove powder causing latex allergen reaction (P < .0001), food allergy (P < .0001), fruit allergy (P < .0001) and multiple surgical interventions (P = .0052). Contact dermatitis and anaphylaxis were the main problems, with a high risk factor for the development of latex allergy. Logistic regression analysis showed a significant positive association between the risk of latex allergy and those subjects who reported more than 4 positive answers on the questionnaire (including SPT) (odds ratio 6.8; 95% confidence interval 0.7-60.3). No latex-related allergy symptoms were reported by the control group. Serological latex specific immunoglobulin (Ig) E antibody levels were negative for both groups., Conclusion: It is essential to recognize which professionals are sensitized to latex in order to provide appropriate treatment and to establish adequate prevention.