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The alarming increase in antimicrobial resistance in the last decades has prompted the search for alternatives to control infectious diseases. Antimicrobial peptides (AMPs) represent a heterogeneous class of molecules with ample antibacterial, antiviral, and antifungal effects. They can be found in many organisms, including all classes of vertebrates, providing a valuable source of new antimicrobial agents. The unique properties of AMPs make it harder for microbes develop resistance, while their immunomodulatory properties and target diversity reinforce their translational use in multiple diseases, from autoimmune disorders to different types of cancer. The latest years have witnessed a vast number of studies evaluating the use of AMPs in therapy, with many progressing to clinical trials. The present review explores the recent developments in the medicinal properties of cathelicidins, a vast family of AMPs with potent antimicrobial and immunomodulatory effects. Cathelicidins from several organisms have been tested in disease models of viral and bacterial infections, inflammatory diseases, and tumors, with encouraging results. Combining nanomaterials with active, natural antimicrobial peptides, including LL-37 and synthetic analogs like ceragenins, leads to the creation of innovative nanoagents with significant clinical promise. However, there are still important limitations, such as the toxicity of many cathelicidins to healthy host cells and low stability in vivo. The recent advances in nanomaterials and synthetic biology may help overcome the current limitations, enabling the use of cathelicidins in future therapeutics. Furthermore, a better understanding of the mechanisms of cathelicidin action in vivo and their synergy with other host molecules will contribute to the development of safer, highly effective therapies.
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Background: Autosomal recessive interleukin (IL)-12p40 deficiency is a genetic etiology of Mendelian susceptibility to mycobacterial disease (MSMD). It has been described in â¼50 patients, usually with onset at childhood with Bacille Calmette-Guérin (BCG) and Salmonella infections. Case Presentation: A male patient born to consanguineous parents was diagnosed with presumed lymph node MSMD at the age of 13 years after ocular symptoms. A positive history of inborn error of immunity was present: BCG reaction, skin abscess, and recurrent oral candidiasis. Abnormal measurements of cytokine levels, IL-12p40 and interferon-gamma (IFN-γ), lead to the diagnosis of MSMD. Genetic analysis showed a mutation in exon 7 of the IL12B gene. Currently, the patient is alive under prophylactic antibiotics. Conclusion: We report a rare case of IL-12p40 deficiency in a Latin American patient. Medical history was crucial for immune defect suspicion, as confirmed by precision diagnostic medicine tools.
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Subunidad p40 de la Interleucina-12 , Infecciones por Mycobacterium , Humanos , Masculino , Niño , Subunidad p40 de la Interleucina-12/genética , Brasil , Infecciones por Mycobacterium/diagnóstico , Infecciones por Mycobacterium/genética , Mutación , Ganglios LinfáticosRESUMEN
Introdução: A doença granulomatosa crônica (DGC) é caracterizada por um defeito na capacidade microbicida das células fagocíticas (monócitos e neutrófilos), com alta mortalidade se não diagnosticada precocemente. Os pacientes apresentam infecções recorrentes ou graves, suscetibilidade a granulomas em órgãos profundos, doenças autoimunes e doença inflamatória intestinal. Objetivo e Método: Relato de aspectos clínicos e do tratamento de cinco pacientes com doença granulomatosa crônica. Resultados: Cinco pacientes, três meninos, medianas de idade no início dos sintomas e diagnóstico de 8 meses e 48 meses, respectivamente, foram estudados por um período de 10 anos. Pneumonia (5/5) e doença micobacteriana (3/5) foram as manifestações iniciais mais comuns. Alterações pulmonares foram observadas em todos os casos. Mutações nos genes CYBB e NCF1 foram identificadas em três casos. Antibioticoprofilaxia foi instituída em todos os pacientes e três foram submetidos ao transplante de células tronco-hematopoiéticas (TCH), aos 7, 18 e 19 anos e com sobrevida atual entre 4 a 5 anos. Conclusão: O monitoramento cuidadoso de infecções graves com tratamento imediato foi crucial para a sobrevivência. O TCH, mesmo ao final da adolescência, promoveu a cura da DGC em três pacientes.
Introduction: Chronic granulomatous disease (CGD) is characterized by a defective microbicidal capacity of phagocytic cells (monocytes and neutrophils) with high mortality if not early diagnosed. Patients have recurrent or severe infections and are susceptible to granulomas in visceral organs, autoimmune diseases, and inflammatory bowel diseases. Objective and Method: To report the clinical features and treatment of 5 patients with CGD. Results: Five patients, 3 boys, with median ages at symptom onset and diagnosis of 8 months and 48 months, respectively, were followed for 10 years. Pneumonia (5/5) and mycobacterial disease (3/5) were the most common initial manifestations. Pulmonary changes were observed in all cases. Mutations in the CYBB and NCF1 genes were identified in 3 cases. All patients received antibiotic prophylaxis. Three patients underwent a hematopoietic stem cell transplant (HSCT) at 7, 18, and 19 years, with current survival of 4 to 5 years. Conclusion: Careful monitoring for severe infection with prompt treatment was crucial for survival. Even though HSCT was performed in late adolescence, it promoted the cure of CGD in 3 patients.
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HumanosRESUMEN
INTRODUCTION: Immunoglobulin represents the main therapy for patients with inborn errors of immunity (IEI) and it is a safe procedure, but adverse events (AEs) can occur with variable frequencies. OBJECTIVE: To evaluate the frequency of immediate AEs to intravenous immunoglobulin (IVIG) regular therapy in a pediatric cohort with IEI after a pre-IVIG infusion protocol. METHODS: This was a longitudinal study from 2011 to 2019 at a tertiary pediatric hospital in Brazil. RESULTS: A total of 1736 infusions were studied in 70 patients with IEI, 46 (65.7%) of whom were males and whose median age was 5.8 years old (range: 6 mo - 18 yo). Seven different brands of IVIG were used with the median loading dose of 0.57g/kg (range: 0.23 - 0.88g/Kg). According to the protocol, pre-medication and step-up infusion rate, were performed in 1305 (75.2%) infusions. Immediate AEs were noted in 10 children (14.3%) and in 22 (1.2%) infusions. Skin reactions (rash or urticaria) were the most common AE with 14 episodes (0.8% of all infusions). Almost all AEs were mild (19/86.4%), with no severe ones being observed. The majority of the AEs (81.8%) was identified at a 0.04ml/kg/min infusion rate. Gender, age at first infusion, presence of infection on the infusion day and change of the IVIG brand were evaluated and none of them were associated with AEs. CONCLUSION: The low frequency of immediate AEs in children with IEI highlights the safety and tolerability of intravenous immunoglobulin replacement with the procedures established at our center.
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Introduction Immunoglobulin represents the main therapy for patients with inborn errors of immunity (IEI) and it is a safe procedure, but adverse events (AEs) can occur with variable frequencies. Objective To evaluate the frequency of immediate AEs to intravenous immunoglobulin (IVIG) regular therapy in a pediatric cohort with IEI after a pre-IVIG infusion protocol. Methods This was a longitudinal study from 2011 to 2019 at a tertiary pediatric hospital in Brazil. Results A total of 1736 infusions were studied in 70 patients with IEI, 46 (65.7%) of whom were males and whose median age was 5.8 years old (range: 6 mo - 18 yo). Seven different brands of IVIG were used with the median loading dose of 0.57g/kg (range: 0.23 - 0.88g/Kg). According to the protocol, pre-medication and step-up infusion rate, were performed in 1305 (75.2%) infusions. Immediate AEs were noted in 10 children (14.3%) and in 22 (1.2%) infusions. Skin reactions (rash or urticaria) were the most common AE with 14 episodes (0.8% of all infusions). Almost all AEs were mild (19/86.4%), with no severe ones being observed. The majority of the AEs (81.8%) was identified at a 0.04ml/kg/min infusion rate. Gender, age at first infusion, presence of infection on the infusion day and change of the IVIG brand were evaluated and none of them were associated with AEs. Conclusion The low frequency of immediate AEs in children with IEI highlights the safety and tolerability of intravenous immunoglobulin replacement with the procedures established at our center.
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Humanos , Lactante , Preescolar , Niño , Adolescente , Enfermedades de Inmunodeficiencia Primaria , Inmunoglobulinas , Protocolos Clínicos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Errores Innatos del MetabolismoRESUMEN
Abstract Objectives: To compare the frequency of hospitalization in children with Inborn Errors of Immunity with antibody deficiency previous to intravenous immunoglobulin (pre- IVIG) with a one-year period after initial IVIG (post-IVIG). Methods: Medical reports of 45 patients during an eight-year period were reviewed from 2018 to 2019. Wilcoxon-test was used for related samples. Results: Forty-five children were included in the study, aged 29-249 months of age, and most of them (64.4%) were males. Median ages at onset symptoms and at diagnosis were 6 and 73 months old, respectively. Specific antibody deficiency and unclassified hypogammaglobulinemia were the predominant diagnoses (31.1% and 17.8%, respectively). X-linked agammaglobulinemia, Hyper IgE syndrome, Hyper IgM, transient hypogammaglobulinemia of infancy, and Common Variable Immunodeficiency (CVID) were also reported, in a low frequency. Forty-four (97.8%) patients were hospitalized before IVIG, and 10 patients (22.2%) after. Annual mean hospital admission reduced from 2.5 to 0.5, pre and post-IVIG, respectively (p < 0.0001). Mean length of stay (LOS) reduced from 71 to 4.7 days/year (p < 0.0001) in general ward and in the PICU from 17.2 days/year to zero (p < 0.0002). Pneumonia was the main cause of hospital admission with a reduction in the number of episodes per patient from an average of 2.2-0.1 per year (p < 0.001). Concomitant use of antibiotic prophylaxis did not influence the number of hospital admission. Conclusion: One-year intravenous IVIG significantly decreased the number of hospitalizations and length of stay in children with impaired antibody production. Social and economic impacts would be required.
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OBJECTIVES: To compare the frequency of hospitalization in children with Inborn Errors of Immunity with antibody deficiency previous to intravenous immunoglobulin (pre- IVIG) with a one-year period after initial IVIG (post-IVIG). METHODS: Medical reports of 45 patients during an eight-year period were reviewed from 2018 to 2019. Wilcoxon-test was used for related samples. RESULTS: Forty-five children were included in the study, aged 29-249 months of age, and most of them (64.4%) were males. Median ages at onset symptoms and at diagnosis were 6 and 73 months old, respectively. Specific antibody deficiency and unclassified hypogammaglobulinemia were the predominant diagnoses (31.1% and 17.8%, respectively). X-linked agammaglobulinemia, Hyper IgE syndrome, Hyper IgM, transient hypogammaglobulinemia of infancy, and Common Variable Immunodeficiency (CVID) were also reported, in a low frequency. Forty-four (97.8%) patients were hospitalized before IVIG, and 10 patients (22.2%) after. Annual mean hospital admission reduced from 2.5 to 0.5, pre and post-IVIG, respectively (p < 0.0001). Mean length of stay (LOS) reduced from 71 to 4.7 days/year (p < 0.0001) in general ward and in the PICU from 17.2 days/year to zero (p < 0.0002). Pneumonia was the main cause of hospital admission with a reduction in the number of episodes per patient from an average of 2.2-0.1 per year (p < 0.001). Concomitant use of antibiotic prophylaxis did not influence the number of hospital admission. CONCLUSION: One-year intravenous IVIG significantly decreased the number of hospitalizations and length of stay in children with impaired antibody production. Social and economic impacts would be required.
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Agammaglobulinemia , Inmunodeficiencia Variable Común , Agammaglobulinemia/complicaciones , Agammaglobulinemia/tratamiento farmacológico , Niño , Preescolar , Inmunodeficiencia Variable Común/complicaciones , Inmunodeficiencia Variable Común/tratamiento farmacológico , Hospitalización , Hospitales , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Lactante , MasculinoRESUMEN
Doxorubicin (DOX) is an anthracycline antibiotic used in the fight against many types of cancer. Although it is quite effective for this purpose, its clinical use is limited by its severe side effects, highlighting the relevance of efforts to identify substances that act to minimize these effects. In this work, we sought to verify the ability of andiroba oil (AO) and a nanoemulsion of andiroba oil (AN) to lessen the side effects of DOX. The animals were separated into 7 groups with 6 animals each: mice treated with AO (2000 mg/kg), AN (2000 mg/kg), the antineoplastic agent DOX (40 mg/kg), AO+DOX, AN+DOX and solvent controls was used of negative control (corn oil and nanoemulsion surfactant). AO and AN were administered for 14 consecutive days orally by gavage and on the 13th day, applied DOX by intraperitoneal route (i.p.), in order to evaluate the protective potential of andiroba. The animals were euthanized on the 15th day. Hematological, biochemical, histological, and immunohistochemical parameters were analyzed. Andiroba reduced several aspects of the severity of lesions caused by DOX, decreasing hematotoxicity and the severity of histological changes in the liver and kidneys, and reducing the frequency of apoptotic cell death. In many cases, AN showed greater efficacy than AO alone, reflecting the feasibility of using this nanotechnology to improve the pharmacokinetics of lipid compounds in the body. The study sheds new light on the therapeutic benefits of andiroba and suggests new ways for investigating how the quantity and quality of lipid compounds affect exposed organisms.
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Antineoplásicos/toxicidad , Doxorrubicina/toxicidad , Emulsiones/uso terapéutico , Meliaceae , Aceites de Plantas/uso terapéutico , Animales , Emulsiones/aislamiento & purificación , Emulsiones/farmacología , Femenino , Inyecciones Intraperitoneales , Riñón/efectos de los fármacos , Riñón/patología , Hígado/efectos de los fármacos , Hígado/patología , Ratones , Aceites de Plantas/aislamiento & purificación , Aceites de Plantas/farmacología , Bazo/efectos de los fármacos , Bazo/patologíaRESUMEN
Introdução: Os jovens estão entre os grupos mais vulneráveis na 4ª década da epidemia de HIV/Aids. Dentre as estratégias de prevenção voltadas a esta população, a camisinha tem sido uma das mais relevantes. As intervenções escolares para a educação em sexualidade são um importante meio de promoção do seu uso. E a escola se trata do espaço mais adequado para isso. No esforço de contribuir para tais ações, importante investimento científico tem sido construído ao longo de quase quarenta anos. Descrever esse campo com abrangência global e na perspectiva da agência da juventude permite uma análise para o futuro das respostas à epidemia na garantia de direitos sexuais e reprodutivos. Objetivo: Caracterizar a produção acadêmica na proposição de intervenções escolares de incentivo ao uso de preservativo para a prevenção ao HIV/Aids na 4ª década da epidemia. Métodos: Foi realizada busca sistemática e rigorosa em 13 bases de dados para identificação de estudos relevantes sobre intervenções escolares que incentivaram o uso de camisinha para prevenção de jovens ao HIV/Aids a partir de 2011. Pares independentes executaram seleção e extração dos estudos primários. Foram selecionados 22 artigos. As intervenções foram tomadas por unidade de análise, descritas e então caracterizadas a partir da agência dos participantes, de acordo com o referencial das intervenções formativas do Laboratório de Mudança. Resultados: Foram identificadas 17 intervenções, da América do Norte, Europa e África, elaboradas a partir de estudos quasi-experimentais e ensaios randomizados controlados. Ainda prevalece a lógica do risco em detrimento de intervenções abrangentes. A estrutura das intervenções limita a agência dos jovens participantes. Conclusão: As intervenções escolares que incentivam o uso de camisinha na 4ª década da epidemia de HIV/Aids têm se afastado de uma resposta mais emancipatória.
Introduction: Youngsters are one of the more vulnerable groups to HIV/Aids in the epidemic 4th decade. Condom has been amongst important prevention strategies to them. School-based interventions for sexuality education are appropriated actions to promote condom use. Great scientific contribution has been made in almost forty years. Describing that specific field in global extent and through the lens of youth agency facilitates analysing future responses to the epidemic, considering sexual and reproductive rights. Objective: Summarizing the scholar production proposing school-based interventions that promote condom use in the 4th decade of HIV/Aids epidemic. Methods: A scoping review in which systematic search was carried out in 13 databases to identify relevant studies on the school-based interventions that promote condom use in the 4th decade of HIV/Aids epidemic since 2011. Independent peers did the selection and extraction of the studies. Then 22 papers were selected to compose the review. Interventions were taken by analysis unit, described and characterized with Change Laboratory formative intervention as theoretical framework. Results: 17 interventions were identified, representing North America, Europe and Africa. The study designs used were randomized controlled trials and quasi-experimental only. Risk reduction paradigm of prevention is still stronger than comprehensive one. Interventions structure restricts youth agency. Conclusion: School-based interventions that promote condom use in the 4th decade of HIV/Aids epidemic are still far from an emancipatory response.
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Humanos , Adolescente , Educación Sexual , VIH , Condones , Prevención de Enfermedades , EpidemiasRESUMEN
Malachite green (MG) is a triphenylmethane dye that is widely used in aquaculture as a fungicide, bactericide, ectoparasiticide, and antiprotozoal. There is great debate regarding the potential for this compound to trigger adverse effects. Here, we review the previous findings and then evaluate the lethal and sublethal effects of MG in the species Hemichromis bimaculatus (jewelfish). The lethal concentration for 50% of the fish in 96 h was 1 mg/L. We observed a dose-dependent increase in the percentage of fish mortality as well as physical and behavioral changes. We further found that the highest tested sublethal dose significantly increased the DNA damage index identified using the comet assay (74.97 ± 13.8 at a significant level of P < 0.05 for the 0.75 mg/L concentration), but did not significantly alter the results of the micronucleus test. Although our results suggest that MG confers risks on exposed fish, the findings were significant only at the highest exposure concentration (0.75 mg/L). At lower concentrations (0.25 mg/L and 0.5 mg/L), no adverse effect was observed. The maximum MG concentration recommended for use in ornamental fish farming is 0.2 mg/L. Therefore, our results suggest that, specifically for the parameters analyzed in this work, MG does not have any adverse effect when users strictly adhere to the recommended concentration criteria for ornamental fish.
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Branquias , Contaminantes Químicos del Agua , Animales , Ensayo Cometa , Daño del ADN , Pruebas de Micronúcleos , Colorantes de RosanilinaRESUMEN
Andiroba (Carapa guianensis Aubl) is an Amazonian plant whose oil has been widely used in traditional medicine for various purposes, including anti-inflammation. Research reports indicate that the oil can confer antitumor activity due to the presence of fatty acids, which can directly influence cell death mechanisms. Thus, andiroba oil (AO) has gained interest for its potential to be used in antineoplastic therapies. Here, we report an in vitro analysis of the cytotoxic and mutagenic potential of AO in the gastric cancer cell line, ACP02. Cell survival was assessed by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, differential staining with ethidium bromide and acridine orange assessed apoptosis-necrosis, and mutagenesis was assessed by the micronucleus test. The apolar oil was first diluted in 0.1% dimethyl sulfoxide (DMSO) and then further diluted to six concentrations (0.01, 0.1, 1, 10 and 100 µg/mL and 1 mg/mL) in RPMI medium. Controls included RPMI alone (negative control) and 0.1% DMSO diluted in medium (vehicle control). The MTT test showed that AO significantly reduced cell viability (P < .05) only when the highest tested concentration was applied for 48 hours. The apoptosis/necrosis test showed that the highest concentration of AO induced cell death by apoptosis at 24 and 48 hours. There was no statistically significant increase in the frequency of micronuclei. The ability of the AO to decrease the viability of ACP02 cells via apoptosis, without exerting mutagenic effects, suggests that the oil could be useful as an alternative therapeutic agent for primary tumors of stomach cancer.
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Apoptosis/efectos de los fármacos , Citotoxicidad Inmunológica/efectos de los fármacos , Citotoxinas/toxicidad , Meliaceae/toxicidad , Mutagénesis/efectos de los fármacos , Mutágenos/toxicidad , Aceites de Plantas/toxicidad , Neoplasias Gástricas/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Brasil , Células Cultivadas/efectos de los fármacos , Humanos , Meliaceae/química , Aceites de Plantas/química , Plantas Medicinales/química , Plantas Medicinales/toxicidadRESUMEN
Libidibia ferrea (juca) is a plant belonging to the Fabaceae (Leguminosae) family, whose antioxidant activity has been widely described in the literature. We evaluated this parameter of Aqueous ethanol extract (AE), ethyl acetate (ACO), chloroform (CLO) and hexane (HEX) extracts of L. ferrea. We then tested the most active extract for its toxicity and ability to inhibit migratory activity in the ACP02 gastric adenocarcinoma cell line in vitro. The AE and ACO extracts both had antioxidant activity, the AE extract showing greater potential. This may reflect that both extracts contained phenolic compounds. Although AE extract showed no cytotoxic, mutagenic or genotoxic effect, it altered cell morphology and migration activity. Analysis of apoptosis/necrosis indicated that this parameter does not appear to account for the apparent ability of AE to inhibit cancer cell migration. We speculate that the morphological changes in AE-treated cells could be due to cytoskeleton alterations related to the presence of myo-inositol in AE extract. Together, our results demonstrate this extract of L. ferrea can act as an exogenous antioxidant and might prove useful in efforts to fight secondary tumors.
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Antineoplásicos/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Caesalpinia/química , Movimiento Celular/efectos de los fármacos , Extractos Vegetales/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/farmacología , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Etanol , Humanos , Solventes/química , Neoplasias Gástricas/patologíaRESUMEN
Previous studies have reported the anti-obesity effects of α, ß-Amyrin in high fat-fed mice. This study aimed to evaluate whether α, ß-Amyrin has an anti-adipogenic effect in 3T3-L1 murine adipocytes and to explore the possible underlying mechanisms. 3T3-L1 pre-adipocytes were differentiated in a medium containing insulin, dexamethasone, and 1-methyl-3-isobutylxanthine. Cytotoxicity of α, ß-Amyrin was assessed by MTT assay. Lipid content in adipocytes was determined by Oil-Red O staining. In addition, the protein expression levels of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding proteins alpha (C/EBPα), beta (C/EBPß), and delta (C/EBPδ) and glucose transporter 4 (GLUT4) were determined by qRT-PCR and western blot analysis. Oil-Red O staining revealed markedly reduced fat accumulation by α, ß-Amyrin (6.25-50 µg/mL) without affecting cell viability. Furthermore, our results indicate that α, ß-Amyrin can significantly suppress the adipocyte differentiation by downregulating the expression levels of adipogenesis-related key transcription factors such as PPARγ and C/EBPα, but not C/EBPß or C/EPBδ. In addition, the protein expression of membrane GLUT4 in 3T3- L1 adipocytes treated with α, ß-Amyrin was significantly higher than in control cells, indicating that α, ß-Amyrin augments glucose uptake. These findings suggest that α, ß-Amyrin exerts an anti-adipogenic effect principally via modulation of lipid and carbohydrate metabolism in 3T3-L1cells. The present in vitro findings, taken together with our earlier observation of the anti-obesity effect in vivo, suggest that α, ß-Amyrin can be developed as a new therapeutic agent for treatment and prevention of obesity.
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Adipocitos/efectos de los fármacos , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Diferenciación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Ácido Oleanólico/análogos & derivados , PPAR gamma/metabolismo , Triterpenos Pentacíclicos/farmacología , Células 3T3-L1 , Adipogénesis/efectos de los fármacos , Animales , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Proteínas de Unión a Ácidos Grasos/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo , Ratones , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Ácido Oleanólico/farmacología , Extractos Vegetales/farmacologíaRESUMEN
ABSTRACT CONTEXT: Complex karyotypes in acute myeloid leukemia (AML) are characterized by an overall low response rate with frequent relapses after clinical treatment. CASE REPORT: Here, we describe the case of a 61-year-old obese female with clinically diagnosed AML who presented a complex karyotype involving an uncommon abnormality: ring chromosome 11. Immunophenotypic analysis confirmed the diagnosis. Classical and molecular cytogenetic analyses, using GTG banding and FISH (fluorescence in situ hybridization), revealed the presence of complex structural rearrangement involving r(11), add(12)(p13), der(5) and der(13). CONCLUSIONS: Molecular cytogenetic analysis is suitable for better identification and characterization of chromosomal rearrangements in AML. Case reports like this, as well as population-based studies, are necessary for understanding the karyotypic changes that occur in humans.
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Humanos , Femenino , Persona de Mediana Edad , Cromosomas en Anillo , Leucemia Mieloide Aguda/genética , Translocación Genética , Hibridación Fluorescente in Situ , Análisis Citogenético , CariotipoRESUMEN
CONTEXT: Complex karyotypes in acute myeloid leukemia (AML) are characterized by an overall low response rate with frequent relapses after clinical treatment. CASE REPORT: Here, we describe the case of a 61-year-old obese female with clinically diagnosed AML who presented a complex karyotype involving an uncommon abnormality: ring chromosome 11. Immunophenotypic analysis confirmed the diagnosis. Classical and molecular cytogenetic analyses, using GTG banding and FISH (fluorescence in situ hybridization), revealed the presence of complex structural rearrangement involving r(11), add(12)(p13), der(5) and der(13). CONCLUSIONS: Molecular cytogenetic analysis is suitable for better identification and characterization of chromosomal rearrangements in AML. Case reports like this, as well as population-based studies, are necessary for understanding the karyotypic changes that occur in humans.
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Leucemia Mieloide Aguda/genética , Cromosomas en Anillo , Análisis Citogenético , Femenino , Humanos , Hibridación Fluorescente in Situ , Cariotipo , Persona de Mediana Edad , Translocación GenéticaRESUMEN
This study investigated phenotypic and functional characteristics of lymphocytes in children with common variable immunodeficiency (CVID) and unclassified hypogammaglobulinemia (UH), as well as B-cell subsets in non-consanguineous parents. Blood samples of 30 children, CVID (n = 9), UH (n = 9), healthy donors HD (n = 12), and 19 adults (parents and controls) were labeled by a combination of surface markers to identify CD4, CD8 T-cell and B-cell subpopulations. T-cell cytokine production in children was analyzed in vitro after stimulation with phytohemagglutinin (PHA) and tetanus toxoid. We observed low percentages of switched memory B cells in children with CVID, increase in total CD4+ T-cell counts, and high percentages of transitional B cells only in UH group. Analysis of T-cell immunity showed that CVID children had decreased percentages of CD8+ IFN-γ-producing cells after stimulation with PHA and tetanus toxoid. Parent of children with CVID had low percentages of naive B cell and increased percentages of memory B cells in comparison with controls. These results suggest that (i) early combined immune defect in children with CVID and (ii) a possible familial B-cell disturbance in pediatric CVID.
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Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Inmunodeficiencia Variable Común/patología , Adolescente , Adulto , Niño , Preescolar , Citocinas/metabolismo , Femenino , Humanos , Factores Inmunológicos , Masculino , Persona de Mediana Edad , Fitohemaglutininas/inmunología , Toxoide Tetánico/inmunologíaRESUMEN
This study investigated whether circulating α4ß7+ expressing T cells could serve as a potential marker for gastrointestinal (GI) disease activity in patients with CVID. The analysis of α4ß7+ T cells in the peripheral blood of 36 patients and 22 healthy donors (HD) revealed increased percentages of α4ß7+ conventional memory CD4 T cells and Tregs, but not among CD8 T-cell populations in patients with CVID compared to HD. No differences between patients with and without chronic or acute GI symptoms were observed. EUROClass smB- and 21lo patients, had higher percentages of α4ß7+ memory CD4 T cells compared to HD and smB+ or 21norm patients, respectively. In summary, the detection of α4ß7+ T cells in the peripheral blood did not correlate with active or chronic gastrointestinal disease. The increase of these cells in smB- and 21lo patients adds another piece to the immune dysregulation observed in these patients.
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Linfocitos T CD4-Positivos/inmunología , Inmunodeficiencia Variable Común/inmunología , Enfermedades Gastrointestinales/inmunología , Integrinas/inmunología , Adulto , Anciano , Linfocitos T CD8-positivos/inmunología , Femenino , Enfermedades Gastrointestinales/diagnóstico , Humanos , Memoria Inmunológica , Masculino , Persona de Mediana EdadRESUMEN
Obesity remains a global problem. In search of phytochemicals that have antiobesity potential, this study evaluated α,ß-amyrin, a triterpenoid mixture from Protium heptaphyllum, on high-fat diet-induced obesity in mice. Groups of mice (n = 8) were fed a normal diet or a high-fat diet, and were orally treated or not treated with either α,ß-amyrin (10 or 20 mg/kg) or sibutramine (10 mg/kg) for 15 weeks. Variables measured at termination were body weight, visceral fat accumulation, adipocyte surface area, peroxisome proliferator-activated receptor gamma, and lipoprotein lipase expressions in adipose tissue, the levels of plasma glucose and insulin, the satiety hormones ghrelin and leptin, the digestive enzymes amylase and lipase, and the inflammatory mediators TNF-α, interleukin-6, and MCP-1. Results showed that α,ß-amyrin treatment resulted in lower high-fat diet-induced increases in body weight, visceral fat content, adipocyte surface area, peroxisome proliferator-activated receptor gamma, and lipoprotein lipase expressions, and blood glucose and insulin levels. Additionally, the markedly elevated leptin and decreased ghrelin levels seen in the high-fat diet-fed control mice were significantly modulated by α,ß-amyrin treatment. Furthermore, α,ß-amyrin decreased serum TNF-α and MCP-1. These results suggest that α,ß-amyrin could be beneficial in reducing high-fat diet-induced obesity and associated disorders via modulation of enzymatic, hormonal, and inflammatory responses.
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Fármacos Antiobesidad/farmacología , Obesidad/tratamiento farmacológico , Ácido Oleanólico/análogos & derivados , Grasa Abdominal/efectos de los fármacos , Adipocitos/citología , Adipocitos/efectos de los fármacos , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Burseraceae/química , Ciclobutanos/farmacología , Dieta Alta en Grasa , Ghrelina/sangre , Insulina/sangre , Leptina/sangre , Lípidos/sangre , Lipoproteína Lipasa/metabolismo , Masculino , Ratones , Obesidad/sangre , Obesidad/etiología , Ácido Oleanólico/química , Ácido Oleanólico/aislamiento & purificación , Ácido Oleanólico/farmacología , PPAR gamma/metabolismo , Fitoterapia , Resistina/sangreRESUMEN
PURPOSE: Health-related quality of life (HRQOL) has not been examined in patients with predominant antibody deficiency both pre- and post-immunoglobulin G (IgG) treatment initiation. HRQOL and health resource utilization (HRU) were assessed in newly diagnosed patients with primary immunodeficiency disease (PIDD) pre- and 12 months post-IgG treatment initiation. METHODS: Adults (age ≥18 years) completed the 36-item Short Form Health Survey, version 2; pediatric patients (PP)/caregivers completed the Pediatric Quality of Life Inventory (PedsQL). Scores were compared with normative data from the US general population (GP) and patients with other chronic conditions (OCC). RESULTS: Seventeen adult patients (APs), 8 PPs, and 8 caregivers completed baseline assessments. APs had significantly lower baseline mean physical component summary scores versus GP (37.4 vs 50.5, p < 0.01) adults with chronic back pain (44.1, p < 0.05) or cancer (44.4, p < 0.05) and lower mental component summary scores versus GP (41.6 vs 49.2, p < 0.05). PPs had lower PedsQL total (63.1 vs 82.7), physical summary (64.5 vs 84.5), and psychosocial summary (62.5 vs 81.7) scores versus GP. Post-IgG treatment, 14 APs, 6 PPs, and 8 caregivers completed assessments. Hospital admissions (0.2 versus 1.8, p < 0.01), serious infections (3.3 versus 10.9, p < 0.01) and antibiotic prescriptions (3.0 versus 7.1; p < 0.01) decreased significantly overall. While APs reported significant improvement in role-physical (p = 0.01), general health (p < 0.01), and social functioning (p = 0.02) and caregivers in vitality (p < 0.01), PPs did not. CONCLUSIONS: Pre-IgG treatment, patients with PIDD experienced diminished HRQOL versus GP and patients with OCC; post-treatment, HRU decreased and certain HRQOL aspects improved for APs and caregivers.