Preclinical Cushing's syndrome in adrenal incidentalomas

Adrenal tumors are usually diagnosed by clinical symptoms of hormone excess. The increasing use of ultrasound and computed tomography results in the detection of a substantial number of incidentally discovered adrenal tumors. Most of these tumors are nonfunctional adrenocortical adenomas, but a few cases of subclinical cortisol production in "incidentalomas" have been reported. We investigated prospectively the prevalence of autonomous cortisol production in 68 patients (44 females and 24 males, aged 25-90 yr) with adrenal incidentalomas at our institution. As a screening procedure all patients with incidentalomas underwent an overnight dexamethasone suppression test (1 mg). Patients who failed to suppress serum cortisol below 140 nmol/L (5 micrograms/dL) underwent more comprehensive studies (prolonged dexamethasone suppression test, determination of the diurnal rhythm of cortisol secretion in saliva, and CRH stimulation test). Eight patients (12% of all patients with incidentalomas; 5 females and 3 males, aged 25-71 yr) were finally identified as having cortisol- producing tumors, and the findings in these patients were compared with those of overt Cushing's syndrome in 8 patients (8 females, aged 26-50 yr) suffering from cortisol-producing adrenal adenomas. The tumor size of patients with cortisol-producing incidentalomas ranged from 2-5 cm. No specific signs and symptoms of hypercortisolism were present, but arterial hypertension (seven of eight subjects), diffuse obesity (four of eight subjects), and noninsulin-dependent diabetes mellitus (NIDDM; two of eight subjects) were frequently observed. Baseline cortisol levels were in the normal to upper normal range, whereas baseline ACTH levels were suppressed in five of the eight patients. In none of the patients was serum cortisol suppressible by low dose or high dose dexamethasone. The ACTH and cortisol responses to CRH were normal in two, blunted in one, and suppressed in four patients. Unilateral adrenalectomy was performed in seven patients and resulted in temporary adrenal insufficiency in four of them. After surgery, improvement of arterial hypertension, a permanent weight loss in obese subjects, and a better metabolic control of NIDDM were noted in the majority of patients. The following conclusions were reached. Incidentally diagnosed adrenal tumors with pathological cortisol secretion in otherwise clinically asymptomatic patients are more frequently observed than previously assumed. Adrenocortical insufficiency is a major risk in these patients after adrenalectomy. After surgery, hypertension, obesity, and NIDDM may improve. Patients with asymptomatic adrenal incidentalomas, therefore, should be screened for cortisol production by means of an overnight dexamethasone suppression test

Isolation of Human Islets from Partially Pancreatectomized Patients

Investigations into the pathogenesis of type 2 diabetes and islets of Langerhans malfunction 1 have been hampered by the limited availability of type 2 diabetic islets from organ donors2. Here we share our protocol for isolating islets from human pancreatic tissue obtained from type 2 diabetic and non-diabetic patients who have undergone partial pancreatectomy due to different pancreatic diseases (benign or malignant pancreatic tumors, chronic pancreatitis, and common bile duct or duodenal tumors). All patients involved gave their consent to this study, which had also been approved by the local ethics committee. The surgical specimens were immediately delivered to the pathologist who selected soft and healthy appearing pancreatic tissue for islet isolation, retaining the damaged tissue for diagnostic purposes. We found that to isolate more than 1,000 islets, we had to begin with at least 2 g of pancreatic tissue. Also essential to our protocol was to visibly distend the tissue when injecting the enzyme-containing media and subsequently mince it to aid digestion by increasing the surface area

Projective Fourier Duality and Weyl Quantization

The Weyl-Wigner correspondence prescription, which makes large use of Fourier duality, is reexamined from the point of view of Kac algebras, the most general background for noncommutative Fourier analysis allowing for that property. It is shown how the standard Kac structure has to be extended in order to accommodate the physical requirements. An Abelian and a symmetric projective Kac algebras are shown to provide, in close parallel to the standard case, a new dual framework and a well-defined notion of projective Fourier duality for the group of translations on the plane. The Weyl formula arises naturally as an irreducible component of the duality mapping between these projective algebras.Comment: LaTeX 2.09 with NFSS or AMSLaTeX 1.1. 102Kb, 44 pages, no figures. requires subeqnarray.sty, amssymb.sty, amsfonts.sty. Final version with text improvements and crucial typos correction

Transport properties of heterogeneous materials derived from Gaussian random fields: Bounds and Simulation

We investigate the effective conductivity ($\sigma_e$) of a class of amorphous media defined by the level-cut of a Gaussian random field. The three point solid-solid correlation function is derived and utilised in the evaluation of the Beran-Milton bounds. Simulations are used to calculate $\sigma_e$ for a variety of fields and volume fractions at several different conductivity contrasts. Relatively large differences in $\sigma_e$ are observed between the Gaussian media and the identical overlapping sphere model used previously as a `model' amorphous medium. In contrast $\sigma_e$ shows little variability between different Gaussian media.Comment: 15 pages, 14 figure

Fourier Duality as a Quantization Principle

The Weyl-Wigner prescription for quantization on Euclidean phase spaces makes essential use of Fourier duality. The extension of this property to more general phase spaces requires the use of Kac algebras, which provide the necessary background for the implementation of Fourier duality on general locally compact groups. Kac algebras -- and the duality they incorporate -- are consequently examined as candidates for a general quantization framework extending the usual formalism. Using as a test case the simplest non-trivial phase space, the half-plane, it is shown how the structures present in the complete-plane case must be modified. Traces, for example, must be replaced by their noncommutative generalizations - weights - and the correspondence embodied in the Weyl-Wigner formalism is no more complete. Provided the underlying algebraic structure is suitably adapted to each case, Fourier duality is shown to be indeed a very powerful guide to the quantization of general physical systems.Comment: LaTeX 2.09 with NFSS or AMSLaTeX 1.1. 97Kb, 43 pages, no figures. requires subeqnarray.sty, amssymb.sty, amsfonts.sty. Final version with (few) text and (crucial) typos correction

Tumoral response and tumoral phenotypic changes in a rat model of diethylnitrosamine-induced hepatocellular carcinoma after salirasib and sorafenib administration.

Several intracellular signaling pathways that are deregulated during hepatocarcinogenesis might constitute potential targets for hepatocellular carcinoma (HCC) therapy. The aim of this study was to test the potential synergic antitumor effect of salirasib and sorafenib in a diethylnitrosamine (DEN)-induced HCC model in rat. The hypothesis of tumor phenotype changes during treatment was also analyzed. DEN was administered to Wistar rats during 9 weeks to induce cirrhosis and liver cancer. After tumor development, rats were treated with intraperitoneal injections of dimethyl sulfoxide (DMSO), or salirasib, and/or with oral sorafenib 5 days/week, during 4 weeks. At sacrifice, number and size of liver tumors as well as tumor burden were recorded, and all liver tumors were processed for histological and immunohistological analyses. Mortality rate was significantly higher in rats treated with salirasib and/or sorafenib than in the control group ( <i>P</i> =0.001). Tumor burden was smaller in the treated group compared with the DMSO control group ( <i>P</i> =0.044), but a synergistic effect of the two chemotherapies could not be observed. In 62.5% of rats (10/16) treated with salirasib and/or sorafenib, a cytokeratin-7 and -19-positive hepatocholangiocellular carcinoma (HCC/CHC) was found vs 20% (5/25) developing such phenotype in the DMSO control group ( <i>P</i> =0.018). Ki67 immunostaining showed significantly reduced tumor cell proliferation in treated rats ( <i>P</i> =0.001), whereas apoptosis as assessed by caspase-3 activity in cell lysate was similar in all groups. The addition of sorafenib to salirasib did not seem to provide any synergistic therapeutic effect in this study. Both chemotherapeutic agents, administered alone or in combination, induced tumoral phenotypic changes in the majority of rats, a finding not associated with an increased tumor cell proliferation or decreased apoptosis. The rat model described in this work constitutes the first experimental tool generating putatively more aggressive combined HCC/CHC tumors following chemotherapy. Further work is required to better characterize this clinically relevant phenomenon

Modulación de Ras, arresto del ciclo celular e inducción de apoptosis por linalool en células hepáticas tumorales

La vía de mevalonato (VM) produce isoprenoides que son incorporados en productos finales (colesterol, dolicol, ubiquinona) importantes en el crecimiento y proliferación celular. La relación entre la VM y la proliferación de células tumorales son las proteínas preniladas (Ras, Rho, Rac, etc), proteínas de unión a membrana plasmática (MP) que unen GTP y actúan como interruptores moleculares controlando procesos como proliferación, diferenciación y apoptosis.Facultad de Ciencias Médica

Modulación de Ras, arresto del ciclo celular e inducción de apoptosis por linalool en células hepáticas tumorales

La vía de mevalonato (VM) produce isoprenoides que son incorporados en productos finales (colesterol, dolicol, ubiquinona) importantes en el crecimiento y proliferación celular. La relación entre la VM y la proliferación de células tumorales son las proteínas preniladas (Ras, Rho, Rac, etc), proteínas de unión a membrana plasmática (MP) que unen GTP y actúan como interruptores moleculares controlando procesos como proliferación, diferenciación y apoptosis.Facultad de Ciencias Médica

Immunochemical Methods for Ochratoxin A Detection: A Review

The safety of food and feed depends to a great deal on quality control. Numerous compounds and organisms may contaminate food and feed commodities and thus pose a health risk for consumers. The compound of interest in this review is ochratoxin A (OTA), a secondary metabolite of the fungi Aspergillus and Penicillium. Due to its adverse health effects, detection and quantification are of utmost importance. Quality control of food and feed requires extraction and analysis, including TLC, HPLC, MS, and immunochemical methods. Each of these methods has its advantages and disadvantages. However, with regard to costs and rapidity, immunochemical methods have gained much interest in the last decade. In this review an introduction to immunochemistry and assay design will be given to elucidate the principles. Further, the application of the various formats to the detection and quantification of ochratoxin will be described, including the use of commercially available kits