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BACKGROUND: Antibody-mediated rejection following liver transplantation (LT) has been increasingly recognized, particularly with respect to the emergence of de novo donor-specific antibodies (DSAs) and their impact on graft longevity. While substantial evidence for adult populations exists, research focusing on pediatric LT outcomes remains limited. AIM: To investigate the prevalence of human leukocyte antigen (HLA) mismatches and DSA and evaluate their association with rejection episodes after pediatric LT. METHODS: A cohort of pediatric LT recipients underwent HLA testing at Santa Casa de Porto Alegre, Brazil, between December 2013 and December 2023. Only patients who survived for > 30 days after LT with at least one DSA analysis were included. DSA classes I and II and cross-matches were analyzed. The presence of de novo DSA (dnDSA) was evaluated at least 3 months after LT using the Luminex® single antigen bead method, with a positive reaction threshold set at 1000 MFI. Rejection episodes were confirmed by liver biopsy. RESULTS: Overall, 67 transplanted children were analyzed; 61 received grafts from living donors, 85% of whom were related to recipients. Pre-transplant DSA (class I or II) was detected in 28.3% of patients, and dnDSA was detected in 48.4%. The median time to DSA detection after LT was 19.7 [interquartile range (IQR): 4.3-35.6] months. Biopsy-proven rejection occurred in 13 patients at follow-up, with C4d positivity observed in 5/13 Liver biopsies. The median time to rejection was 7.8 (IQR: 5.7-12.8) months. The presence of dnDSA was significantly associated with rejection (36% vs 3%, P < 0.001). The rejection-free survival rates at 12 and 24 months were 76% vs 100% and 58% vs 95% for patients with dnDSA anti-DQ vs those without, respectively. CONCLUSION: Our findings highlight the importance of incorporating DSA assessment into pre- and post-transplantation protocols for pediatric LT recipients. Future implications may include immunosuppression minimization strategies based on this analysis in pediatric LT recipients.
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Rechazo de Injerto , Supervivencia de Injerto , Antígenos HLA , Prueba de Histocompatibilidad , Isoanticuerpos , Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Masculino , Rechazo de Injerto/inmunología , Rechazo de Injerto/epidemiología , Femenino , Niño , Antígenos HLA/inmunología , Isoanticuerpos/sangre , Isoanticuerpos/inmunología , Brasil/epidemiología , Preescolar , Supervivencia de Injerto/inmunología , Prueba de Histocompatibilidad/métodos , Incidencia , Lactante , Adolescente , Hígado/inmunología , Hígado/patología , Biopsia , Estudios Retrospectivos , Donadores Vivos , Receptores de Trasplantes/estadística & datos numéricosRESUMEN
BACKGROUND: Breast cancer is one of the most lethal diseases affecting women globally. Its progression is influenced by various factors, including the immune system's ability to combat cancer cells. While hematological indices have been recognized as valuable biomarkers for monitoring patients with different types of neoplasms, there remains a considerable gap in research concerning their application in breast cancer. MATERIAL AND METHODS: To address this, we conducted a systematic review of studies examining hematological indices as prognostic predictors in breast cancer patients. RESULTS: The majority of studies demonstrate a significant correlation between these indices and survival outcomes, underscoring their potential utility in patient monitoring. CONCLUSIONS: Hematological-based indexes can be valuable tools for monitoring breast cancer, especially those ongoing poor prognosis scenarios.
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Thyroid hormones influence mammary gland differentiation and lactation by binding to thyroid hormone receptors. Hyperthyroidism disrupts pregnancy and lactation, affecting offspring growth and milk production. Despite maternal milk is a vital source of bioactive compounds and nutrients for newborns, it is unclear whether hyperthyroidism alters its composition, mainly immune factors. Therefore, our work aimed to evaluate the influence of hyperthyroidism on milk quality and immunological parameters during early lactation. Twelve-week-old female Wistar rats received daily injections of 0,25 mg/kg T4 (HyperT, n = 20) or vehicle (control, n = 19) starting 8 days before mating and continuing throughout pregnancy. Rats were euthanized on day 2 of lactation for analyzing the impact of hyperthyroidism on mammary gland, serum and milk samples. HyperT pups exhibited reduced weight, length and head circumference with altered serum hormones, glucose and albumin levels. HyperT mammary gland analysis revealed structural changes, including decreased alveolar area, adipose tissue, increased connective tissue and reduced epithelial elongation, accompanied by decreased TRß1 RNA expression. HyperT milk displayed lower caloric value and fat concentration. HyperT animals exhibited altered milk immune cell counts, displaying increased numbers of CD45+ and CD3+ cells and decreased CD11b/c+ cells without changes on milk and serum IgA, IgG and IgG2a levels. In summary, we have demonstrated that hyperthyroidism affects mammary gland morphology, disrupts pup development and alters biochemical and immunological parameters. Our findings highlight the impact of maternal hyperthyroidism on offspring early development and milk immune composition, underscoring the importance of thyroid function in maternal and neonatal immune health.
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Hipertiroidismo , Lactancia , Glándulas Mamarias Animales , Leche , Ratas Wistar , Animales , Femenino , Hipertiroidismo/inducido químicamente , Hipertiroidismo/patología , Hipertiroidismo/metabolismo , Glándulas Mamarias Animales/metabolismo , Glándulas Mamarias Animales/efectos de los fármacos , Glándulas Mamarias Animales/patología , Glándulas Mamarias Animales/crecimiento & desarrollo , Ratas , Inmunoglobulinas/sangre , Inmunoglobulinas/metabolismo , Embarazo , Hormonas Tiroideas/sangre , Hormonas Tiroideas/metabolismoRESUMEN
Leukocyte- and platelet-rich fibrin (L-PRF), a by-product of centrifuged autologous whole blood, contains high concentrations of platelets, leukocytes, and fibrin (the latter spontaneously creating a strong 3-D network (a membrane)). L-PRF membranes possess several characteristics essential in wound healing, including a barrier function, an antibacterial and analgesic activity, and the release of growth factors enhancing tissue regeneration and neo-vasculogenesis. This review investigated the role of L-PRF in treating non-responding chronic wounds such as diabetic foot, venous leg ulcers, pressure ulcers, complex wounds, leprosy ulcers (Hansen's Disease), and other demanding wounds. Chronic wounds affect millions worldwide, negatively impacting their quality of life, productivity, and life expectancy while incurring high treatment costs for themselves and private and public health systems. L-PRF has demonstrated clear adjunctive advantages in treating chronic skin wounds, shortening the time to complete wound closure, and improving patient-reported outcome measures (including reducing pain and minimizing the need for analgesics). Also, in other demanding wounds, L-PRF facilitates healing. To help clinicians, this article also proposes recommendations for the use of L-PRF in the treatment of extra-oral wounds.
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This study assessed qualitative and quantitative leukocyte evaluation as potential broiler chicken welfare indicators, contributing to the limited literature on white blood cell (WBC) morphology as a diagnostic tool for welfare. Broiler chicken welfare within four poultry houses (PH) 1 to 4, each on a different farm, was assessed using on-field indicators of affective states and health, and WBC morphology was examined. Affective states were evaluated using the Qualitative Behavior Assessment (QBA), with 25 behavioral expressions scored on a visual analogue scale (VAS) and grouped into two categories. Health indicators included assessments of lameness, footpad dermatitis, dermatitis on the breast and abdominal areas, hock burn, and feather cleaning. Blood samples were collected, differential leukocyte counts were performed, and a cell score was created for the recognition, classification, and interpretation of morphologic diversity of heterophils and lymphocytes. The heterophil to lymphocyte ratio (H/L) was also determined. Descriptive statistics and generalized linear models for binomial responses were used to analyze the results. PH4 differed from the other farms, showing a higher frequency of birds within QBA group 1 ('Attentive'to 'Desperate'), while birds in PH1, PH2, and PH3 were more frequent in QBA group 2 ('Relaxed' to 'Positively occupied'). Elevated proportions of heterophils in birds from PH4 (0.61, CI95%: 0.58; 0.64) and PH3 (0.60, CI95%: 0.57; 0.63) suggested higher stress levels and inflammatory responses. Birds in PH2 and PH4 exhibited higher frequencies of health issues such as dermatitis and lameness, and higher proportions of abnormalities in WBC number and morphology. PH3 and PH4 exhibited higher H/L ratios of 3.03 and 2.58, respectively, consistent with the on-field health and behavioral indicators. Blood samples from birds in PH2 and PH4 showed a proportion of 90% toxic change in heterophils, while in PH1 and PH3 it was 70%, indicating high levels of abnormal WBC morphology across all PHs. The findings emphasize the multifactorial nature of welfare impairments, including environmental conditions, health, and affective states. This highlights the need for indicators that reflect multiple welfare impacts, such as WBC counts and morphological alterations, which can serve as powerful tools in the complex task of assessing animal welfare.
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AIMS: To investigate the SARS-CoV-2 Spike protein (Spk)-induced inflammatory response and its downmodulation by diminazene aceturate (DIZE). MATERIALS AND METHODS: Through inducing Spk inflammation in murine models, leukocyte migration to the peritoneum, levels of myeloperoxidase (MPO), malondialdehyde (MDA), rolling and adhesion of mesenteric leukocytes, and vascular permeability were investigated. Extracellular DNA traps (DETs) induced by Spk and the production of IL-6 and TNF-α were analyzed using human neutrophils, monocytes, and macrophages. In silico assays assessed the molecular interaction between DIZE and molecules related to leukocyte migration and DETs induction. KEY FINDINGS: Spk triggered acute inflammation, demonstrated by increasing leukocyte migration. Oxidative stress was evidenced by elevated levels of MPO and MDA in the peritoneal liquid. DIZE attenuated cell migration, rolling, and leukocyte adhesion, improved vascular barrier function, mitigated DETs, and reduced the production of Spk-induced pro-inflammatory cytokines. Computational studies supported our findings, showing the molecular interaction of DIZE with targets such as ß2 integrin, PI3K, and PAD2 due to its intermolecular coupling. SIGNIFICANCE: Our results outline a novel role of DIZE as a potential therapeutic agent for mitigating Spk-induced inflammation.
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COVID-19 , Movimiento Celular , Diminazeno , Trampas Extracelulares , Inflamación , Leucocitos , SARS-CoV-2 , Diminazeno/farmacología , Diminazeno/análogos & derivados , Animales , Ratones , Humanos , Movimiento Celular/efectos de los fármacos , Trampas Extracelulares/metabolismo , Trampas Extracelulares/efectos de los fármacos , Leucocitos/metabolismo , Leucocitos/efectos de los fármacos , SARS-CoV-2/efectos de los fármacos , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , COVID-19/metabolismo , Masculino , Tratamiento Farmacológico de COVID-19 , Adhesión Celular/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Glicoproteína de la Espiga del CoronavirusRESUMEN
Reptile white blood cell (WBC) morphological features are strikingly variable across species. In the Argentine black and white tegu (Salvator merianae), red tegu (Salvator rufescens), and Savannah monitor (Varanus exanthematicus), previous reports described a WBC type with a single distinct, clear, linear- to ovoid- to crescent-shaped inclusion of presumptive monocytic origin. The objective of this study was to further investigate the origin of this unique WBC type with crescent-shaped inclusions. Blood samples from two Argentine black and white tegus, tegu 1, a 4-year-old female, and tegu 2, a 2-year-old presumed male, were submitted for routine hematological evaluation. Additional blood films were prepared and stained with these cytochemical stains: alkaline phosphatase (ALP; naphthol AS-MX phosphate substrate), alpha-naphthyl butyrate esterase, alpha-chloroacetate esterase, myeloperoxidase, Periodic acid-Schiff, and Sudan black B. Blood films from tegu 1 were also stained with a second ALP stain (5-bromo-4-chloro-3-indoxyl-phosphate and nitroblue tetrazolium substrate), Luna, luxol fast blue, and toluidine blue. The blood from tegu 1 was cytocentrifuged to isolate and fix the buffy coat in glutaraldehyde 2.5% aqueous solution for transmission electron microscopy. Six morphologically distinct WBC types were identified from tegu 1, including heterophils, basophils, monocytes, azurophils, lymphocytes, and the unique WBC type, which were identified as eosinophils with inclusions. WBC types in tegu 2 were similar; however, eosinophils lacked a discernable inclusion. Proper WBC identification will be useful in obtaining accurate hemogram data for this species.
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Blood count is crucial for assessing bone marrow's cell production and differentiation during infections, gaging disease severity, and monitoring therapeutic responses. The profile of blood count in chronic forms of paracoccidioidomycosis (PCM) has been insufficiently explored. To better understand the changes in hematological cells in different stages of the PCM chronic form, we evaluated the blood count, including immature blood cells in automated equipment, before and during the treatment follow-up of 62 chronic PCM patients. Predominantly male (96.8%) with an average age of 54.3 (standard deviation SD 6.9) years, participants exhibited pre-treatment conditions such as anemia (45.2%), monocytosis (38.7%), and leukocytosis (17.7%), which became less frequent after clinical cure. Anemia was more prevalent in severe cases. Notably, hemoglobin and reticulocyte hemoglobin content increased, while leukocytes, monocytes, neutrophils, immature granulocytes, and platelets decreased. Chronic PCM induced manageable hematological abnormalities, mainly in the red blood series. Monocytosis, indicating monocytes' role in PCM's immune response, was frequent. Post-treatment, especially after achieving clinical cure, significant improvements were observed in various hematological indices, including immature granulocytes and reticulocyte hemoglobin content, underscoring the impact of infection on these parameters.
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Many molecular mechanisms that lead to the host antibody response to COVID-19 vaccines remain largely unknown. In this study, we used serum antibody detection combined with whole blood RNA-based transcriptome analysis to investigate variability in vaccine response in healthy recipients of a booster (third) dose schedule of the mRNA BNT162b2 vaccine against COVID-19. The cohort was divided into two groups: (1) low-stable individuals, with antibody concentration anti-SARS-CoV IgG S1 below 0.4 percentile at 180 days after boosting vaccination; and (2) high-stable individuals, with antibody values greater than 0.6 percentile of the range in the same period (median 9525 [185-80,000] AU/mL). Differential gene expression, expressed single nucleotide variants and insertions/deletions, differential splicing events, and allelic imbalance were explored to broaden our understanding of the immune response sustenance. Our analysis revealed a differential expression of genes with immunological functions in individuals with low antibody titers, compared to those with higher antibody titers, underscoring the fundamental importance of the innate immune response for boosting immunity. Our findings also provide new insights into the determinants of the immune response variability to the SARS-CoV-2 mRNA vaccine booster, highlighting the significance of differential splicing regulatory mechanisms, mainly concerning HLA alleles, in delineating vaccine immunogenicity.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , SARS-CoV-2/genética , Vacuna BNT162 , Vacunas de ARNm , COVID-19/prevención & control , Anticuerpos , Inmunidad Innata , Anticuerpos AntiviralesRESUMEN
OBJECTIVE: This study aimed to establish the association between HLA-A, B, DR genotypes and gastrointestinal variables in patients with SpA without inflammatory bowel disease (IBD). METHODS: Retrospective study of 91 patients with SpA and 401 healthy controls, with typing by Illumina Sequencing/PacBio and LIFECODES HLA-PCR/SSO multiplex sequencing technology. The presence of gastrointestinal symptoms was evaluated by administering a survey, and those who presented 2 or more symptoms were taken for clinical evaluation by rheumatology and gastroenterology, colonoscopy and histopathological study. (Ethics committee approval). RESULTS: The 59,3% of the patients were men, with a mean age of 43,9±11.4 years; 80,2% were classified as ankylosing spondylitis. 14, 28 and 19 genotypes for the HLA-A*, HLA-B* and HLA-DR* loci were identified in both groups, of which a relationship with gastrointestinal symptoms was identified: A*26, A*29 and B*27 were associated to abdominal pain, DRB1*11 and DRB1*16 with abdominal distention, A*30, B*38, DRB1*13 and DRB1*14 with weight loss, B*40 with diarrhea >4 weeks, and presence of mucus in the stools with A*02 and DRB1*11 (p<0.05). Furthermore, the presence of B*15 had a statistical relationship with intolerance to some food, highlighting the B*27 genotype in relation to grains and dairy products, A*23 with grains, vegetables and meats, and B*49 with vegetables and dairy (p<0.05). Regarding the endoscopic variables, macroscopic changes were found in the ileum mucosa related to A*02, B*48, DRB1*14 and the relationship between B*27 and ulcers at this level should be highlighted. Macroscopic changes in the sigmoid colon with B*48 and the rectum with A*30. In microscopic changes, inflammatory alterations of the ileum are mentioned with genotypes DRB1*07, DRB1*13 and DRB1*14, a genotype that is related to changes in the ileum both endoscopically and histologically (p<0.05). CONCLUSIONS: These findings indicate a potential genetic predisposition related to HLA genotypes that may increase the likelihood of food intolerance, gastrointestinal symptoms, and even visible and microscopic changes, specifically in the ileal tissue. The study highlights the presence of B*27 and other noteworthy HLA class I and class II genes (such as DRB1*14) in the diverse Colombian population.
OBJETIVO: Establecer la asociación entre genotipos HLA-A, B, DR y variables gastrointestinales en pacientes con EspA, sin enfermedad inflamatoria intestinal (EII). MÉTODOS: Estudio retrospectivo de 91 pacientes con EspA y 401 controles sanos, con tipificación por tecnología de secuenciación Illumina Sequencing/PacBio, y LIFECODES HLA-PCR/SSO multiplex. Se evaluó la presencia de síntomas gastrointestinales por aplicación de una encuesta, y, aquellos que presentaran dos o más síntomas, fueron llevados a valoración clínica por reumatología y gastroenterología, colonoscopia y estudio histopatológico. (Aprobación del Comité de Ética, HMC, 2022 - 2020). RESULTADOS: El 59,3% de los pacientes fueron hombres, con edad media de 43,9 ± 11,4 años. El 80,2% se clasificó como espondilitis anquilosante. Se identificaron en ambos grupos 14, 28 y 19 genotipos para los loci HLA-A*, HLA-B* y HLA-DR*, de los cuales se identificó relación con síntomas gastrointestinales: A*26, A*29 y B*27, con dolor abdominal; DRB1*11 y DRB1*16, con distensión abdominal; A*30, B*38, DRB1*13 y DRB1*14, con pérdida de peso; B*40, con diarrea >4 semanas y presencia de moco en las deposiciones con A*2 y DRB1*11 (p<0,05). Además, la presencia de B*15, tuvo relación estadística con intolerancia a algún tipo de alimento, a resaltar el genotipo B*27, en relación con granos y lácteos; A*23 con granos, verduras y carnes; y el B*49, con verduras y lácteos (p<0,05). Frente a las variables endoscópicas, se encontraron cambios macroscópicos en la mucosa de íleon relacionados con A*02, B*48, DRB1*14 y, a destacar, la relación B*27 con úlceras a este nivel. Cambios macroscópicos en colon sigmoides con B*48 y en recto con A*30. En cambios microscópicos, se mencionan alteraciones inflamatorias de íleon con genotipos DRB1*07, DRB1*13 y DRB1*14, genotipos que se relaciona a cambios en íleon tanto endoscópica e histológicamente (p<0,05). CONCLUSIONES: Estos resultados sugieren una posible susceptibilidad genética asociada al HLA, con genotipos que pueden predisponer a intolerancia alimentaria, síntomas gastrointestinales, e incluso, a cambios macroscópicos e histológicos, particularmente en tejido de íleon, entre los cuales está presente el B*27, pero resaltan otros interesantes en HLA clase I, como clase II (DRB1*14), en una población de alto mestizaje como la colombiana.
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Enfermedades Gastrointestinales , Genotipo , Espondiloartritis , Humanos , Masculino , Femenino , Adulto , Estudios Retrospectivos , Enfermedades Gastrointestinales/genética , Enfermedades Gastrointestinales/etiología , Espondiloartritis/genética , Espondiloartritis/complicaciones , Persona de Mediana Edad , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/complicaciones , Antígenos HLA/genética , Antígenos HLA-A/genética , Antígenos HLA-B/genéticaRESUMEN
OBJECTIVE: The objective is to describe the HLA allelic frequency in PsA and correlate it with demographic and clinical variables. METHODS: Retrospective study of adult patients with a diagnosis of PsA (n=23) and healthy controls (n=46), all with a request for HLA-A, B, C, DR. Typing was performed using HLA-PCR/SSO LifeCodes and analyzed on the LUMINEX IS100/200 xMAP® system. (Ethics/Code HMC2022-014). RESULTS: One hundred thirty-eight alleles were included from 69 individuals, 43,5% women, aged 44,5±16,5 years in patients with PsA, with a mean age of disease onset of 33.4±14 years. Only 9.5% had a high Body Mass Index and dyslipidemia was the most frequent comorbidity (34.8%), followed by high blood pressure (26,1%). 82% debuted with skin manifestation and once the joint disease was established, the predominance was peripheral (74%) due to arthritis/arthralgia in 74%, enthesitis in 30% and dactylitis in 13%. The allele frequencies were for HLA*A 2402 (13%), 3201 (13%) and 2427 (8,7%), for HLA*B 1402 (17,4%), 4002 (17,4%), 3801 (13%) and HLA*DR 0404 (17,4%), 0407 (13%). No HLA*B27 was identified and HLA*C0602 was only 2,2%. HLA A*0201 and DR*1301 were less frequent in controls versus PsA (p=0.024 and 0,029, respectively), while HLA*B1302 was frequent in PsA (p=0,035). CONCLUSIONS: Curiously, there were no positive results for HLAB*27, which may be related to the population mix. HLA Cw6 is traditionally associated with psoriasis. However, its absence has been linked to nail disorders and PsA; consequently, in our study, it had a low frequency (2,2%). On the other hand, HLA*B1302 has been related to the disease and its early onset; in the healthy Colombian population, it has been described in 0,92%; in our group, it is found to be significant in patients without establishing a clinical association. Few previous studies report HLA results in PsA in Colombia.
OBJETIVO: Describir la frecuencia alélica de HLA en APs y asociarlo con variables demográficas y clínicas. MÉTODOS: Estudio retrospectivo de pacientes adultos con diagnóstico de APs (n=23), y controles sanos (n=46), todos con solicitud de HLA-A, B, C y DR. La tipificación se realizó por medio de HLA-PCR/SSO LifeCodes, y se analizó en el sistema LUMINEX IS 100/200 xMAP®. (Ética/Código HMC2022-014). RESULTADOS: Se incluyeron 138 alelos de 69 individuos, 43,5% mujeres, con edad 44,5±16,5 años, en pacientes con APs, con edad media de inicio de la enfermedad de 33,4±14 años. Solo el 9,5% tuvo Índice de Masa Corporal alto y la dislipidemia fue la comorbilidad más frecuente (34,8%), seguida de hipertensión arterial (26,1%). El 82% debutó con manifestación en piel y una vez establecida la enfermedad articular, el predominio fue periférico (74%), por artritis/artralgias en un 74%, entesitis en 30%, y dactilitis 13%. Las frecuencias alélicas fueron para HLA*A 2402 (13%), 3201 (13%) y 2427 (8,7%), para HLA*B 1402 (17,4%), 4002 (17,4%), 3801 (13%) y HLA*DR 0404 (17,4%), 0407 (13%). No se identificó HLA*B27 y HLA*C0602 fue solo del 2,2 %. HLA A*0201 y DR*1301 fueron menos frecuentes en controles versus APs (p=0,024 y 0,029, respectivamente), mientras que HLA*B1302 frecuente en APs (p=0,035). CONCLUSIÓN: Curiosamente no hubo resultados positivos para HLAB*27 y esto puede relacionarse con el mestizaje de la población. HLA Cw6 es tradicionalmente asociado a psoriasis, sin embargo, su ausencia se ha relacionado con mayor reporte de alteraciones ungueales y Aps; como consecuencia, en nuestro estudio tuvo una baja frecuencia (2,2%). Por otro lado, el HLA*B1302 ha tenido relación con la enfermedad y su inicio temprano, en población sana colombiana se ha descrito en 0,92%, en nuestro grupo se encuentra de manera significativa en los pacientes sin establecerse asociación clínica. Pocos estudios previos refieren resultados de HLA en APs en Colombia.
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Alelos , Artritis Psoriásica , Frecuencia de los Genes , Humanos , Femenino , Masculino , Colombia , Adulto , Artritis Psoriásica/genética , Artritis Psoriásica/diagnóstico , Estudios Retrospectivos , Persona de Mediana Edad , Antígenos HLA/genéticaRESUMEN
In recent years, extensive research has delved into the pathophysiology of local reactions triggered by Bothrops snake venoms. Even though antivenom works well at reducing death and systemic effects, it is still not very effective in treating local reactions because it cannot counteract damage that has already been triggered. This limitation might be attributed to certain molecules that amplify the venom-induced innate response. While evidence suggests endogenous mediators at the venom site play a role in this envenomation, in Brazil, the concurrent use of anti-inflammatory agents or other drugs alongside antivenom remains uncommon. This study evaluated the pharmacological mediation of alterations in leukocyte-endothelium interactions following the experimental envenomation of mice with Bothrops jararaca venom, the main culprit of snake-related accidents in Southeast Brazil. We treated envenomed mice with inhibitors of different pharmacological pathways and observed the cremaster muscle microcirculation with intravital microscopy. We found that eicosanoids related to cyclooxygenase pathways and nitric oxide significantly contributed to B. jararaca venom-induced alterations in leukocyte-endothelium interactions. Conversely, lipoxygenase-mediated eicosanoids, histamine, and serotonin had minimal participation. Notably, dexamethasone and antivenom treatment diminished B. jararaca venom-induced alterations in leukocyte-endothelium interactions. The limited efficacy of the antivenom in managing Bothrops venom-induced local reactions emphasizes the critical need for supplementary treatments to enhance therapeutic outcomes.
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Leukocyte and Platelet-Rich Fibrin (L-PRF) is part of the second generation of platelet-concentrates. L-PRF derived from nonsmokers has been used in surgical procedures, with its beneficial effects in wound healing being proven to stimulate biological activities such as cell proliferation, angiogenesis, and differentiation. Cigarette smoking exerts detrimental effects on tissue healing and is associated with post-surgical complications; however, evidence about the biological effects of L-PRF derived from smokers is limited. This study evaluated the impact of L-PRF secretome (LPRFS) derived from smokers and nonsmokers on angiogenesis and osteoblast differentiation. LPRFS was obtained by submerging L-PRF membranes derived from smokers or nonsmokers in culture media and was used to treat endothelial cells (HUVEC) or SaOs-2 cells. Angiogenesis was evaluated by tubule formation assay, while osteoblast differentiation was observed by alkaline phosphatase and osterix protein levels, as well as in vitro mineralization. LPRFS treatments increased angiogenesis, alkaline phosphatase, and osterix levels. Treatment with 50% of LPRFS derived from smokers and nonsmokers in the presence of osteogenic factors stimulates in vitro mineralization significantly. Nevertheless, differences between LPRFS derived from smokers and nonsmokers were not found. Both LPRFS stimulated angiogenesis and osteoblast differentiation in vitro; however, clinical studies are required to determine the beneficial effect of LPRFS in smokers.
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Systemic lupus erythematosus (SLE) is an autoimmune disorder that impacts connective tissue and can affect various organs and systems within the body. One important aspect of this disease is the role of the human leukocyte antigen (HLA) system, a protein complex that plays a role in the immune response. Specifically, the HLA-DRB1 and HLA-DQB1 genes have been implicated in the development of SLE. In order to better understand this relationship in the Guatemalan population, a study was conducted with the objective of characterizing the allelic and haplotype profiles of the HLA-DQB1 and HLA-DRB1 loci in 50 patients diagnosed with SLE who were receiving treatment at a hospital in Guatemala. Allele and haplotype frequencies were determined and compared to 127 healthy Guatemalan subjects as a control group. The results of the analysis showed a reduction in the frequencies of HLA-DQB1*03 and HLA-DRB1*14 in SLE patients, which could suggest a protective effect on the development of the disease. In contrast, a risk association was found between HLA-DRB1*07, HLA-DRB1*08, HLA-DQB1*02 and HLA-DQB1*06 in SLE patients. Finally, we observed an additional protective associated of haplotype HLA-DRB1*04â¼DQB1*03 with SLE patients, while haplotypes HLA-DRB1*07â¼DQB1*02 and DRB1*08-DQB1*06 showed a risk association.
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Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Cadenas beta de HLA-DQ , Cadenas HLA-DRB1 , Haplotipos , Lupus Eritematoso Sistémico , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Alelos , Estudios de Casos y Controles , Estudios de Asociación Genética , Genotipo , Guatemala , Cadenas beta de HLA-DQ/genética , Cadenas HLA-DRB1/genética , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/diagnósticoRESUMEN
Leukocyte infiltration into the maternal-fetal interface is a consequence of the robust inflammation in the gestational tissues during term labor and preterm labor with or without infection. During pregnancy, the fetal membranes act as a physical barrier that isolates the fetus into the amniotic cavity, keeping it in an optimal environment for its development. In addition, the fetal membranes possess immunological competencies such as the secretion of cytokines and chemokines in response to different stimuli. Clinical and experimental evidence indicates that these tissues are involved in the extensive chemotaxis of immune cells in normal or pathological conditions.Few studies have evaluated the chemotactic capacities of the fetal membranes considering that this tissue is composed of two adjacent tissues, the amnion and the chorion, which have different characteristics. Although these tissues function as a unit, their response is complex since there is an interaction between them, where each tissue contributes differently. The protocol described here allows us to evaluate the in vitro chemotactic capacities of fetal membranes in response to various applied stimuli, considering the contribution of each of their components (amnion and choriodecidua) using a Boyden chamber assay and phenotyping the chemo-attracted leukocytes by flow cytometry.
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Membranas Extraembrionarias , Trabajo de Parto , Embarazo , Recién Nacido , Femenino , Humanos , Amnios , Corion , Quimiotaxis de LeucocitoRESUMEN
Introducción: La medicina regenerativa y terapia celular representa una alternativa segura y eficaz en la regeneración hística. La fibrina rica en plaquetas y leucocitos favorece la cicatrización de la base craneal, con una disminución significativa en las complicaciones, en especial la fístula de líquido cefalorraquídeo. Objetivo: Describir los resultados del empleo de la fibrina rica en plaquetas y leucocitos como elemento accesorio en la reparación de la base craneal. Métodos: Se realizó un estudio descriptivo, transversal en 250 pacientes en el Hospital Hermanos Ameijeiras, operados por procedimientos endonasales endoscópicos con diversos tumores de la base craneal, en los cuales se empleó la fibrina rica en plaquetas y leucocitos durante la fase de reconstrucción. Se realizó una evaluación de la barra de reparación y las complicaciones presentes. Para el análisis de los datos se utilizaron frecuencias absolutas y relativas como medidas resumen. Resultados: El 97,2 % de las barreras de reparación fue catalogada de óptima. Se reporta con el uso de la fibrina rica en plaquetas y leucocitos 2,0 % de fístula de líquido cefalorraquídeo, 0,8 % de infección del sistema nervioso central, 4,0 % de costras nasales posoperatorias. Conclusiones: El presente estudio evidencia el efecto positivo del empleo de la fibrina rica en plaquetas y leucocitos en la reparación del base craneal con gran impacto en el índice de fístula de líquido cefalorraquídeo y la calidad de vida nasosinusal.
Introduction: Regenerative medicine and cell therapy represents a safe and effective alternative in tissue regeneration. Fibrin rich in platelets and leukocytes promotes healing of the cranial base, with a significant decrease in complications, especially cerebrospinal fluid leak. Objective: Describe the results of using fibrin rich in platelets and leukocytes as an accessory element in the repair of the cranial base. Methods: A descriptive, cross-sectional study was carried out in 250 patients at the "Hermanos Ameijeiras" Hospital operated by endoscopic endonasal procedures with various tumors of the cranial base, in which fibrin rich in platelets and leukocytes was used during the reconstruction phase. An evaluation of the repair bar and the complications present was performed. For data analysis, absolute and relative frequencies were used as summary measures. Results: 97.2% of the repair barriers were classified as optimal. With the use of fibrin rich in platelets and leukocytes, 2.0% of cerebrospinal fluid leak, 0.8% of central nervous system infection, 4.0% of postoperative nasal scabs are reported. Conclusions: The present study evidences the positive effect of the use of leukocyte-platelet-rich fibrin in the repair of the skull cranial base, with great impact on the rate of cerebrospinal fluid leak and sinonasal quality of life.
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Polycystic ovary syndrome (PCOS) is a multifactorial disorder and obesity occurs in 38% to 88% of these women. Although hyperandrogenism may contribute to telomere lengthening, increased body mass index (BMI) is associated with telomere erosion. We sought to compare leukocyte telomere length (LTL) in PCOS women with normal, overweight, and obese BMI. We evaluated the relationship between LTL and clinical variables of PCOS and inflammatory biomarkers independent of BMI. A total of 348 women (243 PCOS and 105 non-PCOS) were evaluated for anthropometric measures, total testosterone, androstenedione, estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), free androgen index (FAI), fasting insulin and glycemia, lipid profile, homocysteine, C-reactive protein (CRP) and homeostatic model of insulin resistance (HOMA-IR). LTL was measured by qPCR. The PCOS group presented higher weight, waist circumference, BMI, testosterone, LH, fasting insulin, FAI, and HOMA-IR, and lower E2, SHBG, and fasting glycemia measures compared with the non-PCOS. When stratified by BMI, LTL was increased in all subgroups in PCOS compared to non-PCOS. However, in the PCOS group, LTL was lower in overweight (P = 0.0187) and obese (P = 0.0018) compared to normal-weight women. The generalized linear model showed that BMI, androstenedione, homocysteine, and CRP were associated with telomere biology. Women with PCOS had longer LTL, however, overweight or obesity progressively contributes to telomere shortening and may affect reproductive outcomes of PCOS, while androstenedione may increase LTL.
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Índice de Masa Corporal , Obesidad , Síndrome del Ovario Poliquístico , Acortamiento del Telómero , Humanos , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/metabolismo , Femenino , Obesidad/genética , Obesidad/sangre , Adulto , Adulto Joven , Resistencia a la Insulina , Telómero/metabolismo , Leucocitos/metabolismo , Biomarcadores/sangreRESUMEN
Zinc (Zn) is an essential micronutrient that plays a crucial role in fish development and physiology. This study aimed to evaluate the effects on growth and health in Nile tilapia (Oreochromis niloticus) supplemented with graded levels of zinc amino acid complex (Zn-AA) and subjected to transport stress. Nile tilapia (21.78 ± 0.17 g; (n = 12 fish per tank; stocking density of 1.045 kg- 3) were fed with 0, 25, 50, 75, or 100 mg Zn-AA kg- 1 (equivalent to 77.49, 102.69, 127.89, 153.09, or 178.29 mg Zn kg- 1) in extruded diets (280 g kg- 1 digestible protein; isoproteic and isocaloric) for 60 days. At the end of the experimental period, after growth performance measurements, the fish were transported by car for 3 h, and blood collection was performed. The linear regression showed that the best growth performance (final weight, final biomass, weight gain, specific growth rate, and feed intake) was found in fish fed with 100 mg Zn-AA kg diet- 1 (p < 0.05). The increased dietary Zn-AA increased linearly plasma triglyceride levels, hemoglobin, mean corpuscular hemoglobin, and leukocyte values and reduced plasma total protein, cholesterol (total and LDL), and aspartate aminotransferase levels (p < 0.05). According to quadratic regression, the highest plasma glucose and alanine aminotransferase values were found in the control group (p < 0.05). In conclusion, under the conditions of this study, 100 mg Zn-AA kg diet- 1 is recommended for Nile tilapia as it can improve their growth, metabolism, physiology, and immunity.
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Cíclidos , Zinc , Animales , Zinc/metabolismo , Aminoácidos , Suplementos Dietéticos , Dieta/veterinaria , Alimentación Animal/análisisRESUMEN
Introduction: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by neuroinflammation leading to demyelination. The associated symptoms lead to a devastating decrease in quality of life. The cannabinoids and their derivatives have emerged as an encouraging alternative due to their management of symptom in MS. Objective: The aim of the study was to investigate the mechanism of action of cannabidiol (CBD), a nonpsychoactive cannabinoid, on molecular and cellular events associated with leukocyte recruitment induced by experimental autoimmune encephalomyelitis (EAE). Materials and Methods: C57BL/6 female mice were randomly assigned to the four experimental groups: C (control group), CBD (cannabidiol-treated group, 5 mg/kg i.p.; 14 days), EAE (experimental autoimmune encephalomyelitis-induced group), and EAE+CBD (experimental autoimmune encephalomyelitis-induced plus cannabidiol-treated group). Results: The results indicated that 5 mg/kg of CBD injected intraperitoneally between the 1st and 14th days of EAE could reduce the leukocyte rolling and adhesion into the spinal cord microvasculature as well cellular tissue infiltration. These results were supported by a decreased mRNA expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the spinal cord. Conclusion: Purified CBD reduces in vivo VCAM and ICAM-mediated leukocyte recruitment to the spinal cord microvasculature at EAE peak disease.