Gc-globulin concentrations and C5 haplotype-tagging polymorphisms contribute to variations in serum activity of complement factor C5.

OBJECTIVES: To investigate the role of Gc-globulin and C5 gene variants as co-factors in the regulation of profibrogenic C5 serum activities. DESIGN: Retrospective clinical investigation with 100 healthy probands. Genomic DNA was isolated from whole blood and examined for the human C5 htSNPs rs17611 and rs2300929. Actin-free Gc-globulin-, total Gc-globulin- and total C5-concentrations in serum were measured using ELISA assays; C5 activities in serum were determined using radial immunodiffusion. RESULTS: C5 serum concentrations were significantly elevated in individuals carrying at least one profibrogenic allele of the C5 htSNP rs17611, but no association between C5 htSNPs and C5 serum activities was detected, albeit C5 activities correlated positively with C5 concentrations in serum. However, C5 activities were also positively correlated with total and actin-free Gc-globulin concentrations. CONCLUSION: Our findings indicate that C5 gene variants and Gc-globulin levels co-define the proinflammatory and profibrogenic effects of C5 in patients at-risk for progression of liver fibrosis.

Argininosuccinate lyase deficiency (ASL) and carbohydrate-deficient transferrin (CDT): experience with four independent CDT analysis methods--misleading results given by the %CDT TIA assay.

BACKGROUND: Chronic liver disease can cause false-positive carbohydrate-deficient transferrin (CDT) results mimicking chronic alcohol abuse. We tested whether argininosuccinate lyase deficiency (ASL), a genetic disorder of the urea cycle with hepatomegaly and biochemical hepatitis, causes increased CDT results and whether this depends on the analytical method. METHODS: Seven serum samples from four ASL patients without alcohol abuse were analyzed by capillary electrophoresis, HPLC, particle-enhanced immunonephelometry with monoclonal CDT antibodies, and microcolumn CDT and non-CDT fractionation followed by a turbidimetric immunoassay with transferrin antibodies (%CDT TIA). RESULTS: Increased CDT results (two out of four patients or five out of seven samples) were obtained by the %CDT TIA assay, but not by the remaining three CDT tests. The corresponding serum samples showed increased fractions of trisialotransferrin by HPLC (as the IFCC reference method for CDT analysis). One sample contained an elevated trisialotransferrin but a normal CDT also in the %CDT TIA test. One patient had a normal trisialotransferrin and a normal CDT as assayed by each of the four CDT methods. CONCLUSIONS: Argininosuccinate lyase deficiency is not itself a cause for increased CDT values. Increased fractions of trisialotransferrin in ASL patients appear to interfere with CDT analysis by the %CDT TIA assay. This can give false-positive CDT results. Since this can appear not only in ASL patients, microcolumn CDT and non-CDT fractionation followed by a turbidimetric immunoassay using transferrin but not CDT antibodies by the %CDT TIA assay should no longer be used for CDT measurement without confirmatory analysis by HPLC or capillary electrophoresis.

Primary biliary cirrhosis is not a clinical condition for increased carbohydrate-deficient transferrin: experience with four independent CDT analysis methods.

BACKGROUND: Primary biliary cirrhosis (PBC) is considered as an important cause for increased carbohydrate-deficient transferrin (CDT). The underlying pathomechanism is difficult to explain by the pathogenesis and/or consequences of PBC. We tested whether PBC causes increased CDT results with current CDT analysis methods and, if so, whether this depends on the CDT analysis principle. METHODS: 48 serum samples from PBC patients were analyzed by HPLC, microcolumn CDT and non-CDT fractionation followed by a turbidimetric immunoassay, particle-enhanced immunonephelometry with monoclonal CDT antibodies, and capillary electrophoresis. The test-specific decision limits were used for categorization of the CDT analysis results into normal and increased values. RESULTS: HPLC: 47 normal/1 increased, microcolumn+TIA: 46 normal/2 increased, particle-enhanced immunonephelometry: 41 normal/7 increased, capillary electrophoresis: 48 normal CDT results. After combining an immunological CDT test (microcolumn+TIA or particle-enhanced immunonephelometry) as the screening method with a physico-chemical CDT test (HPLC or electrophoresis) as the confirmatory method, 1 case remained with increased CDT values by the screening (value 2.6%, cut-off 2.5%, particle-enhanced immunonephelometry) and confirmatory (value 1.8%, cut-off 1.75%, HPLC) analysis. CONCLUSIONS: PBC should no longer be overstressed as an important cause for false-positive CDT results regarding chronic alcohol abuse. In the presence of odd CDT results, PBC should be considered in the anamnestic exploration. However, PBC is not by itself a cause for increased CDT values.

Gc-globulin: roles in response to injury.

BACKGROUND: Gc-globulin (vitamin D-binding protein) appears to have important functions in addition to its role as a carrier of vitamin D. APPROACH: We reviewed recent studies focusing on the pathophysiologic functions and clinical significance of Gc-globulin. RESULTS: Serum concentrations of Gc-globulin, as determined by immunoassay techniques, are decreased in severe injury. The extent of the decrease may have prognostic significance for patient outcomes. Clinical studies and animal models have shown that Gc-globulin has an important role in the clearance of procoagulant actin from the circulation after its release during cell necrosis and tissue injury. Gc-globulin has other potential roles in responses to acute tissue injury through conversion to a macrophage-activating factor, neutrophil chemotactic activity, and enhancement of C5a-mediated signaling. CONCLUSION: Considering the important physiologic roles of Gc-globulin in responses to tissue injury, such as clearance of actin, measurement of Gc-globulin may have value in directing the care of patients in many clinical disorders.

Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin.

BACKGROUND: Recent studies point to the adipose tissue as a highly active endocrine organ secreting a range of hormones. Leptin, ghrelin, adiponectin, and resistin are considered to take part in the regulation of energy metabolism. APPROACH: This review summarizes recent knowledge on leptin and its receptor and on ghrelin, adiponectin, and resistin, and emphasizes their roles in pathobiochemistry and clinical chemistry. CONTENT: Leptin, adiponectin, and resistin are produced by the adipose tissue. The protein leptin, a satiety hormone, regulates appetite and energy balance of the body. Adiponectin could suppress the development of atherosclerosis and liver fibrosis and might play a role as an antiinflammatory hormone. Increased resistin concentrations might cause insulin resistance and thus could link obesity with type II diabetes. Ghrelin is produced in the stomach. In addition to its role in long-term regulation of energy metabolism, it is involved in the short-term regulation of feeding. These hormones have important roles in energy homeostasis, glucose and lipid metabolism, reproduction, cardiovascular function, and immunity. They directly influence other organ systems, including the brain, liver, and skeletal muscle, and are significantly regulated by nutritional status. This newly discovered secretory function has extended the biological relevance of adipose tissue, which is no longer considered as only an energy storage site. SUMMARY: The functional roles, structures, synthesis, analytical aspects, and clinical significance of leptin, ghrelin, adiponectin, and resistin are summarized.

Comparison of three commercial assays for the measurement of 17alpha-hydroxyprogesterone (17alpha-OHPR): limitations of the quality control system.

The measurement of 17alpha-hydroxyprogesterone (17alpha-OHPR) is of value for the diagnosis and management of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. In the central laboratory from 2000 to 2002, we observed, using the assay from the manufacturer DSL, an elevation of the moving average of 17alpha-OHPR concentrations and a number of adrenocorticotropic hormone (ACTH) stimulation tests despite the lack of any changes to the internal and external quality control, of which the criteria were continuously fulfilled. We studied a population of n=49 patients for the measurement of 17alpha-OHPR, with and without extraction, to evaluate the quality of different commercially available radioimmunoassays. The internal and external quality controls were successful in determining 17alpha-OHPR. An excellent measurement and correlation of 17alpha-OHPR was expressed with the assay from the manufacturer IBL without extraction and from the manufacturer DSL with extraction. The quantitative determination of 17alpha-OHPR requires adequate specificity and accuracy of the 17alpha-OHPR radioimmunoassays. The results show that internal and external quality control systems are not sufficient to resolve analytical problems described in this study.

Herpes simplex virus detection in oral mucosa lesions in patients undergoing oncologic therapy.

UNLABELLED: The presence of Herpes Simplex Virus (HSV) has been a frequent detection in gingivitis and ulcerations of oral mucosa in patients undergoing oncologic therapy. In these patients, lesions tend to show atypical clinical patterns, leading to misdiagnosis. OBJECTIVES: To detect HSV, using an ELISA test, in oral lesions of patients under oncologic therapy, to determine localization of these lesions in the oral cavity, to relate their presence with the general diagnosis of the patient and to compare the test results with the previous clinical diagnosis of the lesions. STUDY DESIGN: Thirty lesions where examined in nineteen pediatric patients under oncologic therapy. Direct samples of all lesions were taken and an ELISA test for HSV type I and II was applied to them. General diagnosis of the patients was consigned, as well as localization of the lesions in the oral cavity and clinical diagnosis of them. A database was elaborated with all the information. RESULTS: 33% of lesions were positive to the test, most of them in patients with acute myeloid leukemia. Localization of lesions was not restricted to areas of mucosa attached to periosteum, but also in areas like the dorsum of the tongue. Positive predictivity of clinical diagnosis was 56,25% and negative predictive index was 92,86%. Sensitivity of the test was 90% and specificity was 65%. CONCLUSIONS: It is very important to corroborate clinical diagnosis of gingivitis and ulcerative lesions of the oral cavity of patients under oncologic therapy with laboratory tests, because of the atypical clinical presentation that can lead to misdiagnosis.

Detección del virus herpes simple en lesiones de la mucosa oral en pacientes con terapia oncológica / Herpes simplex virus detection in oral mucosa lesions in patients undergoing oncologic therapy

La presencia de Virus Herpes Simple (VHS) ha sido una detección frecuente en gingivitis y ulceraciones de a mucosa oral en pacientes bajo terapia oncológica. En estos pacientes las lesiones se presentan con patrones clínicos atípicos, lo que lleva a un diagnóstico erróneo.Objetivos: Detectar VHS utilizando un test de ELISA, en lesiones orales de pacientes: sometidos a terapia oncológica, determinar la localización de las Iesiones en la cavidad oral, relacionar su presencia con el diagnóstico general del paciente y comparar los resultados del test con el diagnóstico clínico previo de Ia lesión.Diseño de estudio. Se examinaron 30 lesiones en 19 pacientes pediátricos bajo terapia oncológica. Se tomaron muestras directas de todas las lesiones y se aplicó el test dé ELISA para VHS tipo I y II. Se consignó el diagnóstico general del paciente, ubicación de las lesiones en la cavidad bucal"y el diagnóstico clínico de las lesiones. Se confeccionó una base de datos y estos se relacionaron entre sí.Resultados: Un 33 por ciento de las lesiones fueron pós tivas al test, la mayoría en pacientes can leucemia mieloide aguda. La localización de las lesiones no se limitó a áreas de mucosa adherida a per ostio, ya qué se observaron también en otras zonas como el dorso de la lengua. La predictividad positiva del diagnóstico clínico fue de 56,25 por ciento y el índice predictivo negativo fue de 92,86 por ciento. La sensibilidad del test fue de 90 por ciento y Ia especificidad de 65 por ciento.Conclusiones: Es muy importante corroborar mediante tests de laboratorio el diagnóstico clínico de gingivitis Y lesiones ulcerativas de la cavidad bucal en pacientes con terapia oncológica, ya que la presentación clínica atípica que éstas presentan puede llevar a falsos diagnósticos (AU)

Manifestaciones orales en pacientes pedíátricos con patología oncológica / Oral manifestations in pediatric patients with oncologic pathology

Las neoplasias malignas y su tratamiento producen complicaciones bucales que comprometen al paciente en su estado general. Objetivos: El objetivo de este estudio fue registrar las manifestaciones orales más frecuentes en pacientes pediátricos con patología oncológica, bajo tratamiento. Diseño de estudio: Se realizó un estudio descriptivo de las lesiones bucales registradas en pacientes que se encontraban en período de hospitalización en la Unidad de Oncohematología del Servicio de Pediatría del Hospital Regional de Concepción, Chile, durante un período de dos años. El diagnóstico se realizó en base a un examen clínico, realizado en visitas semanales, con luz artificial, siempre por el mismo operador. Los datos fueron registrados en fichas personales. Se excluyó la patología de tejidos duros. De un total de 127 pacientes, el 59 por ciento era de sexo masculino y el 41 por ciento de sexo femenino. El rango de edad fue de 5 meses a 16 años. El 57 por ciento de los pacientes eran portadores de leucemias o linfomas y el 43 por ciento de otras neoplasias malignas. Resultados: El 65 por ciento de ellos presentó algún tipo de patología bucal. El grupo que presentó mayor porcentaje de patología oral fue el de pacientes portadores de leucemia mieloide aguda (95 por ciento), seguido por los pacientes con linfomas (73 por ciento) y los que padecían de leucemia linfoblástica aguda (71 por ciento). La patología que presentó mayor cantidad de episodios fue la candidiasis (38 por ciento), seguida de mucositis (19 por ciento), lesiones herpéticas (14 por ciento) y síndromes hemorragíparos (10 por ciento). Las candidiasis, lesiones herpéticas y síndromes hemorragíparos fueron más frecuentes en los pacientes con leucemia mieloide aguda y las mucositis en los pacientes con linfomas. Conclusiones: Con estos datos se concluye que es necesaria la incorporación del odontólogo al equipo oncológico en el tratamiento integral de estos pacientes (AU)