RESUMEN

In the context of neglected diseases, tegumentary leishmaniasis (TL) presents an emerging and re-emerging character in the national territory and in the world. The treatment of TL has limitations, such as intravenous administration route, high toxicity, and high treatment costs. Thus, several researchers work on new therapeutic strategies to improve the effectiveness of the treatment of leishmaniasis. In this light, the present study used a topical formulation, containing 8-hydroquinoline (8-HQN), for the treatment of Balb/c mice infected with L. amazonensis. After the treatment, the mean diameter of the lesion was measured, as well as the parasite load in organs and immunological parameters associated with the treatment. The results showed that the animals treated with 8-HQN 5%, when compared to controls, showed a reduction in the mean diameter of the lesion and in the parasite load. The animals treated with the ointment showed a type 1 cellular immune response profile associated with the production of cytokines such as INF-γ and TNF-α. In addition, the treatment did not demonstrate toxicity to mice. Therefore, the topical formulation containing 8-HQN 5% is a promising candidate in the topical treatment and could be considered, in the future, as an alternative for the treatment of TL.

Asunto(s)

RESUMEN

AIM: To identify risk factors for falls in older adults with Type 2 Diabetes Mellitus (T2DM). METHODS: The eligible studies identified factors associated with the risk of falls in older adults with T2DM. We searched PubMed, Cinahl, Web of Science, Scopus, and the Cochrane Library databases. The review has been updated and the last review date was November 30, 2023 (CRD42020193461). RESULTS: Twelve studies met the inclusion criteria, and eight studies were included in the meta-analysis. These studies included a total of 40,778 older adults with T2DM, aged 60 to 101 years. The risk of developing the outcome falls in older adults with T2DM is 63% higher compared to the risk in older adults without T2DM (HR 1.63; 95% CI [1.30 - 2.05]). The overall chance of falling in older adults with T2DM is 59% higher than that of non-diabetic older adults (OR 1.59; 95% CI [1.36 -1.87]), and in older adults with T2DM who take insulin the chance of falling is 162% higher (OR 2.62; 95% CI [1.87 - 3.65]). No results on diabetic polyneuropathy were found in the studies. CONCLUSION: Older adults with T2DM present a higher risk of falls compared to non-diabetics. Among the included older adults with T2DM, the most important factor associated with a higher risk of falls was insulin use. TRIAL REGISTRATION: Registered in the International Prospective Register of Systematic Reviews (CRD42020193461).

Asunto(s)

RESUMEN

Microglia are glial cells centrally related to pathophysiology and neuroimmunological regulation of pain through microglia-neuron crosstalk mechanisms. In contrast, anti-inflammatory mechanisms guided by immunological effectors such as IL-10 trigger the secretion of analgesic substances, culminating in the differential expression of genes encoding endogenous opioid peptides, especially ß-endorphin. Thus, when ß-endorphin binds to the µ-opioid receptor, it generates neuronal hyperpolarization, inhibiting nociceptive stimuli. This review aimed to summarize the recent advances in understanding the mechanism by which IL-10/ß-endorphin can reduce pain. For this, databases were searched for articles from their inception up until November 2022. Two independent reviewers extracted the data and assessed the methodological quality of the included studies, and seventeen studies were considered eligible for this review. Several studies have demonstrated the impact of IL-10/ß-endorphin in reducing pain, where IL-10 can stimulate GLP-1R, GRP40, and α7nAChR receptors, as well as intracellular signaling pathways, such as STAT3, resulting in increased ß-endorphin expression and secretion. In addition, molecules such as gabapentinoids, thalidomide, cynandione A, morroniside, lemairamin, and cinobufagin, as well as non-pharmacological treatments such as electroacupuncture, reduce pain through IL-10 mediated mechanisms, reflecting a microglia-dependent ß-endorphin differential increase. This process represents a cornerstone in pain neuroimmunology knowledge, and the results obtained by different studies about the theme are presented in this review.

RESUMEN

In the present study, an immunoproteomic approach using Leishmania infantum parasites isolated from naturally infected dogs from an endemic region of the disease, was carried out to identify new antigens to be used in the diagnosis of canine visceral leishmaniasis (CVL). Protein extracts, obtained from parasites isolated from asymptomatic (CanLA) and symptomatic (CanLS) dogs, were used to perform the two-dimensional gels. Western Blotting assays were carried out by employing a pool of sera from dogs with visceral leishmaniasis (CanLA or CanLS), healthy dogs from an endemic area, or dogs with similar diseases associated with cross-reactions (babesiosis and ehrlichiosis). With these results, it was possible to exclude the spots that showed a cross-reactivity of the sera from groups of healthy dogs, and those with babesiosis or ehrlichiosis. Taken together, 20 proteins were identified, 15 of which have already been described in the literature and 5 of which are hypothetical. An immunogenomic screen strategy was applied to identify conserved linear B-cell epitopes in the identified hypothetical proteins. Two peptides were synthesized and tested in ELISA experiments as a proof of concept for the validation of our immunoproteomics findings. The results demonstrated that the antigens presented sensitivity and specificity values ranging from 81.93% to 97.59% and 78.14 to 85.12%, respectively. As a comparative antigen, a preparation of a Leishmania extract showed sensitivity and specificity values of 75.90% and 74.88%, respectively. The present study was able to identify proteins capable of being used for the serodiagnosis of canine visceral leishmaniasis.

Asunto(s)

RESUMEN

Central nervous system (CNS) infections comprise life-threatening clinical conditions in domestic species, and are commonly related to severe sequelae, disability, or high fatality rates. A set of bacterial pathogens have been identified in central nervous infections in livestock and companion animals, although the most of descriptions are restricted to case reports and a lack of comprehensive studies involving CNS-related bacterial infections have been focused on a great number of domestic species. In this scenario, we retrospectively investigated selected epidemiological data, clinical findings, bacteriological culture, and in vitro susceptibility patterns of 136 nonrepetitive neurologic cases in domestic species (2005-2021). Bacterial isolates were recovered from 25% (34/136) of the cerebrospinal fluid (CSF) sampled. The isolates were obtained from cattle (9/136 = 6.6%), dogs (7/136 = 5.1%), horses (6/136 = 4.4%), goats (3/136 = 2.2%), pigs (3/136 = 2.2%), sheep (3/136 = 2.2%), cats (2/136 = 1.5%), and asinine (1/136 = 0.7%). Among animals with bacterial isolation, Staphylococcus aureus (6/34 = 17.6%), Escherichia coli (5/34 = 14.7%), Staphylococcus beta-hemolytic (5/34 = 14.7%), and Trueperella pyogenes (3/34 = 8.8%) were predominant, in addition to a miscellaneous of other bacteria isolated in minor frequency, e.g., Corynebacterium pseudotuberculosis, Enterobacter cloacae, Mannheimia haemolytica, Pseudomonas aeruginosa, and Streptococcus equi subsp. equi. In vitro susceptibility tests of isolates revealed that amoxicillin/clavulanic acid (11/13 = 84.6%), cephalexin (9/11 = 81.8%), and florfenicol (9/12 = 75%) were the most effective antimicrobials. Conversely, isolates exhibited resistance mainly to tetracycline (6/10 = 60%), penicillin (6/11 = 54.5%), and trimethoprim/sulfamethoxazole (5/11 = 45.5%). Also, multidrug resistance to ≥ 3 classes of antimicrobials was found in 23.5% (8/34) strains. Data relative to the outcome was available in 79.4% (27/34) of animals that had bacterial isolation, and from these, the lethality rate was 92.6% (25/27). Incoordination (14/34 = 41.2%), recumbency (11/34 = 32.4%), apathy (10/34 = 29.4%), anorexia (9/34 = 26.5%), blindness (7/34 = 20.6%), seizure (6/34 = 17.6%), limb paresis (5/34 = 14.7%), head-pressing (4/34 = 11.8%), and nystagmus (3/34 = 8.8%) were the most frequent clinical signs. A variety of bacterial pathogens were identified in the CSF of domestic species showing neurologic signs, with a predominance of staphylococci, streptococci, and enterobacteria. High lethality of cases, poor in vitro efficacy of conventional antimicrobials, and a high in vitro multidrug resistance pattern of isolates were seen. Our results contribute to etiological characterization, antimicrobial resistance patterns, and clinical-epidemiological findings of bacterial infections in domestic species with neurological signs.

Asunto(s)

RESUMEN

In the present study, an immunoproteomic approach using Leishmania infantum parasites isolated from naturally infected dogs from an endemic region of the disease, was carried out to identify new antigens to be used in the diagnosis of canine visceral leishmaniasis (CVL). Protein extracts, obtained from parasites isolated from asymptomatic (CanLA) and symptomatic (CanLS) dogs, were used to perform the two-dimensional gels. Western Blotting assays were carried out by employing a pool of sera from dogs with visceral leishmaniasis (CanLA or CanLS), healthy dogs from an endemic area, or dogs with similar diseases associated with cross-reactions (babesiosis and ehrlichiosis). With these results, it was possible to exclude the spots that showed a cross-reactivity of the sera from groups of healthy dogs, and those with babesiosis or ehrlichiosis. Taken together, 20 proteins were identified, 15 of which have already been described in the literature and 5 of which are hypothetical. An immunogenomic screen strategy was applied to identify conserved linear B-cell epitopes in the identified hypothetical proteins. Two peptides were synthesized and tested in ELISA experiments as a proof of concept for the validation of our immunoproteomics findings. The results demonstrated that the antigens presented sensitivity and specificity values ranging from 81.93% to 97.59% and 78.14 to 85.12%, respectively. As a comparative antigen, a preparation of a Leishmania extract showed sensitivity and specificity values of 75.90% and 74.88%, respectively. The present study was able to identify proteins capable of being used for the serodiagnosis of canine visceral leishmaniasis.

RESUMEN

OBJECTIVE: To verify the effect of foot reflexology on the electrical muscle activity of the lateral and medial gastrocnemius muscle, and to examine the distribution, plantar pressure, and body sway in patients with type 2 diabetes mellitus. METHODS: This pilot randomized controlled trial enrolled 17 volunteers who were clinically diagnosed with diabetes mellitus. The sample was assigned to one of two groups: the control group (CG, n = 7), who received information on foot care and health, and the intervention group (IG, n = 10), who received the application of foot reflexology on specific areas of the feet, for 10 consecutive days. There was blinding of the evaluator and the therapist. Surface electromyography (EMG) was used to assess the electrical activity of the medial and lateral gastrocnemius muscles in maximum voluntary isometric contraction (MVIC) and isotonic contraction (IC); baropodometry and stabilometry were used to analyze unloading, plantar weight distribution, and body sway. RESULTS: There was a statistically significant difference for the variables of maximum peak electrical activity of the left medial gastrocnemius (p = 0.03; effect size = 0.87 and power = 0.81) and left lateral gastrocnemius muscles (p = 0.04, effect size = 0.70 and power = 0.66) respectively, in the intragroup IC, and median frequency of the left medial gastrocnemius muscle in the intragroup MVIC (p = 0.03; effect size = 0.64 and power = 0.59), and in the variables intergroups of the total area on the right side (p = 0.04; effect size = 1.03 and power = 0.50) and forefoot area on the left side (p = 0.02; effect size = 0.51 and power = 0.16). CONCLUSIONS: We conclude that foot reflexology influenced some variables of the intergroup plantar distribution and intragroup EMG in the sample studied. There is a need for a placebo group, a larger sample and a follow-up to strengthen the findings of these experiments.

Asunto(s)

RESUMEN

The present investigation comprised two independent observational arms to evaluate the influence of pre-existing flavivirus humoral immunity and the age-impact on 17DD-YF vaccination immunity. Flavivirus (YFV; DENV; ZIKV) serology and YF-specific cellular immunity was evaluated in 288 children/9Mths-4Yrs and 288 adults/18-49Yrs residents of areas without YFV circulation. Data demonstrated that flavivirus seropositivity at baseline was higher in Adults as compared to Children (26%;87%;67% vs 6%;13%;15%, respectively). The heterologous flavivirus seropositivity (DENV; ZIKV) did not impact the YF-specific cellular immune response at baseline. However, higher levels of NCD4, EMCD8, IFN-MCD8, NCD19 and nCMCD19 were observed in subjects with pre-existing YFV seropositivity. Primary vaccination of YFV-seronegative volunteers led to higher levels of YF-neutralizing antibodies in Adults as compared to Younger Children (9Mths-2Yrs). Although similar seropositivity rates observed amongst Children and Adults at D30-45, lower rates were observed in Younger Children (9Mths-2Yrs) at D365 (94%;95%;100% vs 87%;96%;99%, respectively). A progressive decline in antibody levels were reported at D365, being more expressive in Children as compared to Adults. All age-subgroups exhibited at D30-45 increased levels of eEfCD4, EMCD4, IFN-MCD8 and nCMCD19 together with a decrease of eEfCD8 and CMCD8. While an increase of EMCD8 were observed in all subgroups at D30-45, a declined duration at D365 was reported only in Younger Children (9Mths-2Yrs). Biomarker signatures further support that only Younger Children (9Mths-2Yrs) presented a progressive decline of EMCD8 at D365. Together, these findings demonstrated that regardless the similarities observed in YF-neutralizing antibodies, the age impacts the duration of cellular immune response to primary 17DD-YF vaccination.

Asunto(s)

RESUMEN

Notável é a gama de tratamentos faciais, com intuito estético, com os quais podemos preservar o equilíbrio da forma ou a beleza de nossos pacientes. Preenchimentos, toxina botulínica, laser e outras tecnologias são amplamente demonstrados à classe dermatológica. As pálpebras também podem ser tratadas com esses e outros recursos terapêuticos. No entanto, a herniação das bolsas de gordura das pálpebras superiores não tem resultados significativos com esses métodos. O avanço das técnicas conhecidas como minimamente invasivas e das tecnologias não supre a contento o tratamento desta unidade estética facial. Pensando no rejuvenescimento global da face é improvável conseguirmos um resultado de excelência sem atuar nas pálpebras. A blefaroplastia superior segue insubstituível e é o tratamento de escolha para redundância da pele e herniação das bolsas de gordura. Esta cirurgia, com amplo histórico na Dermatologia, tem um papel único e fundamental no rejuvenescimento facial. Procuramos neste estudo demonstrar a técnica cirúrgica de blefaroplastia superior de maneira didática e comprovar sua eficácia e segurança, com bons resultados estéticos e funcionais. Com pleno conhecimento desta região anatômica e dos preceitos técnicos, reconhecemos poder realizá-la com segurança.

It is noteworthy the range of facial treatments, with aesthetic purpose, with which we can preserve the balance of the shape or beauty of our patients. Fillers, botulinum toxin, laser, and other technologies are widely used in dermatology. Eyelids can also be treated with these and other therapeutic resources. However, herniation of the fat pockets of the upper eyelids does not present significant results with these methods. The advancement of techniques known as minimally invasive and other technologies does not satisfy the treatment of this facial aesthetic unit. Thinking about the global rejuvenation of the face, it is unlikely that we will achieve a result of excellence without acting on the eyelids. Upper blepharoplasty remains irreplaceable, and it is the treatment of choice for skin redundancy and herniation of fat pockets. This surgery, with a long history in Dermatology, has a unique and fundamental role in facial rejuvenation. In this study, we tried to demonstrate the surgical technique of superior blepharoplasty educationally and to prove its efficacy and safety, with good aesthetic and functional results. With full knowledge of this anatomical region and technical precepts, we recognize that we can perform it safely.

RESUMEN

[This corrects the article DOI: 10.3389/fimmu.2019.01211.].

RESUMEN

The present study aims to determine whether 17DD-YF-specific humoral and cellular immunological memory is maintained 8-years after primary vaccination with subdoses (10,447IU;3,013IU;587IU;158IU;31IU). For this purpose, this follow-up study was carried out in a subset of volunteers (n = 98) originally enrolled in the dose-response study in 2009 and 46 non-vaccinated controls. Our results demonstrated that vaccinees, who had seroconverted following primary vaccination and had not been revaccinated, present similar neutralizing antibodies levels and YF-specific cellular memory, particularly CMCD4 and EMCD8 as compared to the reference full dose (27,476IU). Although, PRNT seropositivity rates were similar across subgroups (94, 82, 83, 94, 80, and 91%, correspondingly), only doses above 587IU elicited similar iterative proportion of seropositivity rates, calculated as a progressive decrease on seropositivity rates along time (89, 80, 80, and 91%, respectively) as compared to 158IU and 31IU (68 and 46%, respectively). Noteworthy were the strong positive correlations ("EMCD4,EMCD8" and "TNFCD8,IFNCD8") observed in most subdoses, except for 31IU. Major similarities underscored the preserved antibody titers and the outstanding levels of EMCD8, relevant correlates of protection for YF-specific immunity. These findings provide evidences to support the regular use of dose sparing strategy for YF vaccine in adults.

Asunto(s)

RESUMEN

BACKGROUND: The 17DD-yellow fever (YF) vaccine induces a long-lasting protective immunity, resulting from humoral and cellular immunological memory. The treatment of rheumatoid arthritis (RA) patients with disease-modifying anti-rheumatic drugs (DMARD) may affect pre-existing 17DD-vaccine protective immunity and increase the risk of acquiring YF infection. Our goal was to determine whether DMARD would affect the duration of YF-specific protective immunity in RA patients. METHODS: A total of 122 RA patients, previously immunized with the 17DD-YF vaccine (1-5, 5-9, and ≥ 10 years) and currently under DMARD therapy, were enrolled in the present investigation. Immunomodulatory therapy encompasses the use of conventional synthetic DMARD alone (csDMARD) or combines with biological DMARD (cs+bDMARD). A total of 226 healthy subjects were recruited as a control group (CONT). Neutralizing antibody responses were measured by a plaque-reduction neutralization test (PRNT), and cellular immunity was evaluated by an in vitro 17DD-YF-specific peripheral blood lymphoproliferative assay. RESULTS: The data demonstrated that csDMARD therapy did not affect the duration of protective immunity induced by the 17DD-YF vaccine compared to that of CONT, as both presented a significant time-dependent decline at 10 years after vaccination. Conversely, cs+bDMARD therapy induced a premature depletion in the main determinants of the vaccine protective response, with diminished PRNT seropositivity levels between 5 and 9 years and impaired effector memory in CD8+ T cells as early as 1-5 years after 17DD-YF vaccination. CONCLUSIONS: These findings could support changing the vaccination schedule of this population, with the possibility of a planned booster dose upon the suspension of bDMARD in cases where this is allowed, even before 10 years following 17DD-YF vaccination. The benefit of a planned booster dose should be evaluated in further studies. TRIAL REGISTRATION: RBR-946bv5 . Date of registration: March 05, 2018. Retrospectively registered.

Asunto(s)

RESUMEN

The aim of this work was to evaluate how an aqueous micellar system containing Amphotericin B (AmB) and sodium deoxycholate (DOC) can be rebuilt after heating treatment. Also, a review of the literature on the physicochemical and biological properties of this new system was conducted. Heated (AmB-DOC-H) and unheated (AmB-DOC) micelles were then diluted at four different concentrations (50 mg · L(-1), 5 mg · L(-1), 0.5 mg · L(-1), and 0.05 mg · L(-1)) to perform physicochemical studies and a pharmacotoxicity assay, in which two cell models were used for the in vitro experiments: red blood cells (RBC) from human donors and Candida parapsilosis (Cp). While potassium (K(+)) and hemoglobin leakage from RBC were the parameters used to evaluate acute and chronic toxicity, respectively, the efficacy of AmB-DOC and AmB-DOC-H were assessed by K(+) leakage and cell survival rate from Cp. The spectral study revealed a slight change in the AmB-DOC aggregate peak from 327 nm to 323 nm, which is the peak for AmB-DOC-H. Although AmB-DOC and AmB-DOC-H exhibited different behavior for hemoglobin leakage, AmB-DOC produced higher leakage than AmB-DOC-H at high concentrations (from 5 mg · L(-1)). For K(+) leakage, both AmB-DOC and AmB-DOC-H showed a similar profile for both cell models, RBC and Cp (P < 0.05). AmB-DOC-H and AmB-DOC also revealed a similar profile of activity against Cp with an equivalent survival rate. In short, AmB-DOC-H showed much less toxicity than AmB-DOC, but remained as active as AmB-DOC against fungal cells. The results highlight the importance of this new procedure as a simple, inexpensive, and safe way to produce a new kind of micelle system for the treatment of systemic fungal infections.

Asunto(s)

RESUMEN

Clinical involvement of the nervous system in visceral larva migrans due to Toxocara is rare, although in experimental animals the larvae frequently migrate to the brain. A review of the literature from the early 50's to date found 29 cases of brain involvement in toxocariasis. In 20 cases, various clinical and laboratory manifestations of eosinophilic meningitis, encephalitis, myelitis or radiculopathy were reported. We report two children with neurological manifestations, in which there was cerebrospinal fluid pleocytosis with marked eosinophilia and a positive serology for Toxocara both in serum and CSF. Serology for Schistosoma mansoni, Cysticercus cellulosae, Toxoplasma and cytomegalovirus were negative in CSF, that was sterile in both cases. Improvement of signs and symptoms after specific treatment (albendazole or thiabendazole) was observed in the two cases. A summary of data described in the 25 cases previously reported is presented and we conclude that in cases of encephalitis and myelitis with cerebrospinal fluid pleocytosis and eosinophilia, parasitic infection of the central nervous system should be suspected and serology should be performed to establish the correct diagnosis and treatment.

Asunto(s)

RESUMEN

Envolvimento do sistema nervoso, com manifestações clínicas, na infecção pelo Toxocara é raro, embora, nos modelos experimentais a larva freqüentemente se localize no sistema nervoso central. Uma revisão da literatura a partir de 1956, quando a síndrome foi descrita, até 2002, mostrou a publicação de 29 casos de neurotoxocaríase, dos quais em 20 havia relato de alterações clínicas e laboratoriais indicativas de meningite, ou encefalite, ou mielite ou radiculite eosinofílicas. Nessa comunicação estamos relatando observações em duas crianças que apresentaram sinais e sintomas neurológicos, com pleocitose e eosinofilia acentuada no líquor e com sorologia positiva para Toxocara no soro e no liquor. Sorologia para Schistosoma mansoni, Cysticercus cellulosae, Toxoplasma e citomegalovirus foram negativas no liquor, que era estéril nos dois casos. Houve melhora dos sinais e sintomas após o tratamento específico (albendazol e tiabendazol) nos dois casos. É apresentado um sumário dos principais achados nos casos relatados na literatura e se conclue que em casos de meningite, encefalite ou mielite com líquor apresentando pleocitose com eosinofilia acentuada, a suspeita de infecção parasitária deve ser levantada, sendo necessário sorologia especifica para diagnóstico e tratamento adequados.

Asunto(s)