Implementation of a fully digital histology course in the anatomical teaching curriculum during COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, many medical schools are forced to switch courses of the mandatory curriculum to online teaching formats. However, little information about feasibility and effectiveness is available yet about distance teaching in anatomy. The aim of this study was to evaluate the implementation of a histology course previously taught in a classroom setting into an online-only format based on video conference software. METHODS: Our course design included theoretical introductions, an online-adaptation of virtual microscopy used previously in the classroom, and active learning elements such as collaborative learning in breakout rooms, annotation assignments and multiple-choice questions. Two preclinical semester cohorts of around 400 second and third semester students were taught in histology in parallel courses, using the Zoom software platform. We analyzed data about student attendance during the course, summative quantitative and qualitative evaluation of the students and results of a written test required to pass the course. RESULTS: We observed that student attendance was high and stable during the 19 course days for both second and third semester, and only few students reported technical problems. There were no significant differences in examination results of second semester compared to the third semester, an unexpected result as the third semester already participated in the dissection course before. Similarly, no significant gender-related effects on the examination performance could be noted in both semesters. However, the age of students was negatively correlated with test scores in the second and third semester. Importantly, the overall evaluation of the digital version of the histology course was at least as positive as the in-person version over the past years. CONCLUSION: Together, we experienced that the implementation of a curricular histology course in an online-format is technically realizable, effective and well accepted among students. We also observed that availability and prior experience with digitized specimen in virtual microscopy facilitates transition into an online-only setting. Thus, our study supports the positive potential of distance learning for teaching anatomy during and after COVID-19 pandemic but also emphasizes the need for a synchronous learning environment with partially personnel-intensive small group settings to overcome passivity and inequality aspects, and to foster active learning elements.

Resultado de los primeros tratamientos por Video Laparoscopia del Cáncer de Colon. Hospital Central "Dr. Emilio Cubas". Instituto de Previsión Social. / Result of the first treatments for Video Laparoscopy Colon Cancer. Hospital Central "Dr. Emilio Cubas". Instituto de Previsión Social.

Introducción: El cáncer de colon es la tercera neoplasia más común y la segunda causa de mortalidad por cáncer en los países desarrollados. Las técnicas nuevas para el tratamiento del cáncer de colon como video laparoscopia deben producir mejores resultados clínicos que los de la técnica convencional para llegar a convertirse en una alternativa aceptable. Objetivo: Caracterizar los resultados obtenidos con el tratamiento por video laparoscopia en pacientes con cáncer de colon en el Servicio de Cirugía General de Hospital Central "Dr. Emilio Cubas" del Instituto de Previsión Social, de enero 2008 a julio 2013. Metodología: Estudio observacional descriptivo, de corte transversal; en pacientes internados con diagnóstico de cáncer de colon que fueron sometidos al tratamiento quirúrgico por la técnica video laparoscópica. Resultados: Fueron evaluados 30 pacientes, siendo el 53,33% de sexo femenino, con un promedio de edad de 61 años. La localización más frecuente fue el colon sigmoides con 33,33%. La sigmoidectomia fue la cirugía más efectuada en 33,33% de los pacientes. Se presentó complicación de la cirugía video laparoscópica en el 16,67% de los casos, éstas fueron: sangrado, dehiscencia y complicaciones clínicas; siendo la localización más frecuente el cáncer ciego. Conclusión: Esta técnica es de reciente aplicación en la Institución, cuya ventaja radica en la disminución de las infecciones del sitio quirúrgico, pudiendo de esta manera reducir el costo con respecto al tratamiento convencional. Palabras claves: Neoplasias del colon - Laparoscopía - Paraguay

Introduction: Colon cancer is the third most common malignancy and the second leading cause of cancer mortality in developed countries. Video laparoscopy techniques should produce better clinical results over conventional technique results if it is to eventually become an acceptable alternative in the treatment of colon cancer. Objective: To characterize the results obtained by video laparoscopy treatment of colon cancer at the Department of General Surgery at the Central Hospital "Dr. Emilio Cubas" of the Institute for Social Welfare, from January 2008 to July 2013 Methods: This was a descriptive, observational and cross-sectional study, performed in patients who were hospitalized with a diagnosis of colon cancer and who underwent surgical treatment for cancer using video laparoscopic technique. Results: A total of 30 patients were included in this study, with 53,33% being female, and an average age of 61 years. The most frequent location of the cancer was the sigmoid colon (33,33%). Sigmoid colon resection was the most common procedure performed (33,33% of patients). Complications of video laparoscopic surgery occurred in 16,67% of cases, the most common were bleeding, dehiscence and non-surgical complications; the most common cancer site was the cecum. Conclusion: This newly-implemented technique in our institution hasthe advantage of a decrease in surgical site infections, thusreducing the cost compared to conventional treatment. Keywords: Colonic Neoplasms- Laparoscopy ­Paraguay

Diagnostico Histopatológico en Pacientes con Carcinoma de Endometrio / Histopathological Diagnosis in Patients with Endometrium Carcinoma

Introducción: El carcinoma de endometrio es la neoplasia ginecológica más común, representa el 5% de todos los cánceres que se presentan en la mujer, de ahí radica la importancia de tener en cuenta los factores de riesgo epidemiológicos asociados. Objetivo: Caracterizar a los pacientes con Carcinoma Endometrial según criterios histopatológicos en el Servicio de Anatomía Patológica del Hospital Central del Instituto de Previsión Social, entre los años 2007 y 2012. Metodología: Diseño observacional descriptivo, de corte transversal. Se tuvieron en cuenta el legrado uterino preoperatorio, la existencia de hiperplasia, el material remitido, el tipo histológico, el grado tumoral y el estadio de la enfermedad, según la Federación Internacional de Ginecología y Obstetricia. Fueron incluidas 91 pacientes con una mediana de edad de 64 años, con legrado preoperatorio, diagnóstico por congelación y diagnóstico definitivo de carcinoma de endometrio. Resultados: El 92,4% del legrado preoperatorio coincidió con el diagnóstico final de la pieza quirúrgica de carcinoma endometrial; el 89,0% de casos correspondió a un adenocarcinoma de tipo endometrioide; el 40,0% presentó hiperplasia concomitante al tumor; el 52,7% correspondió al Grado II y el 77,8% se encontró en Estadio I. Conclusión: El diagnóstico preoperatorio por legrado de los pacientes con carcinoma de endometrio, tuvo una precisión aceptable en comparación con el diagnóstico posoperatorio de la pieza quirúrgica. Los resultados sugieren que un diagnóstico patológico completo pre, per y posoperatorio constituyen una necesidad imperiosa para la estadificación, asegurando el beneficio en pos de un mejor manejo de las pacientes. Palabras clave: Neoplasias Endometriales, Legrado, Estadificación de Neoplasias, Secciones por Congelación

Introduction: Endometrial carcinoma is the most common gynecologic malignancy, representing 5% of all cancers that occur in women, therein lies the importance of taking into account the epidemiological factors associated with increased risk for this disease. Objective: To characterize patients diagnosed with Endometrial Carcinoma according to histopathological criteria in patients evaluated at the "Hospital Central del Instituto de Prevision Social" (HC-IPS) between 2007 and 2012. Methods: This was an observational, descriptive, and cross-sectional study. We evaluated preoperative curettage, the existence of hyperplasia, the material submitted, histologic type, tumor grade and stage of the disease, according to the International Federation of Gynecology and Obstetrics. Ninety- one patients were included in the study, with a median age of 64 years. All had preoperative curettage, diagnosis by frozen specimen and definitive diagnosis of endometrial carcinoma. Results: 92,4% of preoperative curettage coincided with the final diagnosis of endometrial carcinoma, 89,0% of cases corresponded to an endometrioid adenocarcinoma, 40,0% had hyperplasia concomitant tumor, 52,7% corresponded to Grade II and 77,8% were at Stage I (FIGO). Conclusion: The preoperative diagnosis by curettage, in patients with endometrial carcinoma had acceptable accuracy compared to the postoperative diagnosis using the surgical specimen. The results suggest that a complete pathological diagnosis pre, peri and postoperative are required for accurate staging and to ensure better patient management. Keywords: Endometrial Neoplasms, Curettage, Frozen Sections.

Conocimiento, actitud y práctica sobre medidas de odontología preventiva en odontólogos: vi Congreso Paraguayo de Endodoncia, 2011 / Knowledge, attitude and practice on preventive measures in dentistry: vi congress Praguayan of Endodontics, 2011

Objetivo: Describir nivel de conocimiento, actitud y práctica de medidas básicas de prevención en salud oral en odontólogos que asistieron al VI Congreso Paraguayo de Endodoncia en el año 2011.Metodología: Estudio transversal, a través de una encuesta autoaplicada validada que contenía preguntas básicas referentes a Odontología Preventiva. Resultados: Participaron del estudio 173 profesionales, con una mediana de 33 años,62,4% con 1 a 12 años de ejercicio en la profesión y 58,4% procedían de universidades públicas.El 57,8% de los encuestados demostró tener muy buenos niveles de conocimiento,de actitud en el 46,8%y38,2%en práctica.La aplicación de medidas de prevención produjo en el 64,2% de los encuestados satisfacción personal. Respecto a las medidas de control de placa, las técnicas más difundidas fueron:cepillado de Bass 80,4%,método del lazo para el hilo dental 53,8% y el flúor se aplica en el 76,9% en su presentación de enjuagues bucales. Se encontró una fuerte asociación entre el conocimiento y la actitud (OR=4,3;p<0,0001) y entre la actitud y la práctica (OR=2,3;p=0,0162) Conclusión: La práctica de la filosofía preventiva se halla condicionada por la actitud y ésta a su vez depende del conocimiento constituyéndose componentes esenciales para la mejora del estado de salud de una población. Palabras claves: Conocimiento, Odontología Preventiva, Odontólogos.

Objective: To describe the level of knowledge, attitude and practice of basic preventive measures in oral health acquired by dentists who attended the VI Paraguayan Congress of Endodontics in 2011. Methods: Cross-sectional study by a validated self-administered survey containing basic questions regarding to Preventive Dentistry. Results: The study comprised 173 professionals, with an average age of 33 years old, 62.4 % with 1-12 years of practice in the profession and almost 58.4 % were from public universities. Whatsmore, 57.8 % of respondents proved to have very good levels of knowledge, 46.8 % of them proved it in attitude and 38.2 % in practice. The application of preventive measures gave to 64.2% of respondents a personal satisfaction. Concerning plaque control measures, the most widely used techniques were: 80.4 % Bass brushing, 53.8 % in a method to tie dental floss and fluoride applies to 76.9% in its presentation of rinses mouth. Furthermore, it has been found a strong association between attitude and practice (OR = 2.3, p = 0.0162) and between knowledge and attitude (p < 0.0001 OR = 4.3) Conclusion: the practice of prevention philosophy is based on the attitude and this in turn depends on knowledge. Therefore, attitude and knowledge are essential components in order to improve the health status of a population. Keywords: Knowledge, Preventive Dentistry, Dental.

Estenosis Hipertrófica Pilórica en menores de 2 meses / Hypertrophic pyloric stenosis in children under 2 months age

Introducción: La estenosis hipertrófica del píloro es uno de los trastornos quirúrgicos más frecuentes en las obstrucciones digestivas en el recién nacido. Las complicaciones que se presentan ponen en riesgo la vida del infante por lo que es importante el diagnóstico y la corrección precoz. Objetivo: Caracterizar la estenosis hipertrófica congénita del píloro en menores de 2 meses atendidos en el Servicio de Cirugía Infantil del Hospital Central del Instituto de Previsión Social, en el periodo comprendido entre los años 2006 y 2012. Metodología: En un estudio observacional descriptivo de corte transversal fueron evaluados 30 casos, tratados quirúrgicamente mediante la técnica de Ramsted­Fredet, las variables estudiadas fueron sexo, edad en semanas,tiempo transcurrido para el diagnóstico, métodos de diagnóstico, consulta previa, alteración y tiempo de corrección del medio interno. Resultados: La frecuencia de la patología fue 20,4%, con una edad promedio de 4,5 semanas. El 86,7% de los afectados fueron del sexo masculino y el 63,3% de los pacientes pertenecieron al área de Gran Asunción. El 70,0% de los casos eran primogénitos. La oliva pilórica pudo ser palpada en el 66,7% de los casos. Los lactantes obtuvieron buena respuesta al esquema terapéutico de corrección del medio interno logrado a las 24 horas en el 56,7%. No se presentaron complicaciones post quirúrgicas. Conclusión: El riesgo que conlleva esta patología y la efectiva solución quirúrgica determina la importancia del diagnóstico temprano, a fin de instaurar un adecuado tratamiento; por ello es importante promover el conocimiento en el personal médico en el primer anillo de consulta del niño. Palabras clave: Píloro, Vómitos, Lactante.

Introduction: Hypertrophic pyloric stenosis is one of the most common surgical disorders in digestive blockages in the newborn. Complications arise threatening the infant's life, so early diagnosis and correction is significant. Objective: To characterize congenital hypertrophic pyloric stenosis in children under 2 months age seen at the Department of Paediatric Surgery, Central Hospital of Social Security Institute, in the period between 2006 and 2012. Methodology: A descriptive cross-sectional study, were evaluated 30 cases surgically treated by the technique of Ramsted - Fredet , the variables studied were sex, age in weeks , time to diagnosis, diagnostic methods, previous consulting, alteration and correction time of the internal environment. Results: The frequency of the disorder was 20,4%, with an average age of 4,5 weeks. 86,7% of patients were male and 63,3 % of patients belonged to the Great Asunción area. 70,0 % of cases were first-born. The pyloric olive could be palpated in 66,7% of cases. Infants obtained good therapeutic response with correction scheme of the internal environment, achieved at 24 hours at 56,7%. No postoperative complications. Conclusion: The risk of this pathology and effective surgical solution determines the importance of early diagnosis, in order to begin a correct treatment; so it is important to promote knowledge in the medical staff at the first ring of child consultation. Keywords: Pylorus, Vomiting, Infant.

Odontología, Universidad y Sociedad / Dentistry, University and Society

Las reformas en salud en Latinoamérica han fomentado la privatización de los tratamientos en salud, estando asíel acceso a los servicios acorde al poder adquisitivo del individuo. Actualmente, las patologías bucales representan un problema prioritario en salud pública. Comunidades desfavorecidas económicamente tienden a acumular niveles de salud bucal deteriorados. Para reducir las desigualdades en salud bucal, las estrategias y recursos deben considerar las diferencias entre comunidades, promoviendo la odontología preventiva primaria desde una perspectiva comunitaria; teniendo en cuenta aspectos biológicos, contexto social, cultural, económico, ambiental y acceso a los sistemas de atención en salud. Para ello la educación y el cambio de conducta tienen un papel preponderante. La Universidad como componente de la sociedad, tiene como misión participar en la cultura y aportar soluciones a los problemas sociales, articulando la formación en salud bucal comunitaria con la docencia, investigación y extensión, de manera a formar profesionales orientados en la atención de necesidades de la población. La metodología de la investigación científica debe facilitar y contribuir en la generación de nuevos conocimientos que aporten soluciones concretas al mejoramiento en salud bucal comunitaria. Es preciso emprender nuevos esfuerzos en la formación odontológica a nivel nacional. En tal sentido, se presenta una revisión de los aspectos fundamentales que conciernen a la desigualdad en salud, a la educación como punto de partida para la prevención, a la motivación humana y al cambio de conducta del individuo, incluyendo al rol de la Universidad en la propuesta de soluciones a problemas sociales. Palabras clave: Odontología Comunitaria -Educación en Salud Dental - Odontología Preventiva

Health reforms in Latin America have encouraged the privatization of treatments, thus, access to services are dependent of the individual's purchasing power. Oral pathologies currently represent a public health priority. Economically disadvantaged communities tend to present high levels of impaired oral health. In order to reduce inequalities in oral health, both strategies and resources should consider the differences between communities, promoting primary preventive dentistry from a community perspective, while taking into account biological, social, cultural, economic, and environmental aspects, as well as the access to health care systems. In this regard, education and behavioral changes have a major role. The University, as a component of society, has the mission to participate in culture and provide solutions to social problems, articulating community oral health education with teaching, research and extension, in order to form professionals focused on caring for the needs of the population. Scientific research methodology should facilitate and contribute to the generation of new knowledge that provides concrete solutions for the improvement of community oral health. New efforts on dental training nationwide need to be applied. In this regard, fundamental aspects of health inequality, education as a starting point for prevention, human motivation and individual behavioral change, including the role of the University role in the solution of social problems. Keywords: Community Dentistry -Health Education, Dental - Preventive Dentistry

Common exonic missense variants in the C2 domain of the human KIBRA protein modify lipid binding and cognitive performance.

The human KIBRA gene has been linked to human cognition through a lead intronic single-nucleotide polymorphism (SNP; rs17070145) that is associated with episodic memory performance and the risk to develop Alzheimer's disease. However, it remains unknown how this relates to the function of the KIBRA protein. Here, we identified two common missense SNPs (rs3822660G/T [M734I], rs3822659T/G [S735A]) in exon 15 of the human KIBRA gene to affect cognitive performance, and to be in almost complete linkage disequilibrium with rs17070145. The identified SNPs encode variants of the KIBRA C2 domain with distinct Ca(2+) dependent binding preferences for monophosphorylated phosphatidylinositols likely due to differences in the dynamics and folding of the lipid-binding pocket. Our results further implicate the KIBRA protein in higher brain function and provide direction to the cellular pathways involved.

A new subtype of brachydactyly type B caused by point mutations in the bone morphogenetic protein antagonist NOGGIN.

Brachydactyly type B (BDB) is characterized by terminal deficiency of fingers and toes, which is caused by heterozygous truncating mutations in the receptor tyrosine kinase-like orphan receptor 2 (ROR2) in the majority of patients. In a subset of ROR2-negative patients with BDB, clinically defined by the additional occurrence of proximal symphalangism and carpal synostosis, we identified six different point mutations (P35A, P35S, A36P, E48K, R167G, and P187S) in the bone morphogenetic protein (BMP) antagonist NOGGIN (NOG). In contrast to previously described loss-of-function mutations in NOG, which are known to cause a range of conditions associated with abnormal joint formation but without BDB, the newly identified BDB mutations do not indicate a major loss of function, as suggested by calculation of free-binding energy of the modeled NOG-GDF5 complex and functional analysis of the micromass culture system. Rather, they presumably alter NOG's ability to bind to BMPs and growth-differentiation factors (GDFs) in a subtle way, thus disturbing the intricate balance of BMP signaling. The combined features observed in this phenotypic subtype of BDB argue for a functional connection between BMP and ROR2 signaling and support previous findings of a modulating effect of ROR2 on the BMP-receptor pathway through the formation of a heteromeric complex of the receptors at the cell surface.

Caldendrins in the inner retina.

Caldendrin is the first member of a novel family of Ca2+-binding proteins (CaBPs). Its unique two-domain structure is composed of a calmodulin-homologous teminus and an unrelated N-terminal part. The latter is thought to mediate the tight association of caldendrin with the subsynaptic cytoskeleton. Caldendrin is expressed in forebrain regions with a laminar cytoarchitecture as well as in the inner retina where it is localized to OFF cone bipolar and a subset of amacrine and ganlion cells. In addition, caldendrin is prominently present in processes and synapses of the inner plexiform layer. Thus, caldendrin-immunoreactivity is displayed by ubpopulations of most retinal cell classes, with the exception of glial cells. Caldendrin is most likely involved in dendritic Ca2+-signaling, one of the functions of its close relative, calmodulin. However, several lines of evidence suggest that due to its unique properties caldendrin might not merely substitute for calmodulin. t is speculated that either the specific enrichment in cellular micro-compartments like the postsynaptic cytomatrix, the unique two-domain structure or the altered distribution of surface charges renders caldendrin specific for distinct binding partners or certain Ca2+-triggered signaling events.

Intramolecular interactions regulate SAP97 binding to GKAP.

Membrane-associated guanylate kinase homologs (MAGUKs) are multidomain proteins found to be central organizers of cellular junctions. In this study, we examined the molecular mechanisms that regulate the interaction of the MAGUK SAP97 with its GUK domain binding partner GKAP (GUK-associated protein). The GKAP-GUK interaction is regulated by a series of intramolecular interactions. Specifically, the association of the Src homology 3 (SH3) domain and sequences situated between the SH3 and GUK domains with the GUK domain was found to interfere with GKAP binding. In contrast, N-terminal sequences that precede the first PDZ domain in SAP97, facilitated GKAP binding via its association with the SH3 domain. Utilizing crystal structure data available for PDZ, SH3 and GUK domains, molecular models of SAP97 were generated. These models revealed that SAP97 can exist in a compact U-shaped conformation in which the N-terminal domain folds back and interacts with the SH3 and GUK domains. These models support the biochemical data and provide new insights into how intramolecular interactions may regulate the association of SAP97 with its binding partners.

Immunomodulatory effects of glycine on LPS-treated monocytes: reduced TNF-alpha production and accelerated IL-10 expression.

Cytokines play a pivotal role in the pathogenesis of septic shock. Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) stimulate the progression of septic shock whereas the anti-inflammatory cytokine IL-10 has counterregulative potency. The amino acid glycine (GLY) has been shown to protect against endotoxin shock in the rat by inhibiting TNF-alpha production. In the current study we investigated the role of GLY on lipopolysaccharide (LPS) -induced cell surface marker expression, phagocytosis, and cytokine production on purified monocytes from healthy donors. GLY did not modulate the expression of HLA-DR and CD64 on monocytes, whereas CD11b/CD18 expression (P<0.05) and E. coli phagocytosis (P<0.05) decreased significantly. GLY decreased LPS-induced TNF-alpha production (P<0.01) and increased IL-10 expression of purified monocytes. Similarly, in a whole blood assay, GLY reduced TNF-alpha (P<0.0001) and IL-1beta (P<0.0001) synthesis and increased IL-10 expression (P<0.05) in a dose-dependent manner. The inhibitory effects of GLY were neutralized by strychnine, and the production of IL-10 and TNF-alpha was augmented by anti-IL-10 antibodies. Furthermore, GLY decreased the amount of IL-1beta and TNF-alpha-specific mRNA. Our data indicate that GLY has a potential to be used as an additional immunomodulatory tool in the early phase of sepsis and in different pathophysiological situations related to hypoxia and reperfusion.

Low glutamine concentrations induce phenotypical and functional differentiation of U937 myelomonocytic cells.

L-Glutamine is the most abundant free amino acid of the human body and is essential for the culture of many cell types. Clinically, reduction of glutamine by administration of glutaminase or the use of glutamine analogs is a common therapy for patients with acute lymphocytic leukemia. In the current study, we investigated the influence of glutamine concentrations on the human myelomonocytic cell line U937. Decreasing the glutamine concentration evoked a reduction in DNA synthesis (R2 = 0.9885, P < 0.0001), increased cell volume (P < 0.01) and the cytoplasm/nuclear ratio, and enhanced the development of vacuoles but did not influence cell viability. Culturing cells in reduced concentrations of glutamine augmented the percentage of cells expressing CD64 (Fc receptor for IgG/FcgammaRI, P < 0.01), CD11b (complement receptor type 3/CR3, P < 0.001) and CD71 (transferrin receptor, P < 0.05). The percentage of U937 cells expressing CD23 (low affinity receptor for IgE/FcepsilonRII) was increased at low concentrations of glutamine at both the protein (P < 0.01) and mRNA levels. The percentage of U937 cells phagocytizing opsonized E. coli (P < 0.001) or latex particles (P < 0.001) was enhanced by lowering the glutamine concentration. In conclusion, reducing glutamine concentration causes differentiation of the cell line U937 along the monocytic pathway. These effects may indicate a mechanistic basis for prior published evidence that glutaminase and glutamine antagonists are effective anti-tumor agents.

Effects of 1 alpha,25-dihydroxyvitamin D3 and cytokines on the expression of MHC antigens, complement receptors and other antigens on human blood monocytes and U937 cells: role in cell differentiation, activation and phagocytosis.

The effect of calcitriol/1 alpha,25-dihydroxyvitamin D3, alone and in combination with cytokines, on the expression of various antigens (Ag) on human peripheral blood monocytes and U937 cells was studied by flow cytometry. Both constitutive and interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-6 and tumour necrosis factor-alpha (TNF-alpha)-induced human leucocyte antigen (HLA)-DR, HLA-DP and HLA-DQ Ag expression on monocytes was significantly down-regulated by calcitriol, IL-10 and transforming growth factor-beta (TGF-beta). The effects of calcitriol were concentration dependent and reached maximal inhibitory levels after 3-5 days. Modulation of HLA-DR by calcitriol and IFN-gamma at the protein level correlated with the amount of mRNA specific for the HLA-DR alpha-chain, as judged by Northern blot analysis. The basal as well as IL-4, IL-6, IFN-gamma, TNF-alpha and TGF-beta-driven levels of HLA-ABC Ag were significantly diminished by calcitriol. On U937 cells calcitriol markedly induced CD11a and CD11b expression and weakly up-regulated CD11c whereas on monocytes, constitutive CD11a, CD11b and CD11c expression was significantly down-regulated by calcitriol. The expression of CD14 Ag was strongly induced on U937 cells but only modestly on monocytes. Both the basal level of CD71 and IL-4, IFN-gamma or TNF-alpha-driven expression was diminished on calcitriol-treated U937 cells. In addition, calcitriol suppressed the expression of CD71 Ag on monocytes. The ability of monocytes to phagocytize opsonized Escherichia coli was diminished by calcitriol. Our results demonstrate that calcitriol, alone or in combination with cytokines, modulates expression of MHC, CD11b, CD11c, CD14 and CD71 Ag on both monocytes and U937 cells, and impairs the phagocytic property of monocytes.

A high performance liquid chromatography method for the determination of glycosaminoglycans in human blood.

A method is described for the determination of plasma and serum glycosaminoglycans, which can be used in any laboratory equipped with an HPLC system. It is based on the sequential application of chondroitinases AC and ABC and separation of the resulting disaccharides by high-performance liquid chromatography. All reagents are commercially available. This simple and rapid separation yields an accurate quantification and an exact distribution pattern. The determination of glycosaminoglycan disaccharides is linear between 7 and 7000 mumol/l with coefficients of variation between 3.0 and 7.7% for serum and between 2 and 14% for plasma. The recovery of the assay ranged from 93 to 106% for different concentrations of glycosaminoglycan disaccharides. This HPLC method may therefore be considered as a candidate reference method.