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Introduction: Imerslund-Gräsbeck syndrome (IGS) is a rare congenital disorder characterized by decreased vitamin B12, megaloblastic anemia, and proteinuria. Clinical case: A 58-year-old woman with four episodes of generalized tonic movements whose paraclinical findings showed cyanocobalamin deficiency. The presence of gait disturbances and constitutional syndrome was reported upon questioning, which required further investigation. The extension tests confirmed type 1 IGS, so it was decided to continue the cyanocobalamin management and nutrition evaluation, with which an adequate evolution was achieved. The patient was eventually discharged. Conclusion: This pathology is low prevalence and mainly affects the first decade of life. It prefers the female sex and is characterized by a decrease in vitamin B12, which can predispose to other disorders such as ataxia and growth retardation.
Introducción: el síndrome de Imerslund-Gräsbeck es un trastorno congénito infrecuente caracterizado por disminución de la vitamina B12, anemia megaloblástica y proteinuria. Caso clínico: mujer de 58 años de edad con cuatro episodios de movimientos tónicos generalizados cuyos paraclínicos mostraban deficiencia de cianocobalamina, por lo que en el interrogatorio se reportaba la presencia de alteraciones en la marcha y síndrome constitucional que requería ampliar los estudios. Los exámenes de extensión confirmaron el síndrome de Imerslund-Gräsbeck tipo 1, de modo que se decidió continuar el manejo con cianocobalamina y valoración con nutrición, con lo que se obtuvo una adecuada evolución y se decidió dar egreso a la paciente. Conclusión: esta patología tiene una baja prevalencia y afecta principalmente a la primera década de la vida, tiene predilección por el sexo femenino y se caracteriza por una disminución de la vitamina B12, que puede predisponer a otras alteraciones como ataxia y retraso en el crecimiento.
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PURPOSE: The 5-fraction scheme (5×5-5.5Gy) is a common High-Dose Rate (HDR) intracavitary brachytherapy regimen for locally advanced cervical cancer (LACC). Yet, its equivalence with Pulse-Dose rate (PDR) schemes remains unproved. The present study aimed at reporting on the outcome of LACC patients treated with 5-fraction HDR brachytherapy. MATERIALS AND METHODS: The medical records of all consecutive patients treated with curative-intent HDR brachytherapy for a LACC in a French Cancer Center were retrospectively reviewed. RESULTS: Thirty-eight LACC patients underwent a 5-fraction intracavitary HDR brachytherapy between 2015 and 2019 (median dose=25Gy/5 fractions, following external-beam radiotherapy). Median age at diagnosis was 60 (range: 29-87). Thirty-one patients (81.5%) underwent concurrent chemotherapy. Tumor stages ranged from 3 IB2 (7.8%), 4 IB3 (10.5%), 4 IIA2 (10.5%), 12 IIB (31.7%), 1 IIIA (2.6%), 2 IIIB (5.3%), 7 IIIC1 (18.5%), 4 IIIC2 (10.5%), 1 IVA (2.6%) (2018 FIGO). Median D90% to CTVHR reached 79.5Gy (EQD2). Median D90% to CTVIR reached 59.5Gy (EQD2). Median Bladder D2cc was 69.8Gy (EQD2). Median Rectum D2cc was 58.3Gy (EQD2). Acute/late grade 3 toxicity was reported in one patient (2.6%). No grade 4-5 toxicity occurred. At a median 38 months follow-up, 10 patients (26.3%) had local (n=7, 18.4%), nodal (n=6, 15.7%) and/or distant (n=7, 18.4%) relapse. Three-year overall survival rate was of 81.6%. CONCLUSION: The 5-fraction HDR scheme was well tolerated even in frail patients. Three-year local control was lower than expected. Treatment (absence of parametrial interstitial implants and use of cervical EBRT boost) and patients' characteristics (age, comorbidities) may explain such results.
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Braquiterapia , Fraccionamiento de la Dosis de Radiación , Neoplasias del Cuello Uterino/terapia , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patologíaRESUMEN
PURPOSE: The aim of the present study was to identify management strategies and outcomes of patients with stage IB1 cervical cancer with high recurrence risk. MATERIALS AND METHODS: Medical files of all consecutive patients treated between 2004 and 2017 with external beam radiotherapy and/or brachytherapy for IB1 cervical cancer, whatever the lymph node status, were retrospectively reviewed. RESULTS: Forty-two patients were included, with a median age of 49.8 years old. Median tumour size, estimated with the initial pelvic magnetic resonance imaging, was 26mm (interquartile range [IQR]=19.5-35). Histological types were mainly squamous cell carcinoma (59.5%) and adenocarcinoma (33.3%). Lymphovascular invasion was reported for 38.1% of patients. Pelvic lymph nodes were involved for eight patients (19.0%). Surgery was performed for 39 patients (92.9%). A neoadjuvant treatment was delivered for 20 patients (47.6%), an adjuvant treatment for 19 patients (45.2%) and an exclusive radiotherapy (with or without chemotherapy) followed by brachytherapy for three patients (7.1%). Pathologic complete response was achieved in 61.5% of patients. With a median follow-up of 5.8 years (IQR=2.6-9.4), five patients (11.9%) experienced a tumour relapse. The five-year disease-free survival was 79.5% (95% confident interval [CI]=66.9-94.4), the five-year overall survival was 87.8% (95% CI=77.2-99.8), and the five-year disease-specific survival was 94.2% (95% CI=86.7-100). CONCLUSION: In current clinical practice, tailored treatments are delivered, and seems to give correct therapeutic index. However, clinical trials are needed to standardise treatment according to patient characteristics and recurrence risk factors.
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Adenocarcinoma/radioterapia , Carcinoma de Células Escamosas/radioterapia , Neoplasias del Cuello Uterino/radioterapia , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adulto , Anciano , Antineoplásicos Alquilantes/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Braquiterapia , Carboplatino/uso terapéutico , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Terapia Combinada , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Femenino , Humanos , Radioisótopos de Iridio/uso terapéutico , Estimación de Kaplan-Meier , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Pronóstico , Radioterapia Adyuvante , Recurrencia , Estudios Retrospectivos , Riesgo , Resultado del Tratamiento , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patologíaRESUMEN
BACKGROUND: Clinical parameters and proteins have recently been suggested as possible causes of radiotherapy (RT) resistance in cervical carcinoma (CC). The objective of the present study was to validate prognostic biomarkers of radiation resistance. METHODS: The present prospective study included patients undergoing RT with curative intent for histologically proven locally advanced squamous cell CC. Tissues and blood samples were systematically collected before RT initiation. Immuno-histochemistry was performed (IGF-IR α and ß, GAPDH, HIF-1 alpha, Survivin, GLUT1, CAIX, hTERT and HKII). Response to radiation was assessed through tumour response 3 months after RT completion, through overall survival (OS) and through progression-free survival (PFS). RESULTS: One hundred forty nine patients with a mean age of 46 years were included, with FIGO IIB (n = 53) and FIGO IIIB (n = 96) CCs. 61 patients were treated with exclusive RT + brachytherapy and 88 underwent chemo-radiotherapy + brachytherapy. Our findings suggest an association between hemoglobin level (Hb) (>11 g/dL) and 3 months complete response (p = 0.02). Hb level < 11 g/dL was associated with decreased PFS (p = 0.05) and OS (p = 0.08). Overexpression of IGF-1R ß was correlated with a decreased OS (p = 0.007). Overexpression of GLUT1 was marginally correlated with reduced OS (p = 0.05). PFS and OS were significantly improved in patients undergoing chemoradiation versus exclusive radiotherapy (PFS: p = 0.04; OS: p = 0.01). CONCLUSIONS: IGF-1R ß overexpression and Hb level (≤11 g/dl) were associated with poor prognosis, and thus appear to be possible interesting biomarkers of radiation resistance. Our results corroborate previous pre-clinical studies suggesting IGF-1R and hypoxia to be part of the biological pathways leading to radio-resistance.
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Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/radioterapia , Tolerancia a Radiación/fisiología , Neoplasias del Cuello Uterino/radioterapia , Adulto , Carcinoma de Células Escamosas/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Radioterapia/métodos , Neoplasias del Cuello Uterino/mortalidadRESUMEN
PURPOSE: Although the large impact of Human papilloma virus (HPV) in cervical cancer is established, its place as a therapeutic target is new and according to the growing literature, could be promising. In the present study, radiosensitivity's difference based on HPV-16 variants is assessed. PATIENTS AND METHODS: Variants of Human papilloma virus were identified before the exclusive radiotherapy in patients with cervical cancer. Data were prospectively collected. Fifty-nine patients were screened. RESULTS: Among the 59 screened patients, 34 (57.6%) were identified to be HPV-16 (+), with 13 European and two non-European variants. Of the 34 patients, 15 experienced exclusive radiotherapy. Among them, eight had complete response (seven with European and one with non-European variants), four with European variant had partial response, three with European variant had tumour persistence and one with non-European variant progressed at 3 months. CONCLUSION: No radiosensitivity difference was established, probably because of the limited population. Non-European variant aggressiveness might be suggested in accordance with the literature, as it was associated with the only tumour progression. Exclusive radiotherapy provides a unique and "pure" model of radioresistance in cervical cancer and could be the missing link between in vitro studies and state of the art chemoradiotherapy studies that probably feature too many parameters to identify radioresistance causes. The present study was a first step, with the future prospects of building a larger cohort study in order to better understand HPV-induced radioresistance and then to be able to propose new made-to-measure treatments.
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Papillomavirus Humano 16 , Infecciones por Papillomavirus/radioterapia , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/virología , Adulto , Anciano , Femenino , Variación Genética , Papillomavirus Humano 16/clasificación , Papillomavirus Humano 16/genética , Humanos , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Clinical manifestations of acute bronchiolitis (AB) vary from minimal disease to severe respiratory failure. The response to respiratory viral infections is possibly influenced by genetic polymorphisms linked to the regulation of the inflammatory response. In the present study, we investigated whether interleukin-8 (IL-8) and interleukin-17 (IL-17) genetic variants are associated with the severity of AB. A group of Brazilian infants hospitalized with AB and a control group (infants with no or mild AB, without hospitalization) were genotyped for four IL-8/IL-17 variations. For replication, we studied an Argentinean population sample of infants with mild and severe AB. IL-8 polymorphism (rs 2227543) and IL-17 (rs2275913) variants showed significant associations with the severity of AB. The effect of the IL-8 variation could be replicated in the Argentinean sample. This finding suggests that IL-8 variations may influence the severity of AB in young infants. Further genetic association studies in low- or middle-income populations are necessary with the aim of expanding knowledge in this area.
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Bronquiolitis Viral/genética , Bronquiolitis Viral/inmunología , Predisposición Genética a la Enfermedad , Interleucina-17/genética , Interleucina-8/genética , Argentina , Brasil , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Humanos , Lactante , Masculino , Polimorfismo de Nucleótido Simple , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVES: To evaluate the effect of dialysable leucocyte extract (DLE) on pro- and anti-inflammatory profiles in a rat model of osteoarthritis (OA). METHOD: Forty-eight male Wistar rats were divided into three groups: normal rats without treatment, OA rats treated with placebo, and OA rats treated with DLE. After treatment, the animals were killed to obtain cartilage for histological analysis and to determine the expression of pro- and anti-inflammatory cytokines by reverse transcription multiplex polymerase chain reaction (RT-MPCR) and immunohistofluorescence analyses. RESULTS: Histological analysis revealed that OA cartilage from rats treated with DLE displayed similar characteristics to non-OA cartilage from the control group. The OA cartilage treated with placebo showed alterations in the cellular architecture and in chondrocyte cluster formation. Analysis of cytokine expression by RT-MPCR showed that OA cartilage from DLE-treated rats expressed platelet-derived growth factor (PDGF), interferon (IFN)-γ, and fibroblast growth factor (FGF)-2, similar to non-OA cartilage from the control group. However, OA cartilage from rats treated with placebo expressed interleukin (IL)-1, PDGF, and I kappa B (IκB). Confocal immunodetection of FGF-2, PDGF, and non-phosphorylated IκB showed that they were distributed in the cytoplasm of most chondrocytes in OA cartilage from DLE-treated rats whereas no nuclear factor kappa B (NF-κB) expression was observed in the nuclei. Instead, in OA cartilage from the placebo group, only weak FGF-2 staining was observed, PDGF and IκB were not detected, and NF-κB was strongly observed in both cytoplasm and nuclei. CONCLUSIONS: Our findings suggest that DLE treatment modifies the OA process, promoting the expression of anti-inflammatory cytokines and diminishing the inflammatory effects, avoiding the nuclear translocation of NF-κB in chondrocytes.
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Artritis Experimental/tratamiento farmacológico , Osteoartritis/tratamiento farmacológico , Factor de Transferencia/uso terapéutico , Animales , Artritis Experimental/metabolismo , Artritis Experimental/patología , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Citocinas/metabolismo , Evaluación Preclínica de Medicamentos , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Proteínas I-kappa B/metabolismo , Masculino , FN-kappa B/metabolismo , Osteoartritis/metabolismo , Osteoartritis/patología , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Ratas Wistar , Factor de Transferencia/farmacologíaRESUMEN
Activation of the growth hormone (GH) secretagogue receptor (GHS-R) by synthetic GH releasing peptides (GHRP) or its endogenous ligand (Ghrelin) stimulates GH release. Though much is known about the signal transduction underlying short-term regulation, there is far less information on the mechanisms that produce long-term effects. In the current report, using an enzyme-linked immunosorbent assay for GH detection and whole-cell patch-clamp recordings, we assessed the long-term actions of such regulatory factors on voltage-activated Ca(2+) currents in bovine somatotropes (BS) separated on a Percoll gradient and detected by immunohistochemistry. After 24 h of treatment with Ghrelin (10 nM) or GHRP-6 (100 nM) enhanced BS secretory activity; GH secretion stimulated by GHS through the activation of GHS-R because treatment with the antagonist of GHS-R (D-Lys3-GHRP-6, 10 µM) blocked the GH secretion, and the effect was dose and time dependent (24, 48, and 72 h). GH secretion stimulated by GHRP-6 was abolished by nifedipine (0.5 µM), a blocker of L-type HVA Ca(2+) channels, and KN-62 (10 µM), an inhibitor of Ca(2+)/CaM-KII. After 72 h in culture, all recorded BS exhibited two main Ca(2+) currents: a low voltage-activated (LVA; T-type) and a high voltage-activated (HVA; mostly dihydropyridine-sensitive L-type) current. Interestingly, HVA and LVA channels were differentially upregulated by Ghrelin. Chronic treatment with the GHS induced a significant selective increase on the Ba(2+) current through HVA Ca(2+) channels, and caused only a small increase of currents through LVA channels. The stimulatory effect on HVA current density was accompanied by an augment in maximal conductance with no apparent changes in the kinetics and the voltage dependence of the Ca(2+) currents, suggesting an increase in the number of functional channels in the cell membrane. Lastly, in consistency with the functional data, quantitative real-time RT-PCR revealed transcripts encoding for the Cav1.2 and Cav1.3 pore-forming subunits of L-type channels. The treatment with Ghrelin significantly increased the Cav1.3 subunit expression, suggeting that the chronic stimulation of the GHS receptor with Ghrelin or GHRP-6 increases the number of voltage-gated Ca(2+) channels at the cell surface of BS.
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Enfermedad Crítica/terapia , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Lesión Renal Aguda/complicaciones , Antioxidantes/metabolismo , Antioxidantes/uso terapéutico , Biomarcadores/sangre , Quemaduras/complicaciones , Cuidados Críticos , Humanos , Hiperglucemia/complicaciones , Macrófagos/metabolismo , Enfermedades Mitocondriales/prevención & control , Neutrófilos/metabolismo , Síndrome de Dificultad Respiratoria/complicaciones , Sepsis/complicacionesRESUMEN
The association of tacrolimus (TAC) and mycophenolate mofetil (MMF) in renal transplant patients has diminished the incidence of acute rejection. We evaluated the use of generic TAC and MMF as primary immunosuppression in 6 living related (LR) and 11 cadaveric (C) donor renal transplant recipients (9 men, 8 women) of mean age 37 +/- 12 years (range, 17-56 years) between May 2006 and June 2007. From day 0 all patients received TAC, MMF, and prednisone without antibody induction. They were followed for the development of acute rejection, graft loss, side effects, and mortality. Mean follow-up was 7.6 months (range, 2-15 months). No biopsy-proven acute rejection episodes, graft loss, or recipient deaths were observed. Creatinine levels at the end of the study were 1.90 +/- 1.0 mg/dL (range, 0.62-4.25 mg/dL for C recipients and 1.19 +/- 0.15 mg/dL (range, 0.91-1.35 mg/dL) for LR recipients. Mean systolic and diastolic blood pressures were 130/73 mm Hg with 12 patients (70.5%) on antihypertensive therapy with calcium antagonists and beta-blockers. Mean (range) of total cholesterol, triglycerides, and glucose were 172 (110-244) mg/dL, 139 (69-277) mg/dL, and 89 (63-129) mg/dL, respectively. MMF was suspended in 1 patient due to diarrhea and 1 other because of leukopenia. We observed that generic TAC and MMF yielded effective and safe immunosuppression in terms of mortality, biopsy-proven acute rejection, and graft loss with a low incidence of adverse effects during the study period.
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Trasplante de Riñón/inmunología , Ácido Micofenólico/análogos & derivados , Tacrolimus/uso terapéutico , Adulto , Cadáver , China , Esquema de Medicación , Quimioterapia Combinada , Medicamentos Genéricos , Femenino , Estudios de Seguimiento , Humanos , Terapia de Inmunosupresión/métodos , Trasplante de Riñón/mortalidad , Donadores Vivos , Masculino , Metilprednisolona/uso terapéutico , Ácido Micofenólico/uso terapéutico , Prednisona/uso terapéutico , Análisis de Supervivencia , Donantes de TejidosRESUMEN
The objective of this study was to investigate circadian variations of blood and milk lead toxicokinetics in dairy cows in summer. Twenty lactating Holstein animals were randomly assigned to four treatments corresponding to different hours after onset of light (HALO): 2, 8, 14, and 20. Cows received a single intravenous administration of 2.5 mg/kg lead as lead acetate. Blood and milk samples were taken and analyzed by atomic absorption spectrophotometry. For each toxicokinetic parameter, a one-way analysis of variance (ANOVA) was performed to outline the existence of daily variations. Significant blood differences as a function of HALO were found for the hybrid constant of distribution (alpha), hybrid constant of elimination (beta), elimination half-life (t(1/2)beta), area under the curve (AUC), volume of distribution at steady state (V(ss)) and clearance (Cl(B)) (p<0.05). Half-life of elimination presented two peaks at 2 and 14 HALO. Milk data showed significant differences for maximum concentration and AUC (p<0.05). The ratio AUC(milk)/AUC(blood) was utilized to estimate penetration of lead in milk. It differed significantly throughout the day (p<0.05). Milk data for the significant parameters could be fitted to circadian rhythms. No circadian rhythms were detected in blood parameters or in the ratio AUC(milk)/AUC(blood).
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Bovinos/metabolismo , Ritmo Circadiano , Plomo/análisis , Leche/química , Compuestos Organometálicos/farmacocinética , Animales , Femenino , Inyecciones Intravenosas , Lactancia/metabolismo , Plomo/sangre , Compuestos Organometálicos/sangre , Farmacocinética , Estaciones del AñoRESUMEN
OBJECTIVE: The purpose of this study was to determine whether nutritional components other than high maternal blood phenylalanine levels (> or = 10 mg/dL) are associated with congenital heart defects in the offspring of women with hyperphenylalaninemia. STUDY DESIGN: Of the 414 subjects who had live births, 249 women (60.1%) started diet treatment before 8 weeks of gestation and had nutritional assessments and infant outcome data. Maternal phenylalanine levels, protein intake, and the incidence of congenital heart defects were determined. Simple contingency table analysis was done by chi(2) and Fisher exact test. RESULTS: A significantly increased incidence of congenital heart defects was observed in offspring of mothers with hyperphenylalaninemia who had an elevated blood phenylalanine level >10 mg/dL at 0 to 8 weeks of gestation and a protein intake of < or = 50% of the recommended dietary allowance (P <.0013). CONCLUSION: An inadequate intake of protein during pregnancy in conjunction with elevated blood phenylalanine levels appear to have an additive effect in the incidence of congenital heart defects in the offspring of women with hyperphenylalaninemia.
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Cardiopatías Congénitas/etiología , Fenilcetonuria Materna/sangre , Fenilcetonurias/sangre , Proteínas en la Dieta/metabolismo , Femenino , Cardiopatías Congénitas/prevención & control , Humanos , Recién Nacido , Fenilcetonuria Materna/dietoterapia , Fenilcetonurias/dietoterapia , EmbarazoRESUMEN
BACKGROUND: Investigators in Italy and Spain have suggested that therapy for patients with phenylketonuria (PKU) may result in essential fatty acid (EFA) deficiency. Objectives of this study were to determine if the diets of patients with PKU in the United States provided adequate EFA intakes and whether patients could form long-chain polyunsaturated fatty acids. METHODS: Patients (1-13 years of age) with classic PKU undergoing therapy and their non-PKU sibling closest in age were compared. Nutrient intakes were calculated from 3-day diet diaries. Fatty acids in plasma and erythrocytes were identified and quantified. Paired t tests compared results for the patients and their non-PKU siblings. RESULTS: Twenty-eight patients and 26 siblings were studied. Mean fat intake was greatest by siblings (34.8 +/- 1.3% of energy) and lowest by Phenyl-Free-fed patients (19.5 +/- 1.2% of energy; P < 0.05). Fat intake (30.4 +/- 1.8% of energy) by Phenex-fed patients did not differ from that of siblings. Percentage of energy ingested as C18:2n-6 and C18:3n-3 did not differ significantly between patients and siblings. No clinically significant, consistent differences were found in fatty acid levels (wt%) in plasma or erythrocytes between patients with PKU and siblings. CONCLUSIONS: No patient in this study exhibited a Holman index of EFA deficiency. Siblings ingested animal protein containing C20:5n-3 and C22:6n-3 fatty acids, and this may account for their greater wt% of these plasma and erythrocyte fatty acids. Because patients with PKU do not ingest fatty acids >C18 but C20:4n-6, C20:5n-3, and C22:6n-3 were found in their plasma and erythrocytes, in vivo synthesis from C18:2n-6 and C18:3n-3 appears to occur. Lack of EFA deficiency in patients in this study may be the result of the use of canola and soy oils containing C18:2n-6 and C18:3n-3 rather than olive oil in the diets.
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Ácidos Grasos Esenciales/administración & dosificación , Ácidos Grasos Esenciales/sangre , Fenilcetonurias/sangre , Adolescente , Niño , Preescolar , Estudios Transversales , Registros de Dieta , Ingestión de Energía , Eritrocitos/química , Ácidos Grasos Esenciales/deficiencia , Femenino , Humanos , Lactante , Masculino , Evaluación Nutricional , Estado Nutricional , Fenilcetonurias/dietoterapiaRESUMEN
The Arabidopsis thaliana flavoprotein AtHAL3a is related to plant growth and salt and osmotic tolerance. AtHAL3a shows sequence homology to the bacterial flavoproteins EpiD and Dfp. EpiD, Dfp, and AtHAL3a are members of the homo-oligomeric flavin-containing Cys decarboxylase (HFCD) protein family. We demonstrate that AtHAL3a catalyzes the decarboxylation of (R)-4'-phospho-N-pantothenoylcysteine to 4'-phosphopantetheine. This key step in coenzyme A biosynthesis is catalyzed in bacteria by the Dfp proteins. Exchange of His-90 of AtHAL3a for Asn led to complete inactivation of the enzyme. Dfp and AtHAL3a are characterized by a shortened substrate binding clamp compared with EpiD. Exchange of the cysteine residue of the conserved ACGD motif of this binding clamp resulted in loss of (R)-4'-phospho-N-pantothenoylcysteine decarboxylase activity. Based on the crystal structures of EpiD H67N with bound substrate peptide and of AtHAL3a, we present a model for the binding of (R)-4'-phospho-N-pantothenoylcysteine to AtHAL3a.
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Proteínas de Arabidopsis , Arabidopsis/química , Coenzima A/biosíntesis , Cisteína/metabolismo , Panteteína/análogos & derivados , Panteteína/metabolismo , Ácido Pantoténico/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Secuencia de Aminoácidos , Sitios de Unión , Carboxiliasas/química , Catálisis , Cromatografía en Gel , Cristalografía por Rayos X , Cisteína/análogos & derivados , Cisteína/química , Electroforesis en Gel de Poliacrilamida , Immunoblotting , Modelos Químicos , Modelos Moleculares , Datos de Secuencia Molecular , Complejos Multienzimáticos/química , Mutagénesis Sitio-Dirigida , Mutación , Oxidorreductasas/química , Ácido Pantoténico/análogos & derivados , Péptido Sintasas/química , Reacción en Cadena de la Polimerasa , Unión Proteica , Conformación Proteica , Sales (Química)/metabolismo , Homología de Secuencia de Aminoácido , Transducción de Señal , Factores de TiempoRESUMEN
BACKGROUND: Women with untreated phenylketonuria (PKU) often have poor reproductive outcomes. OBJECTIVE: We assessed the effects of intakes of major nutrients on plasma phenylalanine concentrations and we measured phenylalanine hydroxylase activity and phenylalanine intakes in pregnant women with PKU. DESIGN: Dietary intakes and plasma phenylalanine concentrations were compared in 4 subject groups defined on the basis of plasma phenylalanine concentrations: group 1 (n = 23), <360 micromol/L by 10 wk gestation and 120-360 micromol/L throughout the remainder of pregnancy; group 2 (n = 46), <600 micromol/L but not <360 micromol/L by 10 wk gestation and 120-600 micromol/L throughout the remainder of pregnancy; group 3 (n = 24), <600 micromol/L by 10 wk gestation but >600 micromol/L at least once thereafter; group 4 (n = 147), never <600 micromol/L. RESULTS: Except in the first trimester, mean intakes of phenylalanine, energy, and fat tended to be greater in group 1 than in the other groups. The mean protein intake of group 1 tended to be greater than that of the other groups. Intakes of protein (P < 0.0001), fat (P < 0.0001), and energy (P < 0.007) were negatively correlated with maternal plasma phenylalanine concentrations. It appeared that genotype did not affect phenylalanine tolerance. CONCLUSIONS: Maternal genotype appeared to have little influence on phenylalanine requirements during the first trimester. Early decline and maintenance of maternal plasma phenylalanine concentrations at <360 micromol/L and mean protein intake greater than the recommended dietary allowance (RDA) with mean energy intake near the RDA resulted in the best reproductive outcomes. Inadequate intakes of protein, fat, and energy may result in elevated plasma phenylalanine concentrations and may contribute to poor reproductive outcomes.
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Grasas de la Dieta/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Fenilalanina Hidroxilasa/metabolismo , Fenilalanina/sangre , Fenilcetonuria Materna/sangre , Registros de Dieta , Ingestión de Energía , Femenino , Genotipo , Humanos , Fenilalanina/administración & dosificación , Fenilcetonuria Materna/enzimología , Fenilcetonuria Materna/genética , Embarazo , Resultado del Embarazo , Aumento de PesoRESUMEN
UNLABELLED: The Maternal Phenylketonuria Study began in 1984 and during the intervening years, 572 pregnancies in hyperphenylalaninemic women and 99 controls and their outcomes have been evaluated. Among hyperphenylalaninemic women who delivered a live infant, only 15.9% were treated and in metabolic control preconceptually, however, another 18.4% were in control by 10 weeks. Compared to the results reported by Lenke and Levy in 1980, there is a marked improvement in outcome with treatment. Microcephaly was unusual in preconceptually treated pregnancies with well controlled phenylalanine restricted diets. Even in pregnancies that established control after conception but before the 8th week, congenital heart disease did not occur in the offspring, however, it did occur in 12% of pregnancies not achieving control until after 10 weeks of pregnancy. CONCLUSION: The recommended level of blood phenylalanine during pregnancy is 120-360 mumol/l. Best results were obtained by close cooperation between the attending obstetrician and a metabolic team experienced in the care of persons with phenylketonuria.
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Fenilcetonuria Materna , Adulto , Anomalías Congénitas/etiología , Femenino , Genotipo , Humanos , Fenilalanina/administración & dosificación , Fenilalanina/sangre , Fenilcetonuria Materna/sangre , Fenilcetonuria Materna/complicaciones , Fenilcetonuria Materna/dietoterapia , Fenilcetonuria Materna/genética , Embarazo , Resultado del Embarazo , InvestigaciónRESUMEN
D-003 is a mixture of higher aliphatic primary acids purified from sugar cane wax (Saccharum officinarum) with cholesterol-lowering and antiplatelet effects experimentally proven. The present work reports the results of two studies investigating the acute and subchronic oral toxicity of D-003 in rats. Oral acute toxicity of D-003 (2000 mg/kg) was investigated according to the Acute Toxic Class (ATC) method (an alternative for the classical LD(50) test), which was performed in Wistar rats. The results obtained in this study defined D-003 oral acute toxicity as unclassified. In the subchronic study, rats of both sexes were orally treated with D-003 at 50, 200 and 1250 mg/kg for 90 days. At this time, animals were sacrificed. No evidence of treatment-related toxicity was detected during the study. Thus, data analysis of body weight gain, food consumption, clinical observations, blood biochemical, haematology, organ weight ratios and histopathological findings did not show significant differences between control and treated groups. It is concluded that D-003 orally administered to rats was safe and that no drug-related toxicity was detected even at the highest doses investigated in both acute (2000 mg/kg) and subchronic (1250 mg/kg) studies.
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Anticolesterolemiantes/toxicidad , Ácidos Grasos/uso terapéutico , Inhibidores de Agregación Plaquetaria/toxicidad , Administración Oral , Animales , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Dosificación Letal Mediana , Masculino , Ratas , Ratas Sprague-Dawley , Ratas WistarRESUMEN
Con el objeto de investigar la exposición mercurial y estado de salud del personal que labora en el Servicio de Odontología de la Unidad de IPAS-ME Barquisimeto, se realizó un estudio de corte transversal, utilizándose una muestra de cuarenta y siete trabajadores del Servicio de Odontología, lo cual representa un 92 por ciento del total de la población. Para investigar la exposición del metal mercurio en la orina recolectada en 24 horas, se realizaron análisis de laboratorio, además de exámenes complementarios: Hematología completa, Glicemia y pruebas renales y examen físico. Entre los resultados más relevantes se encontró que la población estudiada presentó niveles aceptables de Hg en orina, un 62 por ciento el nivel básico (0,6 mcg/lts), un 17 por ciento cifras entre 07-14 mcgs/lts, un 19 por ciento cifras entre 15.29mcgs/lts, un 2 por ciento en el nivel de intoxicación preclínica no encontrándose valores iguales o mayor a 50 mcgs/lts, el cual se considera como el índice de contaminación mercurial. Cabe destacar que los resultados de valores mercuriales en los ambientes del Servicio de Odontología se ubicaron por debajo de 0,05 mg/m3 de aire, concentración máxima permitida en ambiente de trabajo en Venezuela, por lo tanto se concluye que no existe exposición a la contaminación mercurial en el personal que labora en el Servicio de Odontología de la Unidad IPAS-ME Barquisimeto. Se espera que con los resultados obtenidos se elaboren y apliquien programas preventivos sobre la contaminación mercurial, con la finalidad de evitar el inicio del proceso de enfermedad debido a la falta de información sobre las normas de higiene mercurial
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Humanos , Masculino , Femenino , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Personal de Salud , Mercurio , Estudios Transversales , Amalgama Dental , Exposición Profesional/estadística & datos numéricos , Estado de Salud , Mercurio , VenezuelaRESUMEN
Descriptive, qualitative data was collected from 30 women who participated in the Centers for Disease Control and Prevention-funded Perinatal HIV Reduction and Education Demonstration Activities (PHREDA) Project. Women were primarily heterosexual, welfare-dependent, African-American mothers. Staff trained women to conduct HIV/STD education as peer volunteers. The theory-based educational components consisted of role model stories developed by women about their experiences with HIV/STDs and discussion groups to build behavioral and communication skills. Women were given role-model stories and safer sex supplies to initiate conversations about women's health and sexual safety in their communities. PHREDA groups allowed women to identify their risk reduction, sexual, and family issues. Role model stories provided a validating medium through which high-risk women explored reproductive health risk and planned steps toward behavioral change. Descriptive data from peer volunteers can provide an important perspective on small group, peer-based community HIV/STD reduction interventions.
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Infecciones por VIH/prevención & control , Educación en Salud , Grupo Paritario , Enfermedades de Transmisión Sexual/prevención & control , Mujeres , Negro o Afroamericano , Condones , Empleo , Femenino , Educación en Salud/métodos , Heterosexualidad , Humanos , Motivación , Paridad , Embarazo , Vivienda Popular , Factores de Riesgo , Autoimagen , Conducta SexualRESUMEN
OBJECTIVES: The objectives of this study were to determine if Phenex-1, amino-acid modified medical food with iron maintained normal indices of protein status in infants with phenylketonuria (PKU) and to investigate factors that influence plasma amino acid concentrations. METHODS: A study was conducted for six months in 35 infants with classical PKU diagnosed in the neonatal period. Diet diaries and plasma amino acid concentrations were obtained monthly. Blood for analysis of plasma albumin, blood urea nitrogen (BUN), retinol binding protein (RBP) and transthyretin was obtained at one, three and six months of study. RESULTS: Mean (+/-SEM) total daily intake of medical food and nutrients was 79+/-4 g; 17.3+/-0.6 g protein, 660+/-18 kcal, 255+/-10 mg phenylalanine (Phe), and 1423+/-56 mg tyrosine (Tyr). Mean concentrations of plasma amino acids, except cystine (during entire study), glycine (first month) and Phe were in the normal range. Mean concentrations of plasma Phe were in the treatment range (120 to 360 micromol/L). Plasma concentrations of arginine, methionine, Phe, tryptophan, Tyr, and valine were positively correlated with intakes at various months of study. Concentrations of aspartic and glutamic acids, Phe, and Tyr were positively correlated and 17 amino acids were negatively correlated with the interval between feeding and blood draw. At six months of study, concentration of plasma albumin was 4.1+/-0.1 g/dL, RBP was 3.74+/-0.2 mg/dL, transthyretin was 17.9+/-0.9 mg/dL, and urea nitrogen was 11.9+/-0.5 mg/dL. CONCLUSION: During study, all mean plasma indices of protein status were in normal reference ranges. Phenex-1 supports normal mean plasma amino acid, albumin, RBP, transthyretin, and BUN concentrations when fed in adequate amounts.