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1.
Pediatr Nephrol ; 39(8): 2459-2465, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38589699

RESUMO

BACKGROUND: Hemolytic uremic syndrome (HUS) is an important cause of acute kidney injury in children. HUS is known as an acute disease followed by complete recovery, but patients may present with kidney abnormalities after long periods of time. This study evaluates the long-term outcome of Shiga toxin-producing Escherichia coli-associated HUS (STEC-HUS) in pediatric patients, 10 years after the acute phase of disease to identify risk factors for long-term sequelae. METHODS: Over a 6-year period, 619 patients under 18 years of age with HUS (490 STEC-positive, 79%) were registered in Austria and Germany. Long-term follow-up data of 138 STEC-HUS-patients were available after 10 years for analysis. RESULTS: A total of 66% (n = 91, 95% CI 0.57-0.73) of patients fully recovered showing no sequelae after 10 years. An additional 34% (n = 47, 95% CI 0.27-0.43) presented either with decreased glomerular filtration rate (24%), proteinuria (23%), hypertension (17%), or neurological symptoms (3%). Thirty had sequelae 1 year after STEC-HUS, and the rest presented abnormalities unprecedented at the 2-year (n = 2), 3-year (n = 3), 5-year (n = 3), or 10-year (n = 9) follow-up. A total of 17 patients (36.2%) without kidney abnormalities at the 1-year follow-up presented with either proteinuria, hypertension, or decreased eGFR in subsequent follow-up visits. Patients needing extracorporeal treatments during the acute phase were at higher risk of presenting symptoms after 10 years (p < 0.05). CONCLUSIONS: Patients with STEC-HUS should undergo regular follow-up, for a minimum of 10 years following their index presentation, due to the risk of long-term sequelae of their disease. An initial critical illness, marked by need of kidney replacement therapy or plasma treatment may help predict poor long-term outcome.


Assuntos
Infecções por Escherichia coli , Síndrome Hemolítico-Urêmica , Escherichia coli Shiga Toxigênica , Humanos , Síndrome Hemolítico-Urêmica/microbiologia , Síndrome Hemolítico-Urêmica/terapia , Síndrome Hemolítico-Urêmica/complicações , Síndrome Hemolítico-Urêmica/epidemiologia , Escherichia coli Shiga Toxigênica/isolamento & purificação , Masculino , Feminino , Criança , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/complicações , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/diagnóstico , Pré-Escolar , Seguimentos , Adolescente , Lactente , Alemanha/epidemiologia , Fatores de Risco , Taxa de Filtração Glomerular , Áustria/epidemiologia , Fatores de Tempo , Proteinúria/etiologia , Proteinúria/microbiologia , Proteinúria/diagnóstico
2.
Microorganisms ; 11(8)2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37630548

RESUMO

The use of particles to develop vaccines and treatments for a wide variety of diseases has increased, and their success has been demonstrated in preclinical investigations. Accurately targeting cells and minimizing doses and adverse side effects, while inducing an adequate biological response, are important advantages that particulate systems offer. The most used particulate systems are liposomes and their derivatives, immunostimulatory complexes, virus-like particles, and organic or inorganic nano- and microparticles. Most of these systems have been proven using therapeutic or prophylactic approaches to control tuberculosis, one of the most important infectious diseases worldwide. This article reviews the progress and current state of the use of particles for the administration of TB vaccines and treatments in vitro and in vivo, with a special emphasis on polymeric particles. In addition, we discuss the challenges and benefits of using these particulate systems to provide researchers with an overview of the most promising strategies in current preclinical trials, offering a perspective on their progress to clinical trials.

3.
Pediatr Nephrol ; 38(10): 3435-3443, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37154961

RESUMO

BACKGROUND: Associations between anthropometric measures and patient outcomes in children are inconsistent and mainly based on data at kidney replacement therapy (KRT) initiation. We studied associations of height and body mass index (BMI) with access to kidney transplantation, graft failure, and death during childhood KRT. METHODS: We included patients < 20 years starting KRT in 33 European countries from 1995-2019 with height and weight data recorded to the ESPN/ERA Registry. We defined short stature as height standard deviation scores (SDS) < -1.88 and tall stature as height SDS > 1.88. Underweight, overweight and obesity were calculated using age and sex-specific BMI for height-age criteria. Associations with outcomes were assessed using multivariable Cox models with time-dependent covariates. RESULTS: We included 11,873 patients. Likelihood of transplantation was lower for short (aHR: 0.82, 95% CI: 0.78-0.86), tall (aHR: 0.65, 95% CI: 0.56-0.75), and underweight patients (aHR: 0.79, 95%CI: 0.71-0.87). Compared with normal height, patients with short and tall statures showed higher graft failure risk. All-cause mortality risk was higher in short (aHR: 2.30, 95% CI: 1.92-2.74), but not in tall stature. Underweight (aHR: 1.76, 95% CI: 1.38-2.23) and obese (aHR: 1.49, 95% CI: 1.11-1.99) patients showed higher all-cause mortality risk than normal weight subjects. CONCLUSIONS: Short and tall stature and being underweight were associated with a lower likelihood of receiving a kidney allograft. Mortality risk was higher among pediatric KRT patients with a short stature or those being underweight or obese. Our results highlight the need for careful nutritional management and multidisciplinary approach for these patients. A higher resolution version of the Graphical abstract is available as Supplementary information.


Assuntos
Nanismo , Magreza , Masculino , Feminino , Criança , Humanos , Magreza/epidemiologia , Magreza/complicações , Obesidade/complicações , Índice de Massa Corporal , Terapia de Substituição Renal , Sistema de Registros
4.
Front Plant Sci ; 14: 1101375, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36818889

RESUMO

Heat stress is poised to become a major factor negatively affecting plant performance worldwide. In terms of world food security, increased ambient temperatures are poised to reduce yields in cereals and other economically important crops. Grain amaranths are known to be productive under poor and/or unfavorable growing conditions that significantly affect cereals and other crops. Several physiological and biochemical attributes have been recognized to contribute to this favorable property, including a high water-use efficiency and the activation of a carbon starvation response. This study reports the behavior of the three grain amaranth species to two different stress conditions: short-term exposure to heat shock (HS) conditions using young plants kept in a conditioned growth chamber or long-term cultivation under severe heat stress in greenhouse conditions. The latter involved exposing grain amaranth plants to daylight temperatures that hovered around 50°C, or above, for at least 4 h during the day and to higher than normal nocturnal temperatures for a complete growth cycle in the summer of 2022 in central Mexico. All grain amaranth species showed a high tolerance to HS, demonstrated by a high percentage of recovery after their return to optimal growing conditions. The tolerance observed coincided with increased expression levels of unknown function genes previously shown to be induced by other (a)biotic stress conditions. Included among them were genes coding for RNA-binding and RNA-editing proteins, respectively. HS tolerance was also in accordance with favorable changes in several biochemical parameters usually induced in plants in response to abiotic stresses. Conversely, exposure to a prolonged severe heat stress seriously affected the vegetative and reproductive development of all three grain amaranth species, which yielded little or no seed. The latter data suggested that the usually stress-tolerant grain amaranths are unable to overcome severe heat stress-related damage leading to reproductive failure.

5.
Exp Lung Res ; 48(9-10): 251-265, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36102603

RESUMO

Purpose of the study: During the early and progressive (late) stages of murine experimental pulmonary tuberculosis, the differential activation of macrophages contributes to disease development by controlling bacterial growth and immune regulation. Mycobacterial proteins P27 and PE_PGRS33 can target the mitochondria of macrophages. This study aims to evaluate the effect of both proteins on macrophage activation during mycobacterial infection. Materials and methods: We assess both proteins for mitochondrial oxygen consumption, and morphological changes, as well as bactericide activity, production of metabolites, cytokines, and activation markers in infected MQs. The cell line MH-S was used for all the experiments. Results: We show that P27 and PE_PGRS33 proteins modified mitochondrial dynamics, oxygen consumption, bacilli growth, cytokine production, and some genes that contribute to macrophage alternative activation and mycobacterial intracellular survival. Conclusions: Our findings showed that these bacterial proteins partially contribute to promoting M2 differentiation by altering mitochondrial metabolic activity.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Camundongos , Animais , Ativação de Macrófagos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Macrófagos Alveolares/metabolismo , Mitocôndrias
6.
Environ Monit Assess ; 194(5): 327, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35381961

RESUMO

Fluoride concentrations of 0.5 mg/L in drinking water are considered useful for dental caries prevention. However, fluoride concentrations higher than 1.2 mg/L in water can pose a risk of dental fluorosis due to high exposure to fluoride. The objective is to determine the fluoride concentration in water from aqueducts of different Colombian municipalities of Cauca (Popayán, Coconuco, and Puracé) to assess the fluoride dietary intake from the consumption of this water. A total of 66 water samples have been taken from Popayán, Coconuco, and Puracé. Fluoride content was determined by fluoride ion-selective electrode (ISE) potentiometry. The fluoride concentrations recorded in Coconuco and Puracé water were ≤ 0.002 mg/L. The mean fluoride content recorded in the Popayán water was 0.42 mg/L, with its highest concentration in Cauca River water (0.83 mg/L). Considering the admissible intake values, the water from Popayán confers remarkable fluoride intakes, especially in children with high percentages of contribution to the admissible daily intake (46.7% to 7- to 12-month children and 41.5% to 1- to 3-year children). The fluoride content in the water of Coconuco and Puracé does not reach an optimal value (< 0.5 mg/L) for the protective effect against dental caries, while the water of the main Cauca River basin does reach the optimal value. Likewise, the intake of fluoride from the consumption of the analyzed water does not confer any health risk. However, the implementation of monitoring systems for fluoride levels is recommended in order to safeguard the consumer's health.


Assuntos
Cárie Dentária , Água Potável , Fluorose Dentária , Criança , Colômbia , Monitoramento Ambiental , Fluoretos/análise , Humanos , Rios , Abastecimento de Água
7.
Front Pediatr ; 9: 635152, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490152

RESUMO

Background: High dose methotrexate (HDMTX) is used for the treatment of pediatric hemato-oncological diseases. HDMTX can induce acute kidney injury in cases of delayed elimination. The use of leucovorin remains the most effective rescue action. Further treatment options are of difficult access in the rare cases where leucovorin fails to prevent renal failure from occurring. Glucarpidase is an effective treatment in cases of methotrexate (MTX) delayed elimination, but cost is high and availability is limited. Charcoal hemoperfusion (CHP) is a very efficient procedure to remove protein-bound drugs, promoting fast MTX elimination, but is rarely considered as a treatment option. Methods: We present three pediatric cases with prolonged exposure to MTX after HDMTX and delayed elimination in which hemoperfusion was performed as rescue treatment for methotrexate intoxication. Results: Charcoal hemoperfusion was performed with positive results and no complications as bridging until glucarpidase was available in two cases and in one case where two doses of glucarpidase led to insufficient reduction of MTX levels. Conclusions: CHP can be considered as a rescue treatment option in MTX intoxication, since it is an effective and safe extracorporeal method for removing MTX, in cases where rescue with leucovorin is insufficient and glucarpidase is not available or while waiting for delivery.

8.
Sci Rep ; 11(1): 446, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33432056

RESUMO

It is known that the harmful presence of the wild cochineal (Dactylopius opuntiae), unlike the fine cochineal (Dactylopius coccus), in prickly pear crops of farmers leads to consider it as one of the major pests for this crop. In this study, we present the implementation of an optical setup that ensures the measurement of the in-vivo fluorescence spectra of wild cochineals ranging in size from 440 to 1190 µm in their natural habitat achieved by developing a reproduction model adopted from available literature. It was observed that in-vivo fluorescence spectra of these insects were comprised in the spectral region of 570-760 nm, showing a proportional dependence between the fluorescence intensity emitted and the cochineal size. In addition, we have considered other spectral parameters to perform the comparison between fluorescence spectra of the different cochineal sizes. These results provide the basis for the development of novel methodologies and equipment aimed towards the early detection of this pest in prickly pear crops from its early growth stages (nymph I and II).

9.
Pediatr Nephrol ; 36(4): 917-925, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33025207

RESUMO

BACKGROUND: The complement factor H antibody (CFH-Ab)-associated hemolytic uremic syndrome (HUS) forms a distinct subgroup within the complement-mediated HUS disease spectrum. The autoimmune nature of this HUS subgroup implies the potential benefit of a targeted immunosuppressive therapy. Data on long-term outcome are scarce. METHODS: This observational study evaluates the clinical outcome of 19 pediatric CFH-Ab HUS patients from disease onset until their 5-year follow-up. RESULTS: All but one relapse occurred during the first 2 years, and patients who had no relapse within the first 6 months were relapse-free until the end of the observation period. Kidney function at disease onset determines long-term kidney function: all individuals with normal kidney function at disease onset had normal kidney function after 5 years, and all patients with reduced kidney function at onset had impaired kidney function at the last follow-up. Level of CFH-Ab titer at disease onset was not correlated with a higher risk of recurrences or worse long-term outcome after 5 years. Resolution of CFH-Ab titers after 5 years was common. CONCLUSIONS: CFH-Ab HUS patients have a varied overall long-term course. Early relapses are common, making close surveillance during the first years essential, regardless of the initial CFH-Ab titer.


Assuntos
Fator H do Complemento/imunologia , Síndrome Hemolítico-Urêmica , Insuficiência Renal , Autoanticorpos , Criança , Doença Crônica , Seguimentos , Síndrome Hemolítico-Urêmica/diagnóstico , Síndrome Hemolítico-Urêmica/terapia , Humanos , Recidiva , Resultado do Tratamento
10.
Vaccine ; 37(38): 5731-5737, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31000412

RESUMO

The persistence of tuberculosis (TB) as one of the top 10 causes of death worldwide, the growing incidence of multidrug-resistant tuberculosis and the controversial efficacy of the Bacille Calmette-Guérin (BCG) vaccine drives the development of new generation multistage vaccines against this disease that can boost BCG-primed immunity. The use of polymeric microparticles for this purpose increases due to their advantages, especially their good safety levels and intrinsic immunostimulant properties. We recently explored and demonstrated the reinforcing and adjuvant potential of starch microparticles (SMPs) that administered intranasally to BCG-primed BALB/c mice, alone or in combination with a recombinant antigen, increased survival rates and induced a reduction of bacterial load in the lungs of mice infected with tuberculosis. Here, we tested the effect of SMPs added to the BCG vaccine as adjuvant to the whole-cell vaccine and investigated their contribution to the improvement of the protective efficacy of subcutaneous vaccination in mice challenged with virulent strains of Mycobacterium tuberculosis. As expected, our results were dependent on the infection strains, showing that virulence is a crucial factor that affects the adjuvant activity of SMPs. Our results also confirm the adjuvant activity of this carbohydrate and its usefulness in diverse vaccination strategies not only for mucosal but also for parenteral administration.


Assuntos
Adjuvantes Imunológicos , Vacina BCG/imunologia , Mycobacterium tuberculosis/imunologia , Amido , Tuberculose/imunologia , Tuberculose/prevenção & controle , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Tuberculose/patologia , Vacinas contra a Tuberculose/imunologia , Virulência
11.
Am J Transplant ; 18(11): 2818-2822, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29962080

RESUMO

Primary focal segmental glomerulosclerosis (FSGS) recurs in up to 55% of patients after kidney transplantation. Herein we report the successful management of recurrent FSGS. A 5-year-old boy with primary FSGS received a deceased donor renal transplant. Immediate and fulminant recurrence of FSGS caused anuric graft failure that was resistant to plasmapheresis and rituximab. After exclusion of structural or immunologic damage to the kidney by repeated biopsies, the allograft was retrieved from the first recipient on day 27 and transplanted into a 52-year-old second recipient who had vascular nephropathy. Immediately after retransplantation, the allograft regained function with excellent graft function persistent now at 3 years after transplant. After 2 years on hemodialysis, the boy was listed for kidney retransplantation. To prevent FSGS recurrence, pretreatment with ofatumumab was performed. Nephrotic range proteinuria still occurred after the second transplantation, which responded, however, to daily plasma exchange in combination with ofatumumab. At 8 months after kidney retransplantation graft function is good. The clinical course supports the hypothesis of a circulating permeability factor in the pathogenesis of FSGS. Successful ofatumumab pretreatment implicates a key role of B cells. Herein we provide a description of successful management of kidney failure by FSGS, carefully avoiding waste of organs.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Glomerulosclerose Segmentar e Focal/cirurgia , Rejeição de Enxerto/prevenção & controle , Transplante de Rim/efeitos adversos , Pré-Escolar , Rejeição de Enxerto/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva
12.
BMC Nephrol ; 19(1): 144, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29907094

RESUMO

BACKGROUND: Arthrogryposis-Renal dysfunction-Cholestasis syndrome (ARC, MIM#208085) is a rare multisystem disease due to mutations in the VPS33B and VIPAR genes, both involved in maintaining apical-basolateral cell polarity. The correlation between mutations and phenotype in the ARC Syndrome is not well described. We report on a 6 year old patient who presented with severe renal Fanconi as first manifestation of ARC related to a combined de novo mutation in the VPS33B gene. CASE PRESENTATION: A 6 year old girl presented during the first year of life with severe renal Fanconi as the first manifestation of ARC-Syndrome. This case presents all defining features of ARC syndrome (including liver, skin and articular manifestations) with predominantly renal impairment at presentation. This novel mutation may be associated with a pronounced renal phenotype in ARC. Furthermore, we report on the successful use of LDL-Apheresis and biliodigestive derivation for treatment of cholestatic pruritus with encouraging results. CONCLUSION: ARC is a heterogeneous disorder with early mortality. This case report contributes to a better understanding of this rare disorder, describes a novel mutation in the VPS33B gene and presents an innovative rescue treatment approach.


Assuntos
Artrogripose/diagnóstico , Artrogripose/terapia , Colestase/diagnóstico , Colestase/terapia , Gerenciamento Clínico , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/terapia , Insuficiência Renal/diagnóstico , Insuficiência Renal/terapia , Índice de Gravidade de Doença , Artrogripose/complicações , Remoção de Componentes Sanguíneos/métodos , Criança , Colestase/complicações , Síndrome de Fanconi/complicações , Feminino , Humanos , Insuficiência Renal/complicações
13.
Nephrol Dial Transplant ; 33(12): 2208-2217, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29481636

RESUMO

Background: We investigated the effects of nutritional vitamin D supplementation on markers of bone and mineral metabolism, i.e. serum levels of fibroblast growth factor 23 (FGF23), Klotho, bone alkaline phosphatase (BAP) and sclerostin, in two cohorts with chronic kidney disease (CKD). Methods: In all, 80 vitamin D-deficient children were selected: 40 with mild to moderate CKD from the ERGO study, a randomized trial of ergocalciferol supplementation [estimated glomerular filtration rate (eGFR) 55 mL/min/1.73 m2], and 40 with advanced CKD from the observational Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study (eGFR 24 mL/min/1.73 m2). In each study, vitamin D supplementation was started in 20 children and 20 matched children not receiving vitamin D served as controls. Measures were taken at baseline and after a median period of 8 months. Age- and gender-related standard deviation scores (SDSs) were calculated. Results: Before vitamin D supplementation, children in the ERGO study had normal FGF23 (median 0.31 SDS) and BAP (-0.10 SDS) but decreased Klotho and sclerostin (-0.77 and -1.04 SDS, respectively), whereas 4C patients had increased FGF23 (3.87 SDS), BAP (0.78 SDS) and sclerostin (0.76 SDS) but normal Klotho (-0.27 SDS) levels. Vitamin D supplementation further increased FGF23 in 4C but not in ERGO patients. Serum Klotho and sclerostin normalized with vitamin D supplementation in ERGO but remained unchanged in 4C patients. BAP levels were unchanged in all patients. In the total cohort, significant effects of vitamin D supplementation were noted for Klotho at eGFR 40-70 mL/min/1.73 m2. Conclusions: Vitamin D supplementation normalized Klotho and sclerostin in children with mild to moderate CKD but further increased FGF23 in advanced CKD.


Assuntos
Fosfatase Alcalina/sangue , Densidade Óssea/fisiologia , Suplementos Nutricionais , Fatores de Crescimento de Fibroblastos/sangue , Insuficiência Renal Crônica/terapia , Vitamina D/administração & dosagem , Adolescente , Biomarcadores/metabolismo , Criança , Método Duplo-Cego , Feminino , Fator de Crescimento de Fibroblastos 23 , Seguimentos , Taxa de Filtração Glomerular , Humanos , Masculino , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/fisiopatologia , Vitaminas/administração & dosagem
14.
Tuberculosis (Edinb) ; 106: 106-117, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28802397

RESUMO

Antimicrobial peptides (AMPs) are mainly produced by epithelial cells and macrophages to eliminate infecting mycobacteria through direct antimicrobial activity and immunomodulation. Indeed, it has been described that this line of defense is essential to control infection. However, Mycobacterium tuberculosis (Mtb) has developed mechanisms to avoid AMPs activity, for instance lysX adds lysine residues to surface phospholipids changing their net charge, leading to the repelling of the AMPs. In the present study, we determined that lysX gene is differentially expressed among Mtb strains. To achieve this aim we used several well-characterized Mtb clinical isolates, lysX mutated strains and reference strains. Our results showed that in the presence of AMPs, lysX expression increased significantly. Strains with higher lysX expression showed increased levels of intracellular survival in vivo and in vitro and induced more severe lesion related with pneumonia. Results showed that ability of Mtb to replicate intracellularly was directly correlated to the level of lysX expression showing that the amount of lysX produced by the bacterial cell is an important variable for the modulation of Mtb virulence.


Assuntos
Proteínas de Bactérias/genética , Lisina-tRNA Ligase/genética , Mutação , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidade , Tuberculose Pulmonar/microbiologia , Células A549 , Animais , Peptídeos Catiônicos Antimicrobianos , Antituberculosos/farmacologia , Proteínas de Bactérias/metabolismo , Catelicidinas/genética , Catelicidinas/metabolismo , Catelicidinas/farmacologia , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Regulação Bacteriana da Expressão Gênica , Genótipo , Interações Hospedeiro-Patógeno , Humanos , Pulmão/metabolismo , Pulmão/microbiologia , Lisina-tRNA Ligase/metabolismo , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos Endogâmicos BALB C , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/crescimento & desenvolvimento , Fagocitose , Fenótipo , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/metabolismo , Virulência , beta-Defensinas/genética , beta-Defensinas/metabolismo
15.
Kidney Int ; 92(6): 1507-1514, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28729033

RESUMO

Recent studies in adult chronic kidney disease (CKD) suggest that metabolic acidosis is associated with faster decline in estimated glomerular filtration rate (eGFR). Alkali therapies improve the course of kidney disease. Here we investigated the prevalence and determinants of abnormal serum bicarbonate values and whether metabolic acidosis may be deleterious to children with CKD. Associations between follow-up serum bicarbonate levels categorized as under 18, 18 to under 22, and 22 or more mmol/l and CKD outcomes in 704 children in the Cardiovascular Comorbidity in Children with CKD Study, a prospective cohort of pediatric patients with CKD stages 3-5, were studied. The eGFR and serum bicarbonate were measured every six months. At baseline, the median eGFR was 27 ml/min/1.73m2 and median serum bicarbonate level 21 mmol/l. During a median follow-up of 3.3 years, the prevalence of metabolic acidosis (serum bicarbonate under 22 mmol/l) was 43%, 60%, and 45% in CKD stages 3, 4, and 5, respectively. In multivariable analysis, the presence of metabolic acidosis as a time-varying covariate was significantly associated with log serum parathyroid hormone through the entire follow-up, but no association with longitudinal growth was found. A total of 211 patients reached the composite endpoint (ESRD or 50% decline in eGFR). In a multivariable Cox model, children with time-varying serum bicarbonate under 18 mmol/l had a significantly higher risk of CKD progression compared to those with a serum bicarbonate of 22 or more mmol/l (adjusted hazard ratio 2.44; 95% confidence interval 1.43-4.15). Thus, metabolic acidosis is a common complication in pediatric patients with CKD and may be a risk factor for secondary hyperparathyroidism and kidney disease progression.


Assuntos
Acidose/epidemiologia , Bicarbonatos/sangue , Hiperparatireoidismo Secundário/epidemiologia , Insuficiência Renal Crônica/sangue , Acidose/sangue , Acidose/etiologia , Adolescente , Criança , Progressão da Doença , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/etiologia , Masculino , Prevalência , Modelos de Riscos Proporcionais , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Fatores de Risco
16.
J Clin Apher ; 32(6): 494-500, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28485072

RESUMO

BACKGROUND: Therapeutic plasma exchange (TPE) has evolved to an accepted therapy for selected indications. However, it is technically challenging in children. Moreover, data on safety and efficacy are mainly derived from adult series. The aim of this study was to review the procedure in the context of clinical indications, effectiveness, and safety. STUDY DESIGN AND METHODS: All TPE procedures performed at a tertiary care hospital during a 12-year period (2005-2016) were retrospectively evaluated. RESULTS: Eighteen patients with a median age of 8.5 (0.2-17) years underwent a total of 280 TPE sessions. Eleven (61%) patients were treated for renal diseases. Three (17%) patients were diagnosed with neurological diseases, two had liver failure, and one patient each had sepsis and stem cell transplant-associated thrombotic microangiopathy. Seven patients (39%) were classified as American Society for Apheresis Category I, four (22%) as Category II, two (13%) each as Category III and IV, and two (13%) were not classified. Two patients with atypical hemolytic-uremic syndrome received TPE as long-term therapy over 2 and 5 years. All procedures were performed using the filtration technique and heparin anticoagulation. Twelve (67%) patients showed full or partial recovery after TPE, six had no response or an uncertain response. Minor adverse events occurred in 30/280 (10.6%) procedures, and one major complication (0.4%) was reported. CONCLUSION: TPE is a safe apheresis method in children, even when performed as a long-term therapy. Efficacy is high under selected conditions. A highly skilled and experienced staff is mandatory to ensure patient safety and efficacy.


Assuntos
Troca Plasmática/normas , Adolescente , Remoção de Componentes Sanguíneos , Criança , Pré-Escolar , Filtração , Heparina/uso terapêutico , Humanos , Lactente , Troca Plasmática/efeitos adversos , Indução de Remissão , Estudos Retrospectivos , Centros de Atenção Terciária , Resultado do Tratamento
17.
Immunol Invest ; 46(1): 48-58, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27618158

RESUMO

Aging is a major health issue due to the increased susceptibility of elderly people to infectious, autoimmune, and cardiovascular diseases. Innate immunity is an important mechanism to avoid primary infections; therefore, decreasing of its activity may lead to development of infections. Antimicrobial peptides (AMPs) are effector molecules of innate immunity that can eliminate microbial invaders. The role that cytokines play in the regulation of these innate immune mechanisms needs to be explored. Serum determinations of Th1, Th2, and Th17 cytokines were performed in order to evaluate their association with AMPs human beta-defensin (HBD)-2 and LL-37 in young adults, elder adults, and elder adults with recurrent infections. Our results showed differences in interleukin (IL)-10 and IL-6 among the different groups. Inverse correlations in serum cytokine levels and HBD-2 production were identified for IL-10, IL-2, IL-4, tumor necrosis factor-α, and IL-6. Also inverse correlations were identified for IL-10, IL-4, and cathelicidin (LL-37). Such results could impact the development of immunomodulators that promote AMP production to prevent and/or contain infectious diseases in this population.


Assuntos
Envelhecimento/imunologia , Peptídeos Catiônicos Antimicrobianos/metabolismo , Infecções/imunologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , beta-Defensinas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Peptídeos Catiônicos Antimicrobianos/sangue , Células Cultivadas , Citocinas/metabolismo , Humanos , Imunidade Inata , Pessoa de Meia-Idade , Recidiva , Adulto Jovem , Catelicidinas
18.
Microb Pathog ; 97: 148-53, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27263098

RESUMO

Diabetes mellitus (DM)-2 patients have an increased susceptibility to develop pulmonary tuberculosis; this is partly due to the impairment of the innate immunity because of their higher glucose concentrations. In the present study, we determined the effect of the glucose concentrations in the LL-37 expression in infected and non-infected macrophages. Our results showed that the increasing glucose concentrations correlates with the low cathelicidin expression in non-infected cells, however in Mycobacterium tuberculosis infected cells, LL-37 expression was substantially increased in higher glucose concentrations, nevertheless the mycobacterial burden also increased, this phenomena can be associated with the cathelicidin immunomodulatory activity. Further evaluation for LL-37 needs to be done to determine whether this peptide can be used as a biomarker of tuberculosis progression in DM2 patients.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Glucose/metabolismo , Macrófagos/imunologia , Mycobacterium tuberculosis/imunologia , Carga Bacteriana , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Células U937 , Catelicidinas
19.
Rev. méd. hondur ; 84(1-2): 41-44, ene.-jun. 2016. ilus
Artigo em Espanhol | LILACS | ID: biblio-847485

RESUMO

Introducción. El prolapso de cúpula vaginal es una complicación común después de la histerectomía vaginal con un impacto negativo en la calidad de vida de las mujeres y se considera una condición frecuente que alcanza un 40% en mujeres multíparas.Se asocia con disfunción urinaria, anorrectal y sexual. Una clara comprensión del mecanismo de apoyo del útero y la vagina es importante para tomar la decisión adecuada de procedimiento correctivo. El factor de riesgo más importante suelen ser defectos preexistentes del diafragma pélvico antes de la histerectomía. Caso Clínico: Se presenta el caso de una paciente de 60 años de edad, quien acude por sensación de cuerpo extraño protruyendo de vagina de 30 años de evolución, el cual ha incrementado paulatinamente de tamaño, con antecedentes de histerectomía vaginal realizada hace 12 años, y levantamiento de cúpula hace 10 años. Al examen ginecológico se observa descenso de pared vaginal anterior hasta 4 cms por fuera del introito vaginal, además, descenso del recto por la cara posterior de la vagina. Se realiza levantamiento de cúpula vaginal, con resolución exitosa del problema. Discusión: El riesgo de prolapso de órganos pélvicos aumenta con la paridad y edad avanzada. La cirugía para corregir dichos defectos de apoyo de órganos pélvicos se ha identificado como factor de riesgo para el desarrollo de esta patología. El manejo debe ser individualizado, teniendo en cuenta la experiencia del cirujano, la edad del paciente, sus comorbilidades, antecedentes de cirugía previa y su vida sexual. Conclusión: No hay consenso sobre el mecanismo del prolapso de cúpula, pero lo que es aceptado por todos es la necesidad de evaluar adecuadamente estas pacientes y ponerse de acuerdo sobre el tipo de cirugía que será adecuado para cada circunstancia...(AU)


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Doenças Urogenitais Femininas , Histerectomia Vaginal/métodos , Prolapso Uterino/diagnóstico por imagem
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