Analysis of characteristics and outcomes by growth hormone treatment duration in adult patients in the Italian cohort of the Hypopituitary Control and Complications Study (HypoCCS).

PURPOSE: To examine differences in effects according to growth hormone (GH) treatment duration in adult GH-deficient patients. METHODS: In the Italian cohort of the observational Hypopituitary Control and Complications Study, GH-treated adults with GH deficiency (GHD) were grouped by duration of treatment; ≤ 2 years (n = 451), > 2 to ≤ 6 years (n = 387) and > 6 years (n = 395). Between-group differences in demographics, medical history, physical characteristics, insulin-like growth factor-I standard deviation score (IGF-I SDS) and lipid profile at baseline, last study visit and changes from baseline to last study visit were assessed overall, for adult- and childhood-onset GHD and by gender using ANOVA for continuous variables and Chi-squared test for categorical variables. RESULTS: At baseline, treatment duration groups did not differ significantly for age, gender, body mass index, GHD onset, IGF-I SDS, lipid profile, and quality of life. Mean initial GH dose did not differ significantly according to treatment duration group in any subgroup, except female patients, with highest mean dose seen in the longest duration group. In the longest duration group for patients overall, adult-onset patients and male patients, there were significant decreases in GH dose from baseline to last visit, and in total and low-density lipoprotein (LDL)-cholesterol concentrations. IGF-I SDS increased, to a greater extent, in the longest duration group for patients overall and female patients. CONCLUSIONS: The results show that long-term GH treatment is associated with decreasing GH dose, increased IGF-I, decreased LDL-cholesterol and the presence of surrogate markers that help to give confidence in a diagnosis of GHD.

CD28 deletion improves obesity-induced liver steatosis but increases adiposity in mice.

BACKGROUND/OBJECTIVES: Lymphocytes have a critical role in visceral adipose tissue (AT) inflammation. The CD28 costimulatory molecule is required for lymphocyte activation and for the development of a functional regulatory T cells (Tregs) compartment; however, its role during obesity is unknown. METHODS: During diet-induced obesity, we investigated the effects of selective interference with CD28 signaling using knockout mice (Cd28KO) and a CTLA4-Ig fusion protein inhibiting CD28-B7 interactions. RESULTS: Cd28 deficiency decreased pathogenic T cells and Treg content within AT without changing the macrophages number. Cd28KO epididymal but not subcutaneous fat was characterized by enlarged adipocytes, reduced levels of inflammatory cytokines and increased Glut4, adiponectin and lipogenic enzyme mRNA levels. This was associated with reduced inflammation, fat accumulation and enhanced glucose metabolism in liver. Weight gain and fasting glucose tolerance were not affected. CTLA4-Ig injections reduced the number of T cells in epididymal AT (epiAT) but not the inflammatory cytokines levels and failed to improve liver fat accumulation. CONCLUSIONS: Deletion of CD28 creates a new pro/anti-inflammatory balance in epiAT and liver and exerts a protective effect against hepatic steatosis.

Poor Nutritional Status Is Associated with Death in a Population of Dialyzed Older Persons.

BACKGROUND: Older patients in hemodialysis have high prevalence of malnutrition that is often associated with rapid weight loss till cachexia. OBJECTIVES: We aimed to investigate whether in older patients undergoing hemodialysis the association between poor nutritional status and mortality may be independent of comorbidities and other risk factors. DESIGN: Retrospective longitudinal study. SETTING: Unit of Nephrology, Dialysis and Kidney Transplantation of the Policlinic Hospital of Milan, Milan, Italy. PARTICIPANTS: A total of 107 prevalent patients undergoing hemodialysis for at least three months. MEASUREMENTS: Sociodemographic, clinical, and biological data were recorded. Unintentional weight loss (UWL) was defined as loss of body weight > 5% in 3 months or > 10% in 6 months. We computed a 21-item Frailty Index that included clinical conditions associated with malnutrition and mortality in this population. Unadjusted and adjusted Cox proportional hazard models were performed to test the association of UWL, albumin and transferrin levels with death. Survival analyses based on Kaplan-Meier estimates were performed. RESULTS: Patients' age was 79 (±7.7) years; 38 (35%) were women. Thirty-one patients (29%) died during follow-up. Eighteen (16.8%) patients experienced UWL during the follow-up period. UWL was positively associated with death in the unadjusted model and even after the progressive inclusion of potential confounders. Low albumin levels were positively associated with death only in the unadjusted and partially adjusted models while low transferrin levels were not associated with death in none of the models. Mortality was significantly higher in those patients experiencing both UWL and albumin levels below 3.5 mg/dL. CONCLUSIONS: In older patients undergoing chronic hemodialysis UWL is associated with mortality independently of comorbidities and other risk factors. Patients presenting both UWL and low albumin levels were those experiencing the worst outcomes in terms of mortality.

The Number of Medications Is Associated with Fractures in a Population of Dialyzed Older Patients with Frailty.

Older persons with chronic kidney disease (CKD) undergoing hemodialysis represent a growing portion of patients characterized by high vulnerability but still marginally studied. This study aimed at exploring the relationship between the number of prescriptions and fractures in older patients with CKD undergoing hemodialysis. A 24-item Frailty Index (FI) based on sociodemographic, clinical and biological data was computed. Unadjusted and adjusted logistic regression models were performed to test the association of prescribed medications with history of fractures. A total of 107 older patients undergoing hemodialysis (38 [35.5%] women, mean age 79.1 standard deviation, SD=7.7) were included in the study. Mean number of prescribed medications was 9.9 (SD=3.9) and was significantly associated with fractures (OR 1.18, 95% CI 1.06-1.32, p=0.003), even after adjustment for potential confounders (OR 1.16, 95% CI 1.03-1.30, p=0.016). If these results will be confirmed, interventions based on deprescribing will become essential in older persons undergoing hemodialysis.

[Epidemiologial profile of invasive candidiasis in intensive care units at a university hospital]. / Perfil epidemiológico de la candidiasis invasora en unidades de pacientes críticos en un hospital universitario.

UNLABELLED: Invasive candidiasis (IC) epidemiology has changed in critically ill patients and limited data are available in Chile. OBJECTIVE: To describe the epidemiological and microbiological profile of IC in critically ill patients. METHODS: Observational prospective study conducted from October 2001 to August 2003 in critically ill adults with suspected or confirmed IC. RESULTS: 53 patients met criteria for IC, finding 18 (33.9%) candidemias, 22 (41.5%) disseminated IC, and 13 (24.5%) local IC. We identified 8 (44.4%) C. albicans and 10 (55.6%) non-albicans Candida in candidemias. C. tropicalis was the predominant non-albicans species (27.7%). An 88.8 % of Candidas sp recovered in candidemias were fluconazole susceptible. Overall hospital mortality was 24.5%. Mortality in candidemia was significantly lower than in disseminated IC (16.6 vs 31.8%, p = 0.02). CONCLUSIONS: A higher proportion of non-albicans Candida was observed in candidemias from critically ill patients. However, most of these strains were fluconazole susceptible. A lower overall mortality was observed in candidemias.

The predictive value of clinical, radiographic, echocardiographic variables and cardiac biomarkers for assessing risk of the onset of heart failure or cardiac death in dogs with preclinical myxomatous mitral valve disease enrolled in the DELAY study.

OBJECTIVES: To identify the predictive value on time to onset of heart failure (HF) or cardiac death of clinical, radiographic, and echocardiographic variables, as well as cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I in dogs with preclinical myxomatous mitral valve disease (MMVD). ANIMALS: One hundred sixty-eight dogs with preclinical MMVD and left atrium to aortic root ratio ≥1.6 (LA:Ao) and normalized left ventricular end-diastolic diameter ≥1.7 were included. METHODS: Prospective, randomized, multicenter, single-blinded, placebo-controlled study. Clinical, radiographic, echocardiographic variables and plasma cardiac biomarkers concentrations were compared at different time points. Using receiving operating curves analysis, best cutoff for selected variables was identified and the risk to develop the study endpoint at six-month intervals was calculated. RESULTS: Left atrial to aortic root ratio >2.1 (hazard ratio [HR] 3.2, 95% confidence interval [95% CI] 1.9-5.6), normalized left ventricular end-diastolic diameter > 1.9 (HR: 6.3; 95% CI: 3.3-11.8), early transmitral peak velocity (E peak) > 1 m/sec (HR: 3.9; 95% CI: 2.3-6.7), and NT-proBNP > 1500 ρmol/L (HR: 5.7; 95% CI: 3.3-9.5) were associated with increased risk of HF or cardiac death. The best fit model to predict the risk to reach the endpoint was represented by the plasma NT-proBNP concentrations adjusted for LA:Ao and E peak. CONCLUSIONS: Logistic and survival models including echocardiographic variables and NT-proBNP can be used to identify dogs with preclinical MMVD at higher risk to develop HF or cardiac death.

Prevalence of growth hormone deficiency in adult polytransfused ß-thalassemia patients and correlation with transfusional and chelation parameters.

BACKGROUND: Dysfunction of GH-IGF-I axis has been described in many patients affected by ß-thalassemia major (TM), especially in children and in adolescents. Recent studies have demonstrated the necessity to evaluate adult patients affected by TM to establish the presence of this alteration which could be relevant in the pathogenesis of cardiac and bone disease, frequently present in this hematological condition. The pathogenesis of this alteration, correlated in the past with iron overload, is not yet completely understood. AIM: The aim of this paper is to evaluate GH-IGF-I axis in a group of adult polytransfused ß-thalassemic patients (TM) and to correlate the results with transfusional and chelation parameters. SUBJECTS AND METHODS: We performed an arginine plus GHRH stimulation test in 28 adult TM patients. Ferritin, IGF-I, liver enzymes, and liver iron concentration, assessed by a superconducting quantum interference device (SQUID) susceptometer were also determined. Moreover, in each patient we evaluated the bone status by a dual-energy X-ray absorptiometry study. RESULTS: We found the presence of GH deficit in 9 patients (32.1%). There were no significant differences between the two groups regarding the value of ferritin, liver enzymes, and liver iron concentration, assessed by SQUID. The group affected by GH deficit showed a worse bone profile. CONCLUSIONS: This study confirms the necessity to screen the status of GH/IGF-I axis in this group of patients, even in adult age. The presence of GH deficiency does not seem to be correlated with the efficacy parameters of transfusional and chelation therapy. Other mechanisms, additional to iron overload, could therefore play a role in the pathogenesis of this clinical condition. The presence of GH deficit seems to be very important on clinical aspects, like bone disease, that are crucial for quality of life in these patients.

Comparison of the performance of a high voltage generator insulated by gas or liquid dielectric.

A module of a wireless high voltage generator was tested immersed in both gaseous and liquid environments providing electrical insulation. The overall performance of the module as well as a detailed performance of the key components are reported, and a comparison between the results in gas and liquid is given. The tests performed on the liquid dielectric show that it is a valid alternative to high pressure gas electrical insulation.

DELay of Appearance of sYmptoms of Canine Degenerative Mitral Valve Disease Treated with Spironolactone and Benazepril: the DELAY Study.

INTRODUCTION: Efficacy of renin-angiotensin-aldosterone system (RAAS) blockade using angiotensin-converting enzyme inhibitors (ACEi) in dogs with preclinical myxomatous mitral valve disease (MMVD) is controversial. HYPOTHESIS: Administration of spironolactone (2-4 mg q 24 h) and benazepril (0.25-0.5 mg q 24 h) in dogs with preclinical MMVD, not receiving any other cardiac medications, delays the onset of heart failure (HF) and cardiac-related death. Moreover, it reduces the progression of the disease as indicated by echocardiographic parameters and level of cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI). ANIMALS: 184 dogs with pre-clinical MMVD and left atrium-to-aortic root ratio (LA:Ao) ≥1.6 and normalized left ventricular end-diastolic diameter (LVEDDn) ≥1.7. METHODS: This is a prospective, randomized, multicenter, single-blinded, placebo-controlled study. Primary outcome variable was time-to-onset of first occurrence of HF or cardiac death. Secondary end points included effect of treatment on progression of the disease based on echocardiographic and radiographic parameters, as well as variations of NT-proBNP and cTnI concentrations. RESULTS: The median time to primary end point was 902 days (95% confidence interval (CI) 682-not available) for the treatment group and 1139 days (95% CI 732-NA) for the control group (p = 0.45). Vertebral heart score (p = 0.05), LA:Ao (p < 0.001), LVEDDn (p < 0.001), trans-mitral E peak velocity (p = 0.011), and NT-proBNP (p = 0.037) were lower at the end of study in the treatment group. CONCLUSIONS: This study failed in demonstrating that combined administration of spironolactone and benazepril delays onset of HF in dogs with preclinical MMVD. However, such treatment induces beneficial effects on cardiac remodeling and these results could be of clinical relevance.

The inflammatory receptor CD40 is expressed on human adipocytes: contribution to crosstalk between lymphocytes and adipocytes.

AIMS/HYPOTHESIS: Obesity is associated with adipose tissue inflammation. The CD40 molecule, TNF receptor superfamily member 5 (CD40)/CD40 ligand (CD40L) pathway plays a role in the onset and maintenance of the inflammatory reaction, but has not been studied in human adipose tissue. Our aim was to examine CD40 expression by human adipocytes and its participation in adipose tissue inflammation. METHODS: CD40 expression was investigated in human whole adipose tissue and during adipocyte differentiation by real-time PCR, Western blot and immunohistochemistry. The CD40/CD40L pathway was studied using recombinant CD40L (rCD40L) in adipocyte culture and neutralising antibodies in lymphocyte/adipocyte co-culture. RESULTS: CD40 mRNA levels in subcutaneous adipose tissue were higher in the adipocyte than in the stromal-vascular fraction. CD40 expression was upregulated during adipocyte differentiation. Addition of rCD40L to adipocytes induced mitogen activated protein kinase (MAPK) activation, stimulated inflammatory adipocytokine production, and decreased insulin-induced glucose transport in parallel with a downregulation of IRS1 and GLUT4 (also known as SCL2A4). rCD40L decreased the expression of lipogenic genes and increased lipolysis. CD40 mRNA levels were significantly higher in subcutaneous adipose tissue than in visceral adipose tissue of obese patients and were positively correlated with BMI, and with IL6 and leptin mRNA levels. Lymphocyte/adipocyte co-culture led to an upregulation of proinflammatory adipocytokines and a downregulation of leptin and adiponectin. Physical separation of the two cell types attenuated these effects, suggesting the involvement of a cell-cell contact. Blocking the CD40/CD40L interaction with neutralising antibodies reduced IL-6 secretion from adipocytes. CONCLUSIONS/INTERPRETATION: Adipocyte CD40 may contribute to obesity-related inflammation and insulin resistance. T lymphocytes regulate adipocytokine production through both the release of soluble factor(s) and heterotypic contact with adipocytes involving CD40.

Aortic dissection in four cats: clinicopathological correlations.

Aortic dissection (AD) is characterized by bleeding within the aortic wall or a tear in the intimal layer of the aortic wall, resulting in the passage of blood from the aortic lumen into the tunica media. In cases of AD, a floating, intimal flap in the aortic lumen divides the lumen into a true portion, with flow present, and a false portion, with no flow. We describe a series of 4 cats with AD of the ascending aorta and moderate aortic insufficiency. Three cats had an acute onset of clinical signs with pericardial effusion and cardiac tamponade, whereas one cat showed a chronic onset without pericardial effusion. Detailed gross and histopathological characterization is available for two cats, which revealed the typical features of AD. One cat also showed connective tissue abnormalities, microscopically resembling Marfan-like syndrome. Concomitant detection of hypertrophic cardiomyopathy in 2 cats represents a novel finding in the veterinary literature. Feline AD is generally associated with systemic hypertension. In all the cats of this case series, blood pressure was normal at presentation, although systemic hypertension before the acute dissection cannot be ruled out. In humans, hypotension is more common with AD of the ascending aorta, so the anatomical location could also play a role in cats. Hypertrophic cardiomyopathy in cats could have been a potential trigger of AD through shear stress. Transthoracic echocardiography, as herein demonstrated, can be considered as a rapid, non-invasive and useful method for the diagnosis of dissection at the level of the ascending aorta.

Survival characteristics and prognostic variables of dogs with mitral regurgitation attributable to myxomatous valve disease.

BACKGROUND: There are few studies evaluating the natural history and prognostic variables in chronic mitral valve disease (CMVI) in a heterogeneous population of dogs. OBJECTIVES: To estimate survival and prognostic value of clinical and echocardiographic variables in dogs with CMVI of varying severity. Five hundred and fifty-eight dogs belonging to 36 breeds were studied. METHODS: Dogs were included after clinical examination and echocardiography. Long-term outcome was assessed by telephone interview with the owner. RESULTS: The mean follow-up time was 22.7 +/- 13.6 months, and the median survival time was 19.5 +/- 13.2 months. In univariate analysis, age>8 years, syncope, HR>140 bpm, dyspnea, arrhythmias, class of heart failure (International Small Animal Cardiac Health Council), furosemide therapy, end-systolic volume-index (ESV-I)>30 mL/m(2), left atrial to aortic root ratio (LA/Ao)>1.7, E wave transmitral peak velocity (Emax)>1.2 m/s, and bilateral mitral valve leaflet engagement were associated with survival time when all causes of death were included. For the cardiac-related deaths, all the previous variables except dyspnea and EDV-I>100 mL/m(2) were significantly associated with survival time. Significant variables in multivariate analysis (all causes of death) were syncope, LA/Ao>1.7 m/s, and Emax>1.2 m/s. For cardiac-related death, the only significant variable was LA/Ao>1.7. CONCLUSIONS AND CLINICAL IMPORTANCE: Mild CMVI is a relatively benign condition in dogs. However, some clinical variables can identify dogs at a higher risk of death; these variables might be useful to identify individuals that need more frequent monitoring or therapeutic intervention.

Chronic plasminogen activator inhibitor-1 (PAI-1) overexpression dampens CD25+ lymphocyte recruitment after lipopolysaccharide endotoxemia in mouse lung.

BACKGROUND: Plasma plasminogen activator inhibitor-1 (PAI-1) level rises during sepsis and confers a worse prognosis. PAI-1 participation to sepsis has been poorly documented and was mainly associated with fibrin deposits. Beside fibrin deposits, increased tissue PAI-1 expression may contribute to the poor outcome of endotoxemia through other mechanisms. OBJECTIVE AND METHODS: During lipopolysaccharide (LPS) challenge, the role of PAI-1 in the early phase of inflammation was examined in the lungs of transgenic mice that either overexpress or lack the PAI-1 gene (PAI-1Tg or PAI-1(-/-)). RESULTS: Analysis of leukocytes revealed that neutrophil and macrophage infiltrations did not differ for PAI-1Tg and wild-type (WT) mice. Remarkably, CD25+ lymphocyte infiltration was totally blunted in PAI-1Tg lungs and inversely correlated with fibrin depositions. In parallel, mRNA levels of the regulatory T cell (Treg) markers FoxP3, CTLA-4, and GITR were significantly lower in PAI-1Tg than in WT lungs after LPS challenge. These data are supported by opposite results in PAI-1(-/-) lungs. The systemic compartments (spleen and peripheral blood) showed no decrease in CD25+, CD4+ CD25+ lymphocytes, and Treg markers in PAI-1Tg mice after LPS injection compared with WT mice. In addition, plasma and lung concentrations of interleukin-6 (IL-6) and macrophage inflammatory protein-1alpha (MIP-1alpha) were significantly higher in PAI-1Tg mice than WT mice. CONCLUSION: Our results suggest that chronic tissue PAI-1 overexpression influences the early phase of the inflammatory response during endotoxemia through the control of T lymphocyte traffic.

Increased metastatic lymph node 64 and CYP17 expression are associated with high stage prostate cancer.

The metastatic lymph node 64 (MLN64), which is localized in the human chromosome 17, encodes a protein with strong homology with steroidogenic acute regulatory protein. Its overexpression in human breast carcinomas and MLNs led to the hypothesis that this protein could be involved in intraneoplastic steroidogenesis. In the present study, we investigated the expression of MLN64 in prostate cancer, another hormone-dependent tumor, and compared its expression with that of CYP17, the gene encoding for the key enzyme of androgen synthesis. We investigated by RT-PCR the expression of MLN64 and CYP17 in 60 prostatic tumors and compared their expression with the stage of disease and the appearance of relapses in a follow-up of 24 months. We found MLN64 and CYP17 expressed in all samples examined, with significantly higher expression in neoplastic tissues with respect to normal tissues (NTs). Moreover, only in neoplastic but not in NTs, a positive linear correlation was found between MLN64 and CYP17 gene expression. MLN64 and CYP17 expression seems to correlate with high stage, high Gleason score and short relapse-free time. These data, for the first time, demonstrate the presence of MLN64 and CYP17 expression in both normal and neoplastic prostatic tissues. The biological role of MLN64 in human prostate and, particularly, in neoplastic tissue is still unclear. Our findings concerning MLN64 and CYP17 gene expression and their significant positive correlation in human prostate cancer may suggest their possible role in intraneoplastic autonomous steroidogenesis.

An analysis of erectile function after intensity modulated radiation therapy for localized prostate carcinoma.

Radiation therapy for prostate cancer can cause erectile dysfunction (ED). Intensity Modulated Radiation Therapy (IMRT) can reduce the amount of radiation to surrounding tissues associated with ED. We characterize the incidence of and factors associated with ED in prostate cancer patients after IMRT at the National Naval Medical Center (NNMC). Patients potent by definition of the Sexual Health Inventory for Men (SHIM) before treatment completed the specific erectile questions of the SHIM after IMRT. Statistical analyses were performed to examine the relationships between several factors and ED. Thirty-two of 45 patients with mean age of 68.2 years (50-86 years) completed the SHIM. The median follow-up was 36.8 months (16-63.6 months) as defined by the time from completion of therapy to reassessment with the SHIM. Eight of 32 patients (25%) had no post-treatment ED (SHIM score 22-25), three of 32 (9%) had mild post-treatment ED (SHIM score 17-21), five of 32 (16%) had mild to moderate ED (SHIM score 12-16), five of 32 (16%) had moderate ED (SHIM score 8-11) and 11 of 32 (34%) had severe post-treatment ED (SHIM score<8). Post-treatment potency was significantly associated with the pre-treatment SHIM score (P=0.001) and history of hypertension (P=0.03). The mean radiation dose to the penile bulb and volume of penile bulb treated were not associated with post-treatment potency (P=0.38, 0.76, respectively). IMRT maintains potency in the majority of patients. This analysis compares favorably in preserving erectile function to previously reported series using conventional external beam radiation therapy techniques. The dose of radiation received by the penile bulb and volume of penile bulb were not associated with post-treatment ED in this analysis.

The STARTRACK experiment.

STARTRACK is the acronym of an experiment that aims to measure ionisation cluster distributions in nanometric sites placed at different distances from an accelerated charged particle track. STARTRACK will first use the 20 nm wall-less detector, already used for studying the nanometric track structure of an alpha particle, and then a new detector designed for measuring ionisation clusters in 10 nm sites. The experiment is mounted on the beam line of the Tandem-Alpi accelerator facility of the Legnaro Laboratories, which supplies ion beams from hydrogen to gold up to energy ranging from 7 to 28 MeV/amu. Track nanodosimetry aims to measure ionisation clusters along and aside the ion track down to occurrence probability of 10(-5). To reach such a goal at least 10(6) events have to be collected and the cluster pile-up probability has to be reduced to less than 10(-6). By using a beam profile detector, which is sensitive to very weak currents, and an event rejector counter, such an aim is feasible.

[Bacillary angiomatosis caused by Bartonella quintana in an human immunodeficiency virus positive patient]. / Angiomatosis bacilar por Bartonella quintana en un paciente con infección por virus de inmunodeficiencia humana.

We report the first case of bacillary angiomatosis due to Bartonella quintana affecting a Chilean a HIV positive patient in Chile. He was a 27 years old, heterosexual male, indigent man known to be HIV positive serological status known from September, 2003, under irregular medical control. On April, 2005, he presented a progressive abscess in the frontal region and erythematous papules in the extremities, that extended to face, thorax and mucoses, becoming nodular and violaceous lesions. Bacillary angiomatosis diagnosis was initially sustained on account of the clinical manifestations, and was confirmed by serology and Warthin Starry staining from a skin biopsy. The etiological agent was identified as Bartonella quintana through universal RPC performed from a cutaneous nodule to detect 16S rRNA gen. Azithromycin plus ciprofloxacin was started, besides of anti retroviral therapy antiretroviral, with the lesions being progressively disappearing.

Experimental setup for the growth of solid crystals of inert gases for particle detection.

Low energy threshold detectors are necessary in many frontier fields of the experimental physics. In this work, we present a novel detection approach based on pure or doped matrices of inert gases solidified at cryogenic temperatures. The small energy release of the incident particle can be transferred directly (in pure crystals) or through a laser-driven ionization (in doped materials) to the electrons of the medium that are then converted into free electrons. The charge collection process of the electrons that consists in their drift within the crystal and their extraction through the solid-vacuum interface gives rise to an electric signal that we exploit for preliminary tests of charge collection and crystal quality. Such tests are carried out in different matrices of neon and methane using an UV-assisted apparatus for electron injection in crystals.

Expression of adrenomedullin in adipose tissue of lean and obese women.

OBJECTIVE: Adrenomedullin (AM), a potent vasodilatator and antioxidative peptide, was shown recently to be expressed by adipose tissue. The aim of our study was to investigate the precise localization of AM within human adipose tissue, and to examine AM regulation in obesity. DESIGN: Subcutaneous (SC) and omental (OM) adipose tissues from 9 lean and 13 obese women were profiled for AM expression changes. Preadipocytes from human adipose tissue were isolated and differentiated under defined adipogenic conditions. METHODS: AM expression was analyzed by immunohistochemistry, in situ hybridization and quantitative RT-PCR. RESULTS: A strong AM expression was observed in vessel walls, stromal cell clusters and isolated stromal cells, some of them being CD 68 positive, whereas mature adipocytes were not labeled. Calcitonin receptor-like receptor and receptor activity-modifying proteins (RAMP) 2 and RAMP 3 were expressed in vessel walls. In vitro, preadipocytes of early differentiation stages spontaneously secreted AM. No difference in AM localization was found between SC and OM adipose tissue. AM levels in SC tissue did not differ between lean and obese subjects. By contrast, AM levels in OM tissue were significantly higher in obese as compared with lean women. Moreover, we found a positive relationship between OM AM and tumor necrosis factor alpha mRNA levels and AM-immunoreactive area in OM tissue followed the features of the metabolic syndrome. CONCLUSION: Stromal cells from human adipose tissue, including macrophages, produce AM. Its synthesis increased in the OM territory during obesity and paralleled the features of the metabolic syndrome. Therefore, AM should be considered as a new member of the adipokine family.