RESUMEN
Proteomic methodologies offer a robust approach to identify and quantify thousands of proteins from semen components in both fertile donors and infertile patients. These strategies provide an unprecedented discovery potential, which many research teams are currently exploiting. However, it is essential to follow a suitable experimental design to generate robust data, including proper purification of samples, appropriate technical procedures to increase identification throughput, and data analysis following quality criteria. More than 6000 proteins have been described so far through proteomic analyses in the mature sperm cell, increasing our knowledge on processes involved in sperm function, intercommunication between spermatozoa and seminal fluid, and the transcriptional origin of the proteins. These data have been complemented with comparative studies to ascertain the potential role of the identified proteins on sperm maturation and functionality, and its impact on infertility. By comparing sperm protein profiles, many proteins involved in the acquisition of fertilizing ability have been identified. Furthermore, altered abundance of specific protein groups has been observed in a wide range of infertile phenotypes, including asthenozoospermia, oligozoospermia, and normozoospermia with unsuccessful assisted reproductive techniques outcomes, leading to the identification of potential clinically useful protein biomarkers. Finally, proteomics has been used to evaluate alterations derived from semen sample processing, which might have an impact on fertility treatments. However, the intrinsic heterogeneity and inter-individual variability of the semen samples have resulted in a relatively low overlap among proteomic reports, highlighting the relevance of combining strategies for data validation and applying strict criteria for proteomic data analysis to obtain reliable results. This mini-review provides an overview of the most critical steps to conduct robust sperm proteomic studies, the most relevant results obtained so far, and potential next steps to increase the impact of sperm proteomic data.
Asunto(s)
Infertilidad Masculina , Oligospermia , Humanos , Masculino , Semen/metabolismo , Proteómica/métodos , Infertilidad Masculina/diagnóstico , Infertilidad Masculina/metabolismo , Espermatozoides/metabolismo , Oligospermia/metabolismo , Proteínas/metabolismoRESUMEN
A 27-year-old female at 20th week of pregnancy was admitted with edema, foamy urine, but normal blood pressure. Her blood count was normal, she had proteinuria of 3 g/day, creatinine 0.4 mg/dl, albumin 2.4 g/dl, and cholesterol 355 mg/dl. Antinuclear antibodies 1/160, but Anti-DNA, anticardiolipin antibodies and lupus anticoagulant were negative, with normal serum C3 and C4. A renal biopsy showed secondary membranous glomerulopathy, most likely lupus class V pure. Steroids, azathioprine, and aspirin were initiated, up to 28 weeks of pregnancy, when she developed severe hypertension, photopsia, headache, anasarca, extensive bruising of the extremities, severe anemia, thrombocytopenia, and creatinine rose to 2.09 mg/dl with preserved diuresis. A female infant, 1045 grams, was delivered by emergency caesarean section. Following the surgery, she experienced diplopia, dysarthria, bradypsychia, and sensory alterations in the lower extremities, necessitating emergency hemodialysis due to pulmonary congestion. Blood smear revealed schistocytes, LDH elevated at 1148 IU/L, while transaminases and liver function remained normal, suggesting thrombotic thrombocytopenic purpura. ADAMTS13 revealed 6% activity with the presence of inhibitor. Mycophenolate and daily plasmapheresis with fresh frozen plasma replacement yielded unsatisfactory response, unaffected by the addition of methylprednisolone pulses and rituximab. Eventually, intravenous cyclophosphamide was introduced, resulting in complete hematological remission and normalization of ADAMTS13, however dialysis-dependence persisted and four years later, right renal cancer prompted bilateral nephrectomy. After a total follow-up of six years, she remained free of neoplastic recurrence and lupus activity, receiving prednisone and hydroxychloroquine. The differential diagnosis of microangiopathic syndrome in a pregnant lupus patient is discussed.
RESUMEN
Cyclosporine (CsA) and tacrolimus (TAC) are immunosuppressant drugs characterized by a narrow therapeutic range and high pharmacokinetic variability. The effect of polymorphisms in genes related to the metabolism and transport of these drugs, namely CYP3A4, CYP3A5, MDR1 and POR genes, has been evaluated in diverse populations. However, the impact of these polymorphisms on drug disposition is not well established in Latin American populations. Using TaqMan® probes, we determined the allelic frequency of seven variants in CYP3A4, CYP3A5, MDR1 and POR in 139 Chilean renal transplant recipients, of which 89 were treated with CsA and 50 with TAC. We tested associations between variants and trough and/or 2-hour concentrations, normalized by dose (C0/D and C2/D) at specific time points post-transplant. We found that CYP3A5*3/*3 carriers required lower doses of TAC. In TAC treated patients, most CYP3A5*3/*3 carriers presented higher C0/D and a high proportion of patients with C0 levels outside the therapeutic range relative to other genotypes. These results reinforce the value of considering CYP3A5 genotypes alongside therapeutic drug monitoring for TAC treated Chilean kidney recipients.
RESUMEN
Objetivo: describir la percepción de los profesionales sanitarios de los diferentes servicios pediátricos de un hospital de Zaragoza acerca de la cultura de seguridad del paciente (SP).Método: estudio descriptivo, observacional, transversal realizado en profesionales de Medicina y Enfermería (n= 345) de servicios de pediatría de un hospital de tercer nivel. Se administró una encuesta sobre cultura de seguridad validada por el Ministerio de Sanidad, Consumo y Bienestar Social. En el análisis estadístico se empleó la prueba de Kruskal Wallis y la t-Student para identificar diferencias entre los profesionales de Medicina y los de Enfermería, asumiendo un nivel de significación p< 0,05.Resultados: participaron un total de 159 profesionales (46,08%). El 71,1% no poseía formación sobre SP. El 40,2% respondió que no existían actividades encaminadas a mejorar la SP, pero un 71,4% afirmaba que sí se activaban medidas ante un suceso para evitar su recurrencia. La mayoría (80,1%) aseguraba trabajar en equipo, pero un 65,4% destacaba la pérdida de información en los cambios de turno. La percepción global de los encuestados sobre la SP en este centro era mayoritariamente Aceptable (54,1%) y Pobre (34,6%). Se observaron diferencias significativas en las secciones de SP: área/unidad de trabajo, jefe/supervisor y comunicación y no en el resto.Conclusiones: más de la mitad de los profesionales tenía una percepción Aceptable de la SP del centro y, en general, no estaban formados sobre la cultura de seguridad ni se identificaba la SP como prioritaria para evitar y prevenir eventos adversos.(AU)
Objective: to describe the perception by healthcare professionals about the different paediatric units of a hospital in Zaragoza in terms of patient safety (PS) culture.Method: a cross-sectional, observational, descriptive study conducted on Medicine and Nursing professionals (n= 345) from Paediatric Units of a Third-Level hospital. A survey on safety culture was conducted, validated by the Ministry of Health, Consumer Affairs and Social Welfare. The Kruskal Wallis and t-Student tests were used during statistical analysis, in order to identify any differences between Medicine and Nursing, with a p< 0.05 significance level.Results: in total, 159 professionals (46.08%) were included; 71.1% had no PS training; 40.2% answered that there were no activities targeted to improving PS, but 71.4% claimed that measures were activated when faced with an event, in order to avoid its recurrence. The majority (80.1%) claimed that they worked as a team, but 65.4% highlighted loss of information in shift changes. The overall perception of the participants about PS in this centre was mostly Acceptable (54.1%) and Poor (34.6%). Significant differences were observed in the PS categories: work area/ unit, head / supervisor, and communication, and not in the rest.Conclusions: over half of professionals had an Acceptable perception of PS in their centre; and overall, they had no training on safety culture, and PS was not identified as a priority to avoid and prevent adverse events.(AU)