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Alérgenos , Prueba de Desgranulación de los Basófilos , Basófilos , Humanos , Poaceae , Polen , Pruebas CutáneasAsunto(s)
Anafilaxia , Silene , Anafilaxia/diagnóstico , Anafilaxia/etiología , Ingestión de Alimentos , HumanosRESUMEN
BACKGROUND: Obesity and obstructive sleep apnea syndrome (OSA) are highly prevalent and frequently overlapping conditions in children that lead to systemic inflammation, the latter being implicated in the various end-organ morbidities associated with these conditions. AIM: To examine the effects of adenotonsillectomy (T&A) on plasma levels of inflammatory markers in obese children with polysomnographically diagnosed OSA who were prospectively recruited from the community. METHODS: Obese children prospectively diagnosed with OSA, underwent T&A and a second overnight polysomnogram (PSG) after surgery. Plasma fasting morning samples obtained after each of the two PSGs were assayed for multiple inflammatory and metabolic markers including interleukin (IL)-6, IL-18, plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), adiponectin, apelin C, leptin and osteocrin. RESULTS: Out of 122 potential candidates, 100 obese children with OSA completed the study with only one-third exhibiting normalization of their PSG after T&A (that is, apnea-hypopnea index (AHI) ≤1/hour total sleep time). However, overall significant decreases in MCP-1, PAI-1, MMP-9, IL-18 and IL-6, and increases in adropin and osteocrin plasma concentrations occurred after T&A. Several of the T&A-responsive biomarkers exhibited excellent sensitivity and moderate specificity to predict residual OSA (that is, AHI⩾5/hTST). CONCLUSIONS: A defined subset of systemic inflammatory and metabolic biomarkers is reversibly altered in the context of OSA among community-based obese children, further reinforcing the concept on the interactive pro-inflammatory effects of sleep disorders such as OSA and obesity contributing to downstream end-organ morbidities.
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Adenoidectomía , Inflamación/sangre , Obesidad Infantil/sangre , Apnea Obstructiva del Sueño/cirugía , Tonsilectomía , Adiponectina/sangre , Adolescente , Biomarcadores/sangre , Quimiocina CCL2/sangre , Niño , Preescolar , Femenino , Humanos , Inflamación/fisiopatología , Interleucina-18/sangre , Interleucina-6/sangre , Leptina/sangre , Masculino , Metaloproteinasa 9 de la Matriz/sangre , Proteínas Musculares/sangre , Obesidad Infantil/complicaciones , Obesidad Infantil/fisiopatología , Inhibidor 1 de Activador Plasminogénico/sangre , Polisomnografía , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/complicaciones , Factores de Transcripción/sangreRESUMEN
OBJECTIVES: Fat mass ratio (FMR) has been suggested as an objective indicator of abnormal body fat distribution in HIV infection. Although it could provide more comprehensive information on body fat changes than limb fat mass, FMR has scarcely been used in clinical trials examining body fat distribution in HIV-infected patients. METHODS: A subanalysis of a controlled, randomized clinical trial in virologically suppressed HIV-1-infected men switching from zidovudine (ZDV)/lamivudine (3TC) to emtricitabine (FTC)/tenofovir (TDF) versus continuing on ZDV/3TC was carried out. FMR was assessed by dual X-ray absorptiometry (DEXA) for a period of 72 weeks. Lipoatrophy was defined as FMR ≥ 1.5. Multivariate linear regression models for the change in FMR from baseline were fitted. RESULTS: Sixty-five men were randomized and treated (28 in the FTC/TDF arm and 37 in the ZDV/3TC arm), and 57 completed the study (25 and 32 in each arm, respectively). In the FTC/TDF arm, adjusted mean FMR decreased by 0.52 at week 72 (P = 0.014), and in the ZDV/3TC arm it increased by 0.13 (P = 0.491; P between arms = 0.023). Among subjects with lipoatrophy (baseline FMR ≥ 1.5), adjusted FMR decreased by 0.76 (P = 0.003) in the FTC/TDF arm and increased by 0.21 (P = 0.411; P between arms = 0.009) in the ZDV/3TC arm. Baseline FMR and treatment group were significant predictors (P < 0.05) of post-baseline changes in FMR. CONCLUSIONS: Switching from ZDV/3TC to FTC/TDF led to an improvement in FMR, compared with progressive worsening of FMR in subjects receiving ZDV/3TC, showing that fat mass not only increased but was also distributed in a healthier way after the switch.
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Fármacos Anti-VIH/uso terapéutico , Distribución de la Grasa Corporal , Sustitución de Medicamentos , Emtricitabina/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Lamivudine/uso terapéutico , Tenofovir/uso terapéutico , Zidovudina/uso terapéutico , Absorciometría de Fotón , Adulto , Terapia Antirretroviral Altamente Activa , Combinación de Medicamentos , VIH-1 , Humanos , Masculino , Persona de Mediana Edad , Análisis de RegresiónRESUMEN
Introduction: The aim of the study was to improve student skills in writing good-quality synthesis texts through a strategic, self-regulated instruction program aimed at ensuring that students properly activated reading and writing strategies required by the synthesis task. Methods: The sample consisted of 84 university students who were randomly assigned to experimental or control conditions. The experimental group received an instructional program based on the development and self-regulated implementation of reading and writing strategies for producing synthesis texts. The control group received a program involving metacognitive knowledge of various academic text types. Both programs involved eight 60-min sessions, taught by teachers in a compulsory degree subject. For the evaluations, students produced synthesis texts from different source texts. The syntheses were graded considering text product measures: information selection, idea connection, text organization, and holistic quality; and measures of reading (underlining and note-taking) and writing (planning and review) strategies. Results: The results show that the experimental group exhibited greater improvements in synthesis quality and greater improvements in activation of information organization processes, note-taking while reading, and text planning. Discussion: In conclusion, university students can, following implementation of a strategic instructional procedure in the context of a study plan, adapt and re-work their own reading and writing strategies and apply them in a self-regulated manner to synthesis tasks, improving text quality and some of the cognitive processes involved.
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There is no cure for diabetic nephropathy and the molecular mechanisms underlying disease aetiology remain poorly understood. While current paradigms for clinical management of diabetic nephropathy are useful in delaying disease onset and preventing its progression, they do not do so for a significant proportion of diabetic individuals, who eventually end up developing renal failure. Thus, novel therapeutic targets are needed for the treatment and prevention of the disease. MicroRNAs (miRNAs), a class of non-coding RNAs that negatively regulate gene expression, have recently been identified as attractive targets for therapeutic intervention. It is widely recognised that dysregulation of miRNA expression or action contributes to the development of a number of different human diseases, and evidence of a role for miRNAs in the aetiology of diabetic nephropathy is emerging. The discovery that modulation of miRNA expression in vivo is feasible, combined with recent results from successful clinical trials using this technology, opens the way for future novel therapeutic applications. For instance, inhibition of miRNAs that are commonly upregulated in diabetic nephropathy decreases albuminuria and mesangial matrix accumulation in animal models, suggesting that a therapeutic agent against these molecules may help to prevent the development of diabetic nephropathy. Certain challenges, including the development of safe and reliable delivery systems, remain to be overcome before miRNA-based therapeutics become a reality. However, the findings accumulated to date, in conjunction with newly emerging results, are expected to yield novel insights into the complex pathogenesis of diabetic nephropathy, and may eventually lead to the identification of improved therapeutic targets for treatment of this disease.
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Nefropatías Diabéticas/terapia , MicroARNs/genética , Humanos , Modelos Biológicos , Insuficiencia Renal Crónica/terapiaRESUMEN
OBJECTIVES: Lipoatrophy is a long-term adverse effect of some antiretrovirals that affects quality of life, compromises adherence and may limit the clinical impact of HIV treatments. This paper explores the effect of tenofovir/emtricitabine (TDF/FTC) on the amount of limb fat in patients with virological suppression. METHODS: A randomized, prospective clinical trial was performed to compare continuation on a zidovudine/lamivudine (ZDV/3TC)-based regimen with switching to a TDF/FTC-based regimen in terms of the effect on limb fat mass as assessed by DEXA over a 72-week period. RESULTS: Eighty patients were included (39 in the TDF/FTC arm and 41 in the ZDV/3TC arm) and 73 completed the study (37 and 36, respectively). In the switch arm, limb fat increased by a median of 540 g from baseline (P = 0.022), while in the ZDV/3TC arm it decreased by a median of 379 g (P = 0.112; p between groups = 0.007). Subjects with baseline limb fat ≤ 7200 g, previous time on ZDV > 5 years or a body mass index > 25 kg/m(2) experienced higher limb fat gains than other subjects, and these differences were statistically significant. Haemoglobin increased by a median of 1.0 g/dL in the TDF/FTC arm (P < 0.001) and remained unchanged in the ZDV/3TC arm (p between groups = 0.0002). There were no significant differences between groups in other secondary endpoints (body weight, total body and trunk fat content, total body bone mineral density, laboratory parameters, CD4 cell count and viral load). CONCLUSIONS: Switching from a ZDV/3TC-based to a TDF/FTC-based regimen led to a statistically significant improvement in limb fat, in contrast to the progressive loss of limb fat in subjects continuing ZDV/3TC.
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Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa/efectos adversos , Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Síndrome de Lipodistrofia Asociada a VIH/patología , Absorciometría de Fotón , Adenina/efectos adversos , Adenina/análogos & derivados , Adenina/uso terapéutico , Tejido Adiposo/patología , Adulto , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Emtricitabina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Organofosfonatos/efectos adversos , Organofosfonatos/uso terapéutico , Estudios Prospectivos , Tenofovir , Resultado del TratamientoRESUMEN
Application of continuous positive airway pressure (CPAP) during respiratory insufficiency through a helmet interface is not well known in the Pediatric practice. The objective of this paper is to describe the necessary elements for it assembly, management and nursing care. The advantages and disadvantages of helmet compared to other interfaces are also discussed.
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Presión de las Vías Aéreas Positiva Contínua/instrumentación , Insuficiencia Respiratoria/terapia , Enfermedad Aguda , Niño , Diseño de Equipo , Humanos , LactanteRESUMEN
Soil contamination in mining areas is an important environmental concern. In these areas, phytoremediation is often impeded because of the low fertility and pH. Assisted phytoremediation is increasingly being used in polluted areas. Biochar could assist plant growth via enhanced soil fertility. An experiment was performed in a mining soil (RIII) from the mining area of Riotinto (Spain) contaminated with Cu, Pb, Zn and As in order to study: (i) The effects of biochar on soil fertility; (ii) Biochar temperature of preparation effect and (iii) Effect of biochar on phytoremediation potential. A mesocosm experiment was designed using Brassica napus as test specie. Soil (RIII) was treated with rabbit manure biochars prepared at 450⯰C (BM450) and 600⯰C (BM600) at a rate of 10% in mass and incubated for 60 days with or without Brassica napus. Results showed that the combination of BM450 or BM600 with Brassica napus growth decreased the amount of As, Cu, Co, Cr, Se and Pb in the soil. Values of bioaccumulation factor (BAF) for Cd were particularly elevated (>10) in the unamended soil and reached values higher than 1 for other elements, indicating the potential of Brassica napus to accumulate several heavy metals. Translocation Factor (TF) was reduced for Co, Cr, Cd, Cu, Ni, Zn, Pb and As after biochar addition indicating root accumulation of these metals. In all cases, biochar addition increased biomass production. Finally, the addition of BM450 increased GMea index indicating also an improvement on soil quality.
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Biodegradación Ambiental , Carbón Orgánico/química , Minería , Contaminantes del Suelo/química , Animales , Biomasa , Brassica napus/crecimiento & desarrollo , Brassica napus/metabolismo , Estiércol , Metales Pesados/análisis , Suelo , Contaminantes del Suelo/análisis , Contaminantes del Suelo/metabolismo , EspañaRESUMEN
Pyrolysis of organic wastes for biochar preparation has been proved as a useful way of waste management. However, the elevated water content of some organic wastes precludes its use without a drying step before pyrolysis treatment. For this reason, hydrothermal carbonization (HTC) of wet biomass could be an inexpensive alternative management method. The main objective of the present work is to compare the properties of biochars and hydrochars obtained from thermal treatment of pig manure. Biochars were prepared at 300⯰C (BPM300), 450⯰C (BPM450) and 600⯰C (BPM600) and hydrochars were obtained using a pig manure solution (ratio 30:70) that was heated at 200⯰C (HPM200), 220⯰C (HPM220) and 240⯰C (HPM240) during 2â¯h. Characterization of biochar and hydrochar samples showed that pyrolysis led to chars with more aromatic structures and high thermal stability while HTC process originated chars with more aliphatic structures. HPM220 and HPM240 showed the highest values of field capacity water content and available water probably due to their higher O/C ratios and the macroporosity development in the range from 200 to 30,000â¯nm. These results suggested that HTC could be an interesting method to obtain soil growing media or green roof materials with adequate hydrophysical properties.
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Estiércol , Pirólisis , Animales , Carbón Orgánico , Suelo , Porcinos , TemperaturaRESUMEN
Endometriosis, defined by the development of endometrial tissue outside the uterus, is a benign disease responsible for infertility and pelvic pain. The diagnosis based on a detailed gynaecological history and a careful clinical examination should be done as early as possible in order to treat patients correctly. Medical treatment is not appropriate in all cases and surgical treatment should be proposed but morbidity is related to the severity of the lesion. Ectopic implantation of endometrial cells needs complex interactions between host tissue and epithelial endometrial cells. The conditions for the development of endometriosis are oestrogeno-dependent growth of endometrial cells, induction of angiogenesis and lymphangiogenesis. Principal cellular and molecular factors of angiogenesis, lymphangiogenesis and fibrosis should be identified in order to develop new therapeutic strategies of endometriosis.
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Endometriosis , Enfermedades del Ovario , Enfermedades Peritoneales , Animales , Modelos Animales de Enfermedad , Endometriosis/complicaciones , Endometriosis/diagnóstico , Endometriosis/tratamiento farmacológico , Endometriosis/etiología , Endometriosis/patología , Endometriosis/cirugía , Femenino , Fibrosis/patología , Humanos , Infertilidad Femenina/etiología , Inflamación/patología , Linfangiogénesis , Ratones , Ratones Desnudos , Neovascularización Patológica , Enfermedades del Ovario/complicaciones , Enfermedades del Ovario/diagnóstico , Enfermedades del Ovario/tratamiento farmacológico , Enfermedades del Ovario/etiología , Enfermedades del Ovario/patología , Enfermedades del Ovario/cirugía , Ovario/patología , Dolor Pélvico/etiología , Enfermedades Peritoneales/complicaciones , Enfermedades Peritoneales/diagnóstico , Enfermedades Peritoneales/tratamiento farmacológico , Enfermedades Peritoneales/etiología , Enfermedades Peritoneales/patología , Enfermedades Peritoneales/cirugía , Peritoneo/patología , Estudios RetrospectivosRESUMEN
Endometriosis, defined by the development of endometrial tissue outside the uterus, is a benign disease responsible for infertility and pelvic pain. The diagnosis based on a detailed gynecological history and a careful clinical examination should be done as early as possible in order to treat patients correctly. Medical treatment is not appropriate in all cases and surgical treatment should be proposed but morbidity is related to the severity of the lesion. Ectopic implantation of endometrial cells needs complex interactions between host tissue and epithelial endometrial cells. The conditions for the development of endometriosis are estrogeno-dependent growth of endometrial cells, induction of angiogenesis and lymphangiogenesis. Principal cellular and molecular factors of angiogenesis, lymphangiogenesis and fibrosis should be identified in order to develop new therapeutic strategies of endometriosis.
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Endometriosis/fisiopatología , Endometriosis/clasificación , Endometriosis/patología , Endometrio/patología , Femenino , Humanos , Infertilidad Femenina/etiología , Inflamación , Neovascularización PatológicaRESUMEN
One of the main objectives of the Spanish Sleep Society is to promote healthy sleep in both the general population and in health professionals. This document aims to conduct a review of the current scientific literature on sleep habits that can serve as the basis on which to establish a set of general recommendations, regarding healthy sleep, for use by the general population in Spain as well as to identify the main challenges faced by research into sleep habits. The document has been developed by a multidisciplinary team made up of members of the Spanish Sleep Society who are experts in paediatric sleep medicine, clinical neurophysiology, pulmonology, neurology, chronobiology, physiology and psychology. The existing scientific literature dealing with sleep habits in the general population was reviewed, and the following aspects were addressed: the current state of sleep habits in the Spanish population; a generic review of the optimum number of hours of sleep; the impact of the environmental setting (noise, temperature, illumination, etc.), hours of sleep, diet and sport, together with several specific sections for children and teenagers, shift-workers and drivers of different vehicles. The conclusions from all the aspects addressed in this document have resulted in a set of final general recommendations that will serve as a guide for the general population and health professionals. Likewise, the principal environmental challenges and future lines of research are also discussed.
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Hábitos , Sueño , Adolescente , Niño , Guías como Asunto , Humanos , EspañaRESUMEN
Since the 90s there increasing interest in early detection of neonatal hearing loss due to the feasibility of universal neonatal screening as well as to the possibility of early intervention. This has led to set up neonatal screening programs based upon otoacoustic emissions and to a great increase in the number of publications in the field. Our hospital started a neonatal hearing loss screening program using otoacoustic emission in March 2000. We used a Capella Cochlear Emissions (MADSEN electronics) equipment. Until May 2003 we have performed the test in 6372 children with a median age of 71 days. In our study, the sensibility of the test was 90.9% and the specificity 99.7%. Our results are similar to those reported in the literature although the age of the children was higher and we have found an incidence of hearing loss lower than other studies.
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Pérdida Auditiva/diagnóstico , Pérdida Auditiva/epidemiología , Tamizaje Neonatal/métodos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Emisiones Otoacústicas Espontáneas/fisiologíaRESUMEN
OBJECTIVE: This study determined the severity of posttraumatic stress and depressive reactions among Nicaraguan adolescents after Hurricane Mitch and the relationship of these reactions to objective and subjective features of hurricane exposure, death of a family member, forced relocation, and thoughts of revenge. METHOD: Six months after the hurricane, 158 adolescents from three differentially exposed cities were evaluated by using a hurricane exposure questionnaire, the Child Posttraumatic Stress Disorder Reaction Index, and the Depression Self-Rating SCALE: RESULTS: Severe levels of posttraumatic stress and depressive reactions were found among adolescents in the two most heavily affected cities. Severity of posttraumatic stress and depressive reactions and features of objective hurricane-related experiences followed a "dose-of-exposure" pattern that was congruent with the rates of death and destruction across cities. Level of impact (city), objective and subjective features, and thoughts of revenge accounted for 68% of the variance in severity of posttraumatic stress reaction. Severity of posttraumatic stress reaction, death of a family member, and sex accounted for 59% of the variance in severity of depression. CONCLUSIONS: After a category 5 hurricane, adolescents in heavily affected areas with extreme objective and subjective hurricane-related traumatic features of exposure experience severe and chronic posttraumatic stress and comorbid depressive reactions. The recovery of the severely affected Nicaraguan adolescents is vital to the social and economic recovery of a country ravaged by years of political violence and poverty. These findings strongly indicate the need to incorporate public mental health approaches, including systematic screening and trauma/grief-focused interventions, within a comprehensive disaster recovery program.
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Trastorno Depresivo/epidemiología , Desastres , Trastornos por Estrés Postraumático/epidemiología , Trastornos de Adaptación/diagnóstico , Trastornos de Adaptación/epidemiología , Trastornos de Adaptación/psicología , Adolescente , Factores de Edad , Comorbilidad , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/psicología , Desastres/estadística & datos numéricos , Femenino , Humanos , Acontecimientos que Cambian la Vida , Masculino , Nicaragua/epidemiología , Probabilidad , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Análisis de Regresión , Índice de Severidad de la Enfermedad , Factores Sexuales , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/psicologíaRESUMEN
Age-associated differences in the response of the initiation and promotion of hepatocellular carcinogenesis in the rat were analyzed. Male Wistar rats 5 and 18 months-old were used throughout. They underwent an experimental design of multistage model of hepatocarcinogenesis: hepatic cells were initiated with the complete carcinogen Aflatoxin B1 (0.5mg/Kg b.w.) and the promotion was performed through a combined treatment of proliferation (partial hepatectomy, 65%) and administration of the tumorigenic promoter phenobarbital (0.1% in drinking water for 21 days). After the treatment, rats were sacrificed and the following parameters were determined: activity and subunit composition of the glutathione S-transferase enzyme system, the number of liver preneoplastic foci and the proliferation cell index. The combined treatment (initiation + promotion) lowered the expression of the mu class GST (rGST M1, rGST M2). The inhibition in rGST M2 in old animals (which in basal conditions had already been lower) was significant. On the other hand, the treatment increased the alpha class GST (rGST A, rGST A3). The number of preneoplastic foci was higher in old rats (number of foci/cm(2): 6.9+/-0.3 vs 3.9+/-0.3 in young rats, p< 0.05). The proliferation cell index did not show age-related differences. Because rGST M2 deficiency coexisted with induced expression of alpha class, the livers would be resistant to some toxic insults, being selectively sensitive to potentially genotoxic substances for which M2 is an essential detoxification pathway. The transition to a rGST M2-deficient phenotype during aging could induce higher responsiveness to genotoxic effects, and might favor the likelihood of further progression, indicating a higher susceptibility of aged animals to the development of carcinogenesis.
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Envejecimiento/metabolismo , Glutatión Transferasa/metabolismo , Neoplasias Hepáticas Experimentales/enzimología , Aflatoxina B1/toxicidad , Animales , Carcinógenos/toxicidad , Glutatión Transferasa/química , Glutatión Transferasa/clasificación , Inmunohistoquímica , Neoplasias Hepáticas Experimentales/etiología , Masculino , Fenobarbital/toxicidad , Lesiones Precancerosas/enzimología , Lesiones Precancerosas/etiología , Antígeno Nuclear de Célula en Proliferación/metabolismo , Subunidades de Proteína , Ratas , Ratas WistarRESUMEN
Hypercalcemia in patients with cancer may reflect the synthesis and secretion into circulation of parathyroid hormone-related protein (PTHrP) produced by the tumor. In the present study, we have measured circulating PTHrP concentrations in healthy subjects and patients using a new immunoradiometric assay (IRMA) that is specific for the 1-86 amino acid sequence of molecule, and in plasma collected with protease inhibitors. Plasma concentrations of PTHrP(1-86) were greater than the detection limit of the assay (0.3 pmol/l) in healthy subjects. All patients with hypercalcemia-associated cancer had PTHrP(1-86) levels significantly greater (median 7.74 pmol/l, P < 0.05) than healthy subjects or patients with cancer and normal serum calcium, primary hyperparathyroidism and hyperparathyroidism secondary to chronic renal failure. Plasma PTHrP and corrected serum calcium were correlated in patients with hypercalcemia-associated cancer. In one patient, a marked decrease in PTHrP and calcium levels was observed following surgery. Our results suggest that this IRMA for PTHrP(1-86) may be useful for diagnosis and monitoring of PTHrP-producing tumors induced hypercalcemia.
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Biomarcadores de Tumor/sangre , Calcio/sangre , Hipercalcemia/sangre , Neoplasias/sangre , Proteínas/metabolismo , Adulto , Biomarcadores/sangre , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Femenino , Estudios de Seguimiento , Humanos , Ensayo Inmunorradiométrico/métodos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Proteína Relacionada con la Hormona Paratiroidea , Fragmentos de Péptidos/análisis , Péptidos/análisis , Inhibidores de Proteasas , Valores de Referencia , Sensibilidad y EspecificidadRESUMEN
The present work analyzes the expression of insulin receptors and theirs related intracellular signaling molecules in partially hepatectomized-diabetic rats. Insulin binding through Scatchard analysis was studied using isolated hepatocytes of Control (Sham-operated), Hepatectomized, Diabetic and Diabetic-Hepatectomized male Wistar rats. In a set of in vivo experiments, the levels of alpha subunit of the insulin receptor, the insulin receptor substrate 1 (IRS-1) and the phosphatidylinositol 3-kinase (PI3K) were determined. [3H]-thymidine incorporation into DNA 24 or 48 h after surgery was assessed in all the experimental groups. Scatchard analysis showed that insulin receptor number was increased in diabetic and in hepatectomized rats in the same extent (64%, with respect to Controls). Diabetic-hepatectomized rats showed a dramatic increase of the receptor concentration (400%) and on the affinity constant (532%). Besides, the insulin receptor expression was increased in the treated groups, being the higher values those of the diabetic-hepatectomized rats. IRS-1 and PI3K showed similar increases. DNA synthesis was not impaired by the diabetes state. In conclusion, increased expression of IR and IRS-1 leads to increased association of PI3K in vivo in diabetic regenerating rats. The enhancement of this pathway may reveal an insulin hyperresponsiveness in these animals.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Hepatectomía , Insulina/farmacología , Regeneración Hepática , Animales , Sitios de Unión , Unión Competitiva , Recuento de Células , Supervivencia Celular , ADN/biosíntesis , Diabetes Mellitus Experimental/metabolismo , Hepatocitos/citología , Hepatocitos/metabolismo , Técnicas In Vitro , Insulina/metabolismo , Proteínas Sustrato del Receptor de Insulina , Masculino , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfoproteínas/metabolismo , Ratas , Ratas Wistar , Receptor de Insulina/metabolismoRESUMEN
PURPOSE: we investigated by immunohistochemistry the pepsinogen C (pepC) expression in uveal melanomas and analyzed the possible relationship to clinicopathological parameters and prognostic significance. METHODS: We studied 22 patients who had undergone enucleation of the eyeball or local tumor resection for uveal melanoma. The specimens were immunostained for pepC on formalin-fixed, paraffin-embedded sections. Sex, age, tumor location, histological type, local invasion, postoperative treatment and metastasis were evaluated. RESULTS: Eleven tumors (50%) were positive for pepsinogen C. The percentage of pepC-positive tumors was significantly higher in uveal melanomas with scleral invasion than in those without scleral invasion (p < 0.01). PepC expression was significantly associated with a shortened overall survival (p < 0.05). CONCLUSIONS: Our results show that pepsinogen C may be expressed by uveal melanoma and suggest that this protein could be considered as a new, unfavorable prognostic factor in these tumors.