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Medicinas Complementárias
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2.
Front Immunol ; 14: 1298416, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38259457

RESUMEN

Context: Ma Xing Shi Gan Decoction (MXSGD) is a traditional remedy for treating lung injuries that was developed by the Typhoid and Fever School of Pharmaceutical Biology. It has antitussive and expectorant effects, anti-inflammatory, antiviral, regulates the body's immunity, etc. Aim: The aim of this study is to investigate whether MXSGD can ameliorate cyclosporine A (CsA)-induced hypoimmunity lung injury by regulating microflora metabolism. Methods: Establishment of a model for CsA-induced hypoimmunity lung injury. Using 16S rRNA high-throughput sequencing and LC-MS, the effects of MXSGD on gut flora and lung tissue microecology of mice with CsA-induced hypoimmunity were investigated. Results: MXSGD was able to preserve lung tissue morphology and structure, reduce serum inflammatory marker expression and protect against CsA-induced lung tissue damage. Compared to the model, MXSGD increased beneficial gut bacteria: Eubacterium ventriosum group and Eubacterium nodatum group; decreased intestinal pathogens: Rikenellaceae RC9 intestinal group; reduced the abundance of Chryseobacterium and Acinetobacter, promoted the production of Lactobacillus and Streptococcus, and then promoted the lung flora to produce short-chain fatty acids. MXSGD was able to enhance the expression of serum metabolites such as Americine, 2-hydroxyhexadecanoylcarnitine, Emetine, All-trans-decaprenyl diphosphate, Biliverdin-IX-alpha, Hordatin A and N-demethyl mifepristone in the CsA-induced hypoimmunity lung injury model. Conclusion: MXSGD can restore gut and lung microbiota diversity and serum metabolite changes to inhibit inflammation, ameliorate CsA-induced hypoimmunity lung injury.


Asunto(s)
Acinetobacter , Medicamentos Herbarios Chinos , Síndromes de Inmunodeficiencia , Lesión Pulmonar , Animales , Ratones , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/tratamiento farmacológico , Ciclosporina , ARN Ribosómico 16S/genética
3.
J Immunol Methods ; 511: 113385, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36372267

RESUMEN

The advantage of the newer biological therapies is that the immunosuppressive effect is targeted, in contrast, to the standard, traditional immunomodulatory agents, which have a more global effect. However, there are unintended targets and consequences, even to these "precise" therapeutics, leading to acquired or secondary immunodeficiencies. Besides depleting specific cellular immune subsets, these biological agents, which include monoclonal antibodies against biologically relevant molecules, often have broader functional immune consequences, which become apparent over time. This review focuses on acquired B-cell immunodeficiency, secondary to the use of B-cell depleting therapeutic agents. Among the many adverse consequences of B-cell depletion is the risk of hypogammaglobulinemia, failure of B-cell recovery, impaired B-cell differentiation, and risk of infections. Factors, which modulate the outcomes of B-cell depleting therapies, include the intrinsic nature of the underlying disease, the concomitant use of other immunomodulatory agents, and the clinical status of the patient and other co-existing morbidities. This article seeks to explore the mechanism of action of B-cell depleting agents, the clinical utility and adverse effects of these therapies, and the relevance of systematic and serial laboratory immune monitoring in identifying patients at risk for developing immunological complications, and who may benefit from early intervention to mitigate the secondary consequences. Though these biological drugs are gaining widespread use, a harmonized approach to immune evaluation pre-and post-treatment has not yet gained traction across multiple clinical specialties, because of which, the true prevalence of these adverse events cannot be determined in the treated population, and a systematic and evidence-based dosing schedule cannot be developed. The aim of this review is to bring these issues into focus, and initiate a multi-specialty, data-driven approach to immune monitoring.


Asunto(s)
Linfocitos B , Terapia Biológica , Síndromes de Inmunodeficiencia , Agentes Inmunomoduladores , Humanos , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Linfocitos B/efectos de los fármacos
4.
Hum Genet ; 141(7): 1279-1286, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35182234

RESUMEN

Mutations in the X-linked gene MAGT1 cause a Congenital Disorder of Glycosylation (CDG), with two distinct clinical phenotypes: a primary immunodeficiency (XMEN disorder) versus intellectual and developmental disability. It was previously established that MAGT1 deficiency abolishes steady-state expression of the immune response protein NKG2D (encoded by KLRK1) in lymphocytes. Here, we show that the reduced steady-state levels of NKG2D are caused by hypoglycosylation of the protein and we pinpoint the exact site that is underglycosylated in MAGT1-deficient patients. Furthermore, we challenge the possibility that supplementation with magnesium restores NKG2D levels and show that the addition of this ion does not significantly improve NKG2D steady-state expression nor does it rescue the hypoglycosylation defect in CRISPR-engineered human cell lines. Moreover, magnesium supplementation of an XMEN patient did not result in restoration of NKG2D expression on the cell surface of lymphocytes. In summary, we demonstrate that in MAGT1-deficient patients, the lack of NKG2D is caused by hypoglycosylation, further elucidating the pathophysiology of XMEN/MAGT1-CDG.


Asunto(s)
Proteínas de Transporte de Catión , Síndromes de Inmunodeficiencia , Trastornos Linfoproliferativos , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Humanos , Magnesio/metabolismo , Subfamilia K de Receptores Similares a Lectina de Células NK/genética , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X/genética
5.
Am J Chin Med ; 49(1): 95-111, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33416022

RESUMEN

Methamphetamine (METH) is an extremely addictive drug that has raised serious public health concerns recently. METH addiction not only results in neuronal cytotoxicity, but it also affects immune cell activity, including T lymphocytes. 6,4,7[Formula: see text]-trihydroxyflavanone (THF), isolated from Dalbergia odorifera, has been studied for its antibacterial activity, but evidence for whether THF has an anti-cytotoxic and protective effect on T cell activation exposed to METH is lacking. In this study, results showed that treatment with THF was not cytotoxic to Jurkat T cells but dose-dependently mitigated the cytotoxicity induced by exposure to METH. The Western blot results demonstrating pre-treatment with THF maintained the expression of anti-apoptotic proteins and phosphorylation of PI3K/Akt/mTOR downregulated by treatment with METH. Furthermore, we found that decreased expression of IL-2 and CD69 by METH exposure was partially restored, and viability was significantly prevented by pre-treatment with THF in activated T cells. These findings were involved in re-elevated expression of anti-apoptotic proteins as well as recovered pathways including MAPK/PI3K/Akt/mTOR in activated T cells pre-exposed to METH. Our results suggest beneficial effects of THF against the cytotoxic and immune-modulating effect of METH on T cells and therapeutic potential of THF for patients with immunodeficiency caused by METH addiction.


Asunto(s)
Apoptosis/efectos de los fármacos , Isoflavonas/farmacología , Activación de Linfocitos/efectos de los fármacos , Metanfetamina/efectos adversos , Linfocitos T/inmunología , Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Células Cultivadas , Dalbergia/química , Humanos , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Síndromes de Inmunodeficiencia/etiología , Isoflavonas/aislamiento & purificación , Isoflavonas/uso terapéutico , Células Jurkat , Metanfetamina/toxicidad , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación/efectos de los fármacos , Fitoterapia , Trastornos Relacionados con Sustancias/complicaciones , Linfocitos T/patología , Serina-Treonina Quinasas TOR/metabolismo
6.
Ear Nose Throat J ; 100(3): NP161-NP163, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31550931

RESUMEN

Deep neck infection (DNI) refers to infections in spaces created by superficial and deep cervical fascia around the muscles and organs in the neck. Vitamin D is highly important for an effective immune system. Vitamin D receptors (VDR) have been identified in immune system cells, and particularly in T and B lymphocytes, macrophages, and dendritic cells. Vitamin D deficiency is thought to result in impaired immune response, decreased leukocyte chemotaxis, and an increased disposition to infection. The purpose of this study was to investigate whether vitamin D deficiency is an underlying occult factor in the development of DNI. Sixty-five patients aged 6 to 90, diagnosed with DNI, and 70 healthy age- and sex-compatible cases were included in the study. Serum levels of calcium, phosphorus, parathyroid hormone, and 25-hydroxy vitamin D (25(OH)D) were determined in each case. 25-hydroxy vitamin D levels above 20 ng/mL were regarded as normal, 12 to 20 ng/mL as insufficient, 5 to 12 ng/mL as deficient, and less than 5 ng/mL as severely deficient. Mean serum 25(OH)D levels were 10.4 (6.2) ng/mL in the patient group and 15.5 (6.4) ng/mL in the control group (P < .01). This difference was statistically significant (P < .01). Vitamin D was within normal limits in 9.2% (n = 6) of cases in the study group, insufficient in 29.2% (n = 19), deficient in 35.3% (n = 23), and severely deficient in 26.2% (n = 17). The equivalent values in the control group were 21.4% (n = 15), 48.5% (n = 34), 30% (n = 21), and 0% (n = 0). Serum 25(OH)D levels were significantly lower in patients with DNI compared to the healthy cases; 25(OH)D levels may be a factor in the development of DNI.


Asunto(s)
Síndromes de Inmunodeficiencia/sangre , Cuello/microbiología , Infecciones de los Tejidos Blandos/inmunología , Deficiencia de Vitamina D/inmunología , Vitamina D/análogos & derivados , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Calcio/sangre , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Fósforo/sangre , Factores de Riesgo , Método Simple Ciego , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Adulto Joven
7.
Expert Rev Clin Immunol ; 16(9): 911-921, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32783541

RESUMEN

INTRODUCTION: Secondary immunodeficiency diseases (SID) caused by hematological malignancies (HMs), stem cell transplant (SCT), and associated therapies are mainly characterized by the presence of hypogammaglobulinemia or antibody production deficits. AREAS COVERED: The authors summarized the scientific literature on disease burden of SIDs in patients who had HMs or SCT. Systematic searches were conducted to identify English-language articles from 1994-2020, reporting on clinical, humanistic, and economic burdens of SID due to HMs or SCT. Definitions of SID and serum immunoglobulin G thresholds varied across 24 eligible studies. In most (n = 16) studies, patients received immunoglobulin replacement therapy (IGRT). Several studies found IGRT was associated with significant reductions in rates of infection and antimicrobial use. However, 1 study found no statistically significant difference in antibiotic use with IGRT. Only 3 studies reported on quality of life, and no economic studies were identified. EXPERT OPINION: Overall, the findings show several beneficial effects of IGRT on clinical outcomes and quality of life; however, disparate definitions, infrequent reporting of statistical significance, and scarcity of clinical trial data after the 1990s present areas for further investigation. This paucity indicates an unmet need of current evidence to assess the benefits of IGRT in SID.


Asunto(s)
Terapia Biológica/métodos , Neoplasias Hematológicas/terapia , Inmunoglobulinas/uso terapéutico , Síndromes de Inmunodeficiencia/terapia , Trasplante de Células Madre , Neoplasias Hematológicas/complicaciones , Humanos , Síndromes de Inmunodeficiencia/etiología , Resultado del Tratamiento
8.
Nutrients ; 12(5)2020 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-32357579

RESUMEN

BACKGROUND: Vitamin D3 supplements are available as tablets or oil drops, but there is no consensus as to whether either of these preparations is more effective than the other. METHODS: We compared the effectiveness of tablets versus oil in raising S-25-hydroxyvitamin D (S-25-OHD) in plasma by re-analyzing data from a previously performed observational study in which immunodeficient patients with S-25-OHD concentrations <75 nmol/L were randomly prescribed vitamin D3 tablets (1600 IU/day) or vitamin D3 oil-drops (1500 IU/day) for twelve months. Tablets and oil were compared for the effect on S-25-OHD concentrations after 3-5 months and antibiotic use. RESULTS: Data on S-25-OHD after ≥ 3 months was available for 137 patients treated with tablets and 69 with oil drops. Both groups exhibited a significant increase in S-25-OHD-oil-drops from 55 to 86 nmol/L and tablets from 52 to 87 nmol/L-with no difference between groups (p = 0.77). In a subgroup of patients without immunoglobulin replacement, vitamin D3 supplementation with oil drops (n = 34) but not with tablets (n = 60) resulted in significantly lower antibiotic administration (p < 0.001 and p = 0.58). CONCLUSION: Vitamin D3 supplementation with tablets and oil drops were equally efficient in raising S-25-OHD concentrations. Only oil drops caused a reduction in antibiotic consumption in immuno-deficient patients who did not receive immunoglobulin replacement.


Asunto(s)
Colecalciferol/administración & dosificación , Suplementos Dietéticos , Síndromes de Inmunodeficiencia/sangre , Vitamina D/análogos & derivados , Antibacterianos/administración & dosificación , Análisis de Datos , Conjuntos de Datos como Asunto , Formas de Dosificación , Utilización de Medicamentos , Femenino , Humanos , Masculino , Fenómenos Fisiológicos de la Nutrición , Aceites , Comprimidos , Factores de Tiempo , Vitamina D/sangre
9.
Arq. Asma, Alerg. Imunol ; 3(3): 207-258, jul.set.2019. ilus
Artículo en Portugués | LILACS | ID: biblio-1381240

RESUMEN

O presente guia apresenta revisão extensa sobre imunobiológicos utilizados, liberados e ainda sob estudo, para o tratamento da asma, doenças alérgicas e imunodeficiências. Além das características físico-químicas de alguns desses fármacos, são revisadas as indicações e os resultados de estudos clínicos realizados para avaliar eficácia e segurança. Separados por doença específica, são apresentados os principais agentes disponíveis e aprovados para utilização segundo as normas regulatórias nacionais.


This guide presents an extensive review of immunobiological drugs used, approved and/or under investigation for the treatment of asthma, allergic diseases and immunodeficiencies. In addition to the physicochemical characteristics of some of these drugs, their indications and results of clinical studies evaluating efficacy and safety are reviewed. The main agents available and approved for use in each specific disease according to national regulatory standards are presented.


Asunto(s)
Humanos , Asma , Sinusitis , Terapia Biológica , Proteínas Recombinantes de Fusión , Dermatitis Atópica , Angioedemas Hereditarios , Omalizumab , Hipersensibilidad a los Alimentos , Urticaria Crónica , Anafilaxia , Anticuerpos Monoclonales , Seguridad , Terapéutica , Productos Biológicos , Preparaciones Farmacéuticas , Enfermedad , Eficacia , Citocinas , Regulación Gubernamental , Alergia e Inmunología , Síndromes de Inmunodeficiencia , Inmunoterapia
10.
J Ethnopharmacol ; 245: 112047, 2019 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-31394179

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Description of the pharmacological activities of Sanghuang mushrooms (Inonotus Sanghuang) can be traced back to Tang dynasty of China 1300 years ago. This mushroom has been widely accepted in China, Japan, Korea and certain regions of Europe as a nutraceutical medicine for enhancing immunity or an alternative medicine for prevention or inhibition of tumorigenesis. However, this mushroom is rarely available from the mulberry trees in the wild because of the rigorous conditions needed for formation of the Sanghuang mushrooms. AIM OF THE STUDY: This study aims to establish a practical protocol for culture, particularly for a bunch of production of Sanghuang mushrooms possibly to commercialize the cultured Sanghuang based on deep comparison of quality and pharmacological activities between the cultured and the wild Sanghuang. MATERIALS AND METHODS: A phylogenetic tree containing five strains of the wild Sanghuang was constructed using rDNA markers. Different temperatures and medium compositions were surveyed to develop a practical protocol for culture of the Sanghuang mushrooms. 5-fluorouracil was used to induce the immunodeficient mice. Chemotherapeutic components and pharmacological activities were deeply analyzed between a cultured strain (SG) and three strains of the wild Sanghuang. RESULTS: Maintenance of a temperature of 22-28 °C and a high relative humidity of 90-95%, and use of a high ratio (80%) of mulberry tree sticks in the medium were critical to successful culture of Sanghuang. The cultured mushrooms were yellow with a uniform shape, while the wild Sanghuang was dark brown with a smaller and irregular shape. The cultured mushrooms contained significantly higher levels of polysaccharides, amino acids, and water-soluble nutraceuticals, whereas flavones in the wild Sanghuang were significantly higher (P < 0.05). Use of a dose of 8 mg/kg or 16 mg/kg to immunoregenerate the immunodeficient mice was comparable between the cultured and wild Sanghang based on analysis of hematological parameters and histological examination of the thymus and spleen in the treated mice. CONCLUSIONS: This study highlights the potential of the immunoregenerative functions of the cultured Sanghuang for cancer chemotherapy and suggests that the cultured Sanghuang can be an alternative to wild Sanghuang used for nutraceutical medicine.


Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Agaricales , Síndromes de Inmunodeficiencia/terapia , Agaricales/genética , Animales , Antineoplásicos , Biónica , Recuento de Células Sanguíneas , Femenino , Fluorouracilo , Síndromes de Inmunodeficiencia/inducido químicamente , Ratones Endogámicos BALB C , Filogenia , Bazo/efectos de los fármacos , Bazo/patología , Timo/efectos de los fármacos , Timo/patología
11.
BMC Infect Dis ; 19(1): 522, 2019 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-31200658

RESUMEN

BACKGROUND: To describe patients with inherited and acquired complement deficiency who developed invasive meningococcal disease (IMD) in England over the last decade. METHODS: Public Health England conducts enhanced surveillance of IMD in England. We retrospectively identified patients with complement deficiency who developed IMD in England during 2008-2017 and retrieved information on their clinical presentation, vaccination status, medication history, recurrence of infection and outcomes, as well as characteristics of the infecting meningococcal strain. RESULTS: A total of 16 patients with 20 IMD episodes were identified, including four with two episodes. Six patients had inherited complement deficiencies, two had immune-mediated conditions associated with complement deficiency (glomerulonephritis and vasculitis), and eight others were on Eculizumab therapy, five for paroxysmal nocturnal haemoglobinuria and three for atypical haemolytic uraemic syndrome. Cultures were available for 7 of 11 episodes among those with inherited complement deficiencies/immune-mediated conditions and the predominant capsular group was Y (7/11), followed by B (3/11) and non-groupable (1/11) strains. Among patients receiving Eculizumab therapy, 3 of the 9 episodes were due to group B (3/9), three others were NG but genotypically group B, and one case each of groups E, W and Y. CONCLUSIONS: In England, complement deficiency is rare among IMD cases and includes inherited disorders of the late complement pathway, immune-mediated disorders associated with low complement levels and patients on Eculizumab therapy. IMD due to capsular group Y predominates in patient with inherited complement deficiency, whilst those on Eculizumab therapy develop IMD due to more diverse capsular groups including non-encapsulated strains.


Asunto(s)
Proteínas del Sistema Complemento/deficiencia , Síndromes de Inmunodeficiencia/complicaciones , Infecciones Meningocócicas/complicaciones , Infecciones Meningocócicas/microbiología , Neisseria meningitidis/genética , Adolescente , Adulto , Anticuerpos Monoclonales Humanizados/efectos adversos , Niño , Preescolar , Inglaterra/epidemiología , Genotipo , Humanos , Síndromes de Inmunodeficiencia/etiología , Infecciones Meningocócicas/epidemiología , Programas Nacionales de Salud/estadística & datos numéricos , Polisacáridos Bacterianos/genética , Estudios Retrospectivos , Adulto Joven
12.
J Immunol ; 202(2): 441-450, 2019 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-30552163

RESUMEN

Zinc deficiency causes immune dysfunction. In T lymphocytes, hypozincemia promotes thymus atrophy, polarization imbalance, and altered cytokine production. Zinc supplementation is commonly used to boost immune function to prevent infectious diseases in at-risk populations. However, the molecular players involved in zinc homeostasis in lymphocytes are poorly understood. In this paper, we wanted to determine the identity of the transporter responsible for zinc entry into lymphocytes. First, in human Jurkat cells, we characterized the effect of zinc on proliferation and activation and found that zinc supplementation enhances activation when T lymphocytes are stimulated using anti-CD3/anti-CD28 Abs. We show that zinc entry depends on specific pathways to correctly tune the NFAT, NF-κB, and AP-1 activation cascades. Second, we used various human and murine models to characterize the zinc transporter family, Zip, during T cell activation and found that Zip6 was strongly upregulated early during activation. Therefore, we generated a Jurkat Zip6 knockout (KO) line to study how the absence of this transporter affects lymphocyte physiology. We found that although Zip6KO cells showed no altered zinc transport or proliferation under basal conditions, under activation, these KO cells showed deficient zinc transport and a drastically impaired activation program. Our work shows that zinc entry into activated lymphocytes depends on Zip6 and that this transporter is essential for the correct function of the cellular activation machinery.


Asunto(s)
Proteínas de Transporte de Catión/metabolismo , Síndromes de Inmunodeficiencia/metabolismo , Proteínas de Neoplasias/metabolismo , Linfocitos T/inmunología , Timo/patología , Zinc/metabolismo , Animales , Atrofia , Transporte Biológico , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/inmunología , Proliferación Celular , Citocinas/metabolismo , Técnicas de Silenciamiento del Gen , Humanos , Células Jurkat , Activación de Linfocitos , Ratones , Ratones Endogámicos C57BL , Modelos Animales , FN-kappa B/metabolismo , Factores de Transcripción NFATC/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/inmunología , Transducción de Señal , Factor de Transcripción AP-1/metabolismo , Regulación hacia Arriba
13.
Artículo en Francés | RSDM | ID: biblio-1348829

RESUMEN

Contexte : L'épidémie du virus de l'immunodéficience humaine au Mozambique est un problème grave de santé publique et le Ministère de la Santé a étendu le traitement antirétroviral à tous les districts du pays. Cependant, on constate un nombre élevé d'abandon du traitement encore insuffisamment évalué. L'Organisation Mondiale de la Santé recommande que les tradipraticiens de santé collaborent avec les systèmes nationaux de santé dans les pays en développement, pour combattre cette épidémie, mais il existe peu d'actions dans ce domaine à ce jour. Objectif : Évaluer la connaissance des tradipraticiens sur l'infection et leur disponibilité à coopérer avec les services de santé dans la Province de Nampula au Mozambique, pour améliorer les résultats du traitement antirétroviral. Lieux : Cinq centres de santé des districts de la Province de Nampula, au Nord du Mozambique, avec des taux élevés d'incidence du virus d'immunodéficience humaine et d'abandon du traitement.Méthodes : Une étude mixte transversale, utilisant des interviews ciblés et des discussions de groupes focaux. Les données quantitatives étaient traitées par fréquence et les données qualitatives par analyse de discours et ethnographie locale. Résultats : Nous avons interviewé 79 tradipraticiens de santé. La perte de poids était souvent considérée comme le signal principal de suspicion d'infection par le virus d'immunodéficience humaine et certains tradipraticiens ne pas les signes de la maladie ; la majorité pensait que les antirétroviraux améliorent la qualité de vie des patients, ne prétendait pas traiter l'infection, savait qu'elle n'est pas curable, avait une idée sur le concept de bonne adhésion au traitement et référait les cas compliqués au centre de santé. En ce qui concerne l'alimentation, la moitié considérait exclusivement les céréales comme l'aliment principal ; les fruits étaient importants pour un quart ; l'eau potable est ignorée. La majorité était prête à collaborer avec le système de santé et avait des propositions de coopération pratique : la qualification et la reconnaissance individuelle et la formation intégrée avec les professionnels de santé. Conclusion : Les tradipraticiens connaissaient l'infection par le virus d'immunodéficience humaine et les facteurs associés, mais il y a des lacunes. Ils ont signalé qu'ils utilisaient principalement les plantes médicinales, ce qui peut contribuer au traitement des infections opportunistes et la majorité référait déjà des patients au centre de santé ; mais la collaboration nécessite une procédure éducative et une articulation structurée. Les lacunes de connaissance empêchent une coopération efficace dans le combat contre l'épidémie. Le groupe est disponible pour coopérer avec le système de santé pour améliorer les résultats du traitement antirétroviral, mais pour ça il est nécessaire d'informer et former les tradipraticiens dans un processus intégré de collaboration avec les professionnels de santé conventionnels.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Infecciones por VIH/tratamiento farmacológico , Medicinas Tradicionales Africanas , Fármacos Anti-VIH/uso terapéutico , Antirretrovirales , Plantas Medicinales , Infecciones por VIH/terapia , Antirretrovirales/farmacología , Países en Desarrollo , Cumplimiento de la Medicación , Epidemias/prevención & control , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Antropología Cultural , Mozambique/epidemiología
14.
J Clin Immunol ; 38(4): 503-512, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29855752

RESUMEN

PURPOSE: Subcutaneous immunoglobulin replacement therapy (IgRT) may be administered once a week with a pump or every other day with a syringe (rapid push). The objective of the study was to compare the impact of pump and rapid push infusions on patient's life quality index (LQI). METHODS: This study was a randomized, crossover, multicenter, non-inferiority trial conducted in adults with primary immunodeficiency (PID) accustomed to weekly infusions at home by pump. Patients used pump or rapid push for 3 months each according to the randomized sequence. Main criterion was PID-LQI factor I (treatment interference). Non-inferiority ratio was set at 90%. RESULTS: Thirty patients entered the study; 28 completed the two periods. IgRT exposure was similar during each period. At the end of each period, mean LQI factor 1 was 87.0 (IC95% [80.3; 94.3]) and 77.80 (IC95% [71.5; 84.7]) for pump and rapid push, respectively. There was a slightly larger effect of rapid push on treatment interference than with pump so that the primary endpoint could not be met. No difference was found on other LQI components, satisfaction (TSQM), or quality of life (SF36v2). Eight patients declared to prefer rapid push while 19 others preferred pump. Of rapid push infusions, 67.2% led to local reactions vs 71.8% of pump infusions (p = 0.11) illustrating its good tolerance. Rapid push and pump infusions achieved similar trough IgG levels with similar incidence of infections. Rapid push saved 70% of administration cost when compared to pump. CONCLUSIONS: Since IgRT is a lifelong treatment in PID patients, individualization of treatment is of paramount importance. Rapid push is a new administration method in the physician's armamentarium which is preferred by some patients and is cost-effective. CLINICALTRIALS. GOV IDENTIFIER: NCT02180763 CLINICAL IMPLICATIONS: Self-administration of small volumes of immunoglobulins at home, every other day, using a syringe (rapid push) is a cost-effective alternative to administration of larger volumes by pump once a week. This study compared subcutaneous infusions of immunoglobulins either weekly via a pump or every other day via a syringe (rapid push). Rapid push is preferred by some patients and is cost-effective, therefore completing a physician's armamentarium.


Asunto(s)
Inmunoglobulinas/administración & dosificación , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Bombas de Infusión , Infusiones Subcutáneas , Adulto , Anciano , Estudios Cruzados , Femenino , Humanos , Inmunoglobulina G/administración & dosificación , Inmunoglobulina G/efectos adversos , Inmunoglobulinas/efectos adversos , Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/diagnóstico , Masculino , Persona de Mediana Edad , Calidad de Vida , Resultado del Tratamiento , Adulto Joven
15.
Am J Hum Genet ; 102(6): 1126-1142, 2018 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-29805043

RESUMEN

The proteasome processes proteins to facilitate immune recognition and host defense. When inherently defective, it can lead to aberrant immunity resulting in a dysregulated response that can cause autoimmunity and/or autoinflammation. Biallelic or digenic loss-of-function variants in some of the proteasome subunits have been described as causing a primary immunodeficiency disease that manifests as a severe dysregulatory syndrome: chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE). Proteasome maturation protein (POMP) is a chaperone for proteasome assembly and is critical for the incorporation of catalytic subunits into the proteasome. Here, we characterize and describe POMP-related autoinflammation and immune dysregulation disease (PRAID) discovered in two unrelated individuals with a unique constellation of early-onset combined immunodeficiency, inflammatory neutrophilic dermatosis, and autoimmunity. We also begin to delineate a complex genetic mechanism whereby de novo heterozygous frameshift variants in the penultimate exon of POMP escape nonsense-mediated mRNA decay (NMD) and result in a truncated protein that perturbs proteasome assembly by a dominant-negative mechanism. To our knowledge, this mechanism has not been reported in any primary immunodeficiencies, autoinflammatory syndromes, or autoimmune diseases. Here, we define a unique hypo- and hyper-immune phenotype and report an immune dysregulation syndrome caused by frameshift mutations that escape NMD.


Asunto(s)
Predisposición Genética a la Enfermedad , Chaperonas Moleculares/genética , Mutación/genética , Degradación de ARNm Mediada por Codón sin Sentido/genética , Secuencia de Bases , Línea Celular , Estrés del Retículo Endoplásmico , Exones/genética , Familia , Mutación del Sistema de Lectura/genética , Heterocigoto , Humanos , Síndromes de Inmunodeficiencia/genética , Inmunofenotipificación , Recién Nacido , Inflamación/patología , Interferón Tipo I/metabolismo , Masculino , Proteínas Mutantes/metabolismo , Fenotipo , Complejo de la Endopetidasa Proteasomal/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Síndrome , Respuesta de Proteína Desplegada
17.
Hematol Oncol Clin North Am ; 31(5): 823-834, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28895850

RESUMEN

Transfer of gene-corrected autologous hematopoietic stem cells in patients with primary immunodeficiencies has emerged as a new therapeutic approach. Patients with various conditions lacking a suitable donor have been treated with retroviral vectors and a gene-addition strategy. Initial promising results were shadowed by the occurrence of malignancies in some of these patients. Current trials, developed in the last decade, use safer viral vectors to overcome the risk of genotoxicity and have led to improved clinical outcomes. This review reflects the progresses made in specific disorders, including adenosine deaminase deficiency, X-linked severe combined immunodeficiency, chronic granulomatous disease, and Wiskott-Aldrich syndrome.


Asunto(s)
Terapia Genética , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/terapia , Animales , Ensayos Clínicos como Asunto , Evaluación Preclínica de Medicamentos , Expresión Génica , Terapia Genética/efectos adversos , Terapia Genética/métodos , Vectores Genéticos/clasificación , Vectores Genéticos/genética , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Humanos , Transducción Genética , Transgenes , Acondicionamiento Pretrasplante/métodos
19.
Curr Opin Rheumatol ; 29(4): 348-354, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28379860

RESUMEN

PURPOSE OF REVIEW: In the present review, recent findings regarding silicone breast implants (SBIs) complicated by rheumatic autoimmune diseases are described. RECENT FINDINGS: Despite changes in the principal constituents of the silicone implants during the past 50 years, silicone remained an adjuvant that may 'bleed' and subsequently may be a chronic stimulus to the immune system resulting in similar clinical manifestations as 50 years ago. Silicones are spread throughout the body and can be detected in tissues and the central nervous system. Autoimmune/inflammatory syndrome by adjuvants (ASIA), allergies, autoimmune diseases, immune deficiencies and lymphomas occur in patients with SBIs. There is a need for adequately adjusted epidemiological studies to ascertain the frequency of these diseases. Explantation of the breast implants, however, should be advised to patients with complaints, as 60-80% of patients show an amelioration of the signs and symptoms after explantation. SUMMARY: SBIs are associated in a proportion of patients with complaints such as fatigue, cognitive impairment, arthralgias, myalgias, pyrexia, dry eyes and dry mouth. Silicones can migrate from the implant through the body and can induce a chronic inflammatory process. Explantation of SBI results in the majority of patients in an amelioration of the symptoms.


Asunto(s)
Adyuvantes Inmunológicos , Enfermedades Autoinmunes/epidemiología , Implantes de Mama , Hipersensibilidad/epidemiología , Síndromes de Inmunodeficiencia/epidemiología , Inflamación/epidemiología , Linfoma/epidemiología , Enfermedades Reumáticas/epidemiología , Siliconas , Humanos , Factores de Riesgo , Síndrome
20.
Pharm Biol ; 55(1): 1358-1367, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28303736

RESUMEN

CONTEXT: Chronic stress is an inevitable factor in the modern day society which affects cell mediated as well as humoral immunity. There is a need to prevent stress effects with traditionally used herbs. OBJECTIVE: The present study was undertaken to investigate the immunoprotective effect of Vacha (Acorus calamus L. Acoraceae) rhizome under stressful condition. MATERIALS AND METHODS: Soxlet extraction of Vacha rhizome was performed with increasing polarity of solvents, i.e., petroleum ether to ethanol. The extract was concentrated by distilling off the solvent in flash evaporator and dried in desiccators. The benzene extract was found to have anti-stress property in our earlier studies and hence it was used in the present experiment. Extract was administered every day for 4 weeks orally to adult female rats prior to exposure to stress, restraint (1 h) and forced swimming exercise (15 min). RESULTS: Vacha rhizome extract significantly prevented the stress induced reduction in total and differential leukocytes count, immunoglobulin content, bone marrow cellularity and viability, lymphocytes counts in lymphoid organs, islands of white pulp of spleen (ED50 = 10 mg, p < 0.001) and a significant increase in circulating immune complexes and apoptotic index of lymphoid organs (ED50 = 10 mg, p < 0.001) compared to controls. DISCUSSION AND CONCLUSION: The present study clearly indicates that Vacha extract not only prevents stress-induced suppression of immunity and structural involution of lymphoid organs, but also boosts immunity in normal rats. Therefore, it is suggested that Vacha extract administration maintains normal immunity despite the body experiencing stress.


Asunto(s)
Acorus , Síndromes de Inmunodeficiencia/prevención & control , Fitoterapia , Extractos Vegetales/uso terapéutico , Estrés Psicológico/inmunología , Animales , Apoptosis/efectos de los fármacos , Peso Corporal , Femenino , Células Madre Hematopoyéticas/efectos de los fármacos , Tamaño de los Órganos , Sustancias Protectoras/farmacología , Ratas , Ratas Wistar , Rizoma
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