ABSTRACT
A sperm that fertilizes an egg has successfully survived multiple checkpoints within the female reproductive tract, termed pre-fertilization events. The leukocytic response is a pre-fertilization event in which sperm trigger an immune response that promotes homing of circulating leukocytes to the uterine lumen to destroy most sperm. Various glycoconjugates decorate the sperm surface, including sialic acids, which are abundant at the sperm surface where they cap most glycan chains and regulate sperm migration through cervical mucus, formation of the sperm oviductal reservoir, and sperm capacitation. However, the role of sperm-associated sialic acids in the leukocytic reaction remains unknown. The cognate endogenous binding partners of sialic acids, sialic acid-binding immunoglobulin-like lectins (Siglecs) play a pivotal role in regulating many immune responses. Here we investigated whether sperm-associated sialic acids inhibit activation of neutrophils, one of the major immune cells involved in the leukocytic reaction. We used in vitro interactions between sperm and neutrophils as well as binding assays between sperm and recombinant Siglec-Fc chimeric proteins to measure interactions. Moreover, we examined whether Siglecs are expressed on human and mouse endometria, which have a role in initiating the leukocytic reaction. Surprisingly less sialylated, capacitated, sperm did not increase neutrophil activation in vitro However, we observed expression of several Siglecs on the endometrium and that these receptors interact with sialylated sperm. Our results indicate that sperm sialic acids may interact with endometrial Siglecs and that these interactions facilitate sperm survival in the face of female immunity.
Subject(s)
Sialic Acid Binding Immunoglobulin-like Lectins/metabolism , Spermatozoa/metabolism , Animals , Endometrium/metabolism , Female , Immunoglobulin Fc Fragments/genetics , Immunoglobulin Fc Fragments/metabolism , Male , Mice , Mice, Inbred C57BL , Neuraminidase/metabolism , Neutrophil Activation , Neutrophils/metabolism , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/isolation & purification , Sialic Acid Binding Immunoglobulin-like Lectins/genetics , Sialic Acids/metabolismABSTRACT
El objetivo del presente es describir los cambios en las distintas tareas realizadas por el auxiliar de farmacia a partir de la implementación del sistema de gestión de la calidad. Se analizaron, estructuraron las tareas de todas las áreas y se desarrollaron manuales de procedimiento. El impacto de la implementación en el trabajo de los Auxiliares de Farmacia del hospital, significó un importante paso en la labor del Servicio.
Subject(s)
Pharmacy Technicians , Total Quality ManagementABSTRACT
OBJECTIVES: To evaluate factors affecting the risk of prostate cancer (CaP) and high-grade disease (HGCaP, Gleason score ≥ 7) in a Mexican referral population, with comparison to the Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator (PCPTRC). METHODS AND MATERIALS: From a retrospective study of 826 patients who underwent prostate biopsy between January 2005 and December 2009 at the Instituto Nacional de Cancerología, Mexico, logistic regression was used to assess the effects of age, prostate-specific antigen (PSA), digital rectal exam (DRE), first-degree family history of CaP, and history of a prior prostate biopsy on CaP and HGCaP, separately. Internal discrimination, goodness-of-fit, and clinical utility of the resulting models were assessed with comparison to the PCPTRC. RESULTS: Rates of both CaP (73.2%) and HGCaP (33.3%) were high among referral patients in this Mexican urology clinic. The PCPTRC generally underestimated the risk of CaP but overestimated the risk of HGCaP. Four factors influencing CaP on biopsy were logPSA, DRE, family history and a prior biopsy history (all P < 0.001). The internal AUC of the logistic model was 0.823 compared with 0.785 of the PCPTRC for CaP (P < 0.001). The same 4 factors were significantly associated with HGCaP as well and the AUC was 0.779 compared with 0.766 of the PCPTRC for HGCaP (P = 0.13). CONCLUSIONS: Lack of screening programs or regular urologic checkups in Mexico imply that men typically first reach specialized clinics with a high cancer risk. This renders diagnostic tools developed on comparatively healthy populations, such as the PCPTRC, of lesser utility. Continued efforts are needed to develop and externally validate new clinical diagnostic tools specific to high-risk referral populations incorporating new biomarkers and more clinical characteristics.
Subject(s)
Ambulatory Care Facilities/statistics & numerical data , Prostate/pathology , Prostatic Neoplasms/pathology , Urology , Aged , Biopsy , Digital Rectal Examination , Family Health , Humans , Logistic Models , Male , Mexico , Middle Aged , Neoplasm Grading , Prognosis , Prostate-Specific Antigen/blood , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/prevention & control , Referral and Consultation/statistics & numerical data , Retrospective Studies , Risk Assessment , Risk FactorsABSTRACT
OBJECTIVES: To perform the first validation study of the finasteride-adjusted Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator (finPCPTRC) in a contemporary referral population in Mexico. METHODS: 837 patients referred to the Instituto Nacional de Cancerología, Mexico City, Mexico, between 2005 and 2009 were used to validate the finPCPTRC by examining various measures of discrimination and calibration. Net benefit curve analysis was used to gain insight into the use of the finPCPTRC for clinical decisions. RESULTS: Prostate cancer (PCa) incidence (72.8%) was high in this Mexican referral cohort and 45.7% of men who were diagnosed with PCa had high-grade lesions (HGPCa, Gleason score >6). 1.3% of the patients were taking finasteride. The finPCPTRC was a superior diagnostic tool compared to prostate-specific antigen alone when discriminating patients with PCa from those without PCa (AUC = 0.784 vs. AUC = 0.687, p < 0.001) and when discriminating patients with HGPCa from those without HGPCa (AUC = 0.768 vs. AUC = 0.739, p < 0.001). The finPCPTRC underestimated the risk of PCa but overestimated the risk of HGPCa (both p < 0.001). Compared with other strategies to opt for biopsy, the net benefit would be larger with utilization of the finPCPTRC for patients accepting higher risks of HGPCa. CONCLUSIONS: Rates of biopsy-detectable PCa and HGPCa were high and 1.3% of this referral cohort in Mexico was taking finasteride. The risks of PCa or HGPCa calculated by the finPCPTRC were not well calibrated for this referral Mexican population and new clinical diagnostic tools are needed.
Subject(s)
5-alpha Reductase Inhibitors/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Finasteride/therapeutic use , Mass Screening/methods , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/drug therapy , Referral and Consultation , Age Factors , Aged , Biopsy , Chi-Square Distribution , Digital Rectal Examination , Genetic Predisposition to Disease , Humans , Incidence , Logistic Models , Male , Mexico/epidemiology , Middle Aged , Multivariate Analysis , Neoplasm Grading , Odds Ratio , Pedigree , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Reproducibility of Results , Retrospective Studies , Risk Assessment , Risk FactorsABSTRACT
BACKGROUND/AIM: We evaluated in diabetic-streptozotocin rats (STZR) the structural changes of glomeruli, preglomerular vessels, glomerular tuft and renal parenchyma in order to determine the degree of renal injury and the presence of remodeling in afferent arterioles developed by diabetes without overimposed hypertension. METHODS: Renal mass index and histological score (glomerular number, density, tubular lesions and degree of arteriosclerosis) were estimated. In afferent arterioles the ratio of wall thickness/lumen was obtained by stereological methods. RESULTS: STZR developed diabetes without hypertension; renal mass index increased and matched changes in glomeruli (decrease of capillary number and enlargement of mesangium and basement capillary membrane). Both glomerular number and density as well as afferent arteriole number were diminished. Degenerative changes in both proximal (glycogenic and hyaline degeneration) and distal tubules (hyaline casts) were also observed. At variance with preglomerular vessels, the efferent arterioles only presented initial arteriosclerosis. Finally, the stereological study of afferent arterioles showed a significantly lower arteriolar lumen area and arteriolar wall thickness in STZR, resulting in a remodeling without modification of wall/lumen ratio. CONCLUSION: Diabetes, uncomplicated by hypertension, is associated with (1) a reduction in glomerular number; (2) degeneration in parenchyma and renal tubules, and (3) a specific pattern of remodeling in preglomerular vessels different from that induced by hypertension. Although this work demonstrated that these changes are not triggered by hypertension, further investigations are required in order to determine which mediators are involved in diabetic-vascular renal dysfunction.
Subject(s)
Atherosclerosis/pathology , Diabetes Mellitus, Experimental/pathology , Diabetic Nephropathies/pathology , Kidney/blood supply , Kidney/pathology , Microcirculation/pathology , Animals , Atherosclerosis/etiology , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/complications , Hypertension/pathology , Kidney/drug effects , Male , Microcirculation/drug effects , Rats , Rats, Sprague-Dawley , StreptozocinABSTRACT
Se revisaron las lesiones linfoproliferativas del tracto gastrointestinal diagnosticadas entre 1963 y 1985 en el Servicio Cátedra de Patología del Hospital Centro de Salud Zenón J. Santillán y otras instituciones de derivación. Se estudió la histopatología de 16 casos de linfomas y seudolinfomas en tubo digestivo, correlacionando los hallazgos morfológicos e inmunohistoquímicos. Para la clasificación de los linfomas no-Hodgkin se utilizaron los parámetros de la Propuesta Internacional de Trabajo (Working Formulation). Los casos se distribuyeron de la siguiente manera: 9 fueron linfomas no-Hodgkin, 6 linfomas Hodgkin y 1 seudolinfoma. El compromiso gástrico se observó en 5 casos; el del intestino delgado en 3; el del intestino grueso en 4; y el del anillo de Waldeyer en 2. En 1 caso de autopsia las lesiones estuvieron presentes en mas de un órgano y en otro solamente en esófago. En todos los casos estudiados se analizó la localización y extensión lesional y la patología mucosa asociada. Cuatro casos (tres L.N.H. y un seudolinfoma) fueron estudiados con inmunohistoquímica, que resultó muy útil como técnica auxiliar de diagnóstico (AU)
Subject(s)
Child, Preschool , Child , Adult , Middle Aged , Aged , Humans , Male , Female , Hodgkin Disease/pathology , Lymphoma/pathology , Digestive System Neoplasms/pathology , Diagnosis, Differential , Hodgkin Disease/diagnosis , Lymphoma/diagnosis , Digestive System Neoplasms/diagnosis , Immunoenzyme TechniquesABSTRACT
Se revisaron las lesiones linfoproliferativas del tracto gastrointestinal diagnosticadas entre 1963 y 1985 en el Servicio Cátedra de Patología del Hospital Centro de Salud Zenón J. Santillán y otras instituciones de derivación. Se estudió la histopatología de 16 casos de linfomas y seudolinfomas en tubo digestivo, correlacionando los hallazgos morfológicos e inmunohistoquímicos. Para la clasificación de los linfomas no-Hodgkin se utilizaron los parámetros de la Propuesta Internacional de Trabajo (Working Formulation). Los casos se distribuyeron de la siguiente manera: 9 fueron linfomas no-Hodgkin, 6 linfomas Hodgkin y 1 seudolinfoma. El compromiso gástrico se observó en 5 casos; el del intestino delgado en 3; el del intestino grueso en 4; y el del anillo de Waldeyer en 2. En 1 caso de autopsia las lesiones estuvieron presentes en mas de un órgano y en otro solamente en esófago. En todos los casos estudiados se analizó la localización y extensión lesional y la patología mucosa asociada. Cuatro casos (tres L.N.H. y un seudolinfoma) fueron estudiados con inmunohistoquímica, que resultó muy útil como técnica auxiliar de diagnóstico
