evidence for acute stimulation of fibrinogen production by glucagon in humans

Fibrinogen, an acute-phase protein, and glucagon, a stress hormone, are often elevated in many conditions of physical and metabolic stress, including uncontrolled diabetes. However, the possible mechanisms for this association are poorly known. We have studied the acute effects of selective hyperglucagonemia (raised from ∼200 to ∼350 pg/ml for 3 h) on fibrinogen fractional secretion rate (FSR) in eight normal subjects during infusion of somatostatin and replacement doses of insulin, glucagon, and growth hormone. Fibrinogen FSR was evaluated by precursor-product relationships using either Phe ( n = 8) or Leu ( n = 2) tracers. Hyperglucagonemia did not change either plasma Phe or Tyr specific activity. After hyperglucagonemia, fibrinogen FSR increased by ∼65% (from 12.9 ± 3.6 to 21.5 ± 6.1% per day, P < 0.025) using plasma Phe specific activity as the precursor pool. FSR increased by ∼80% (from 16.6 ± 4.8 to 29.4 ± 8.8% per day, P < 0.025) if plasma Phe specific activity was corrected for the ketoisocaproate/Leu enrichment (or specific activity) ratio to obtain an approximate estimate of intrahepatic Phe specific activity. FSR increased by ∼60% when using plasma Tyr specific activity as precursor pool ( n = 8) ( P < 0.05), as well as when using the Leu tracer precursorproduct relationship ( n = 2). In conclusion, selective hyperglucagonemia for ∼3 h acutely stimulated fibrinogen FSR using a Phe tracer method. Thus, glucagon may be involved in the increase of fibrinogen concentration and FSR observed under stressed or pathologic conditions

PULSED AND CW LASER TREATMENTS OF IMPLANTED POLYSILICON SOLAR CELLS

Conventional ion implantation and unanalyzed ion bombardment have been used to elaborate the rectifying N+ contact of polycrystalline silicon (Wacker, HEM, CGE) solar cells. Two surface laser annealing in the liquid phase (Nd : YAG laser) and in the solid phase (CO2 laser) regimes have been used. The properties of the solar cells so processed have been investigated. For both doping procedures and both annealing techniques, the cells (conversion) efficiencies under AM1 illumination exceeded 11% for the various polysilicon substrates

A kinematic examination of dual-route processing for action imitation

The dual-route model of imitation suggests that meaningful and meaningless actions are processed through either an indirect or direct route, respectively. Evidence indicates that the direct route is more cognitively demanding, since it relies on mapping visuospatial properties of the observed action on to a performed one. These cognitive demands might negatively influence reaction time and accuracy for actions performed following a meaningless action under time constraints. However, how meaningful and meaningless action imitation processing is reflected in movement kinematics is not yet clear. We wanted to confirm whether meaningless action performance incurs a reaction time cost, whether the cost is reflected in kinematics, and, more generally, to examine kinematic markers of emblematic meaningful and meaningless action imitation. We examined participants’ reaction time and wrist movements when they imitated emblematic meaningful or matched meaningless gestures in either blocks of the same action type, or mixed blocks. Meaningless actions were associated with a greater correction period at the end of the movement, possibly reflecting a strategy designed to ensure accurate completion for less familiar actions under time constraints. Furthermore, in mixed blocks, trials following meaningless actions had a significantly increased reaction time, supporting previous claims that route selection for action imitation may be stimulus-driven. However, there was only convincing evidence for this effect with an interval of ~2948ms, but not ~3573ms or ~2553ms, between movements. Future work motion-tracking the entire hand to assess imitation accuracy, and more closely examining the influence of duration between movements, may help to explain these effects

Anti-tumour necrosis factor-alpha therapy increases body weight in patients with chronic plaque psoriasis: a retrospective cohort study.

Background Chronic plaque psoriasis is associated with overweight or obesity. Anti\u2013tumour necrosis factor- \u3b1 (anti-TNF- \u3b1 ) treatments are now frequently used in psoriasis management. TNF- \u3b1 is deeply involved in body weight homeostasis, which may be affected by TNF- \u3b1 \u2013targeted therapy. Objective To investigate whether anti-TNF- \u3b1 treatments is associated with changes in body weight in patients with chronic plaque psoriasis. Methods We performed a retrospective controlled analysis comparing the variations in body weight and body mass index (BMI) in three closed cohorts of psoriatic patients during a 6-month treatment with etanercept ( N = 58), infliximab ( N = 40) or methotrexate ( N = 43). Results We observed a body weight increment of 1.5 \ub1 2.7 kg (mean \ub1 SD; P = 0.0002) and 2.5 \ub1 3.3 kg ( P = 0.004) in patients treated with etanercept and infliximab, respectively. In contrast, a non-significant change (0.6 \ub1 1.4 kg; P = 0.4) was measured in patients treated with methotrexate. The BMI increased with 0.5 \ub1 0.5 ( P = 0.01) and 0.8 \ub1 1 ( P = 0.003) points in patients treated with etanercept and infliximab, respectively, whereas it did not change (< 0.2 \ub1 0.5; P = 0.06) in patients treated with methotrexate. About one fourth of patients experienced a 4- to 10-kg weight gain. Differences in body weight variations among patients treated with anti-TNF- \u3b1 therapies and methotrexate were statistically significant ( P = 0.0005). We could not identify clinical parameters predicting this phenomenon. Conclusions Patients with psoriasis treated with long-term anti-TNF- \u3b1 therapies may manifest a body weight gain. This effect should be taken into account in the global approach to patients with psoriasis

Rapamycin promotes autophagy cell death of Kaposi’s sarcoma cells through P75NTR activation

The mammalian target of rapamycin inhibitor (mTOR-I) Rapamycin, a drug widely used in kidney transplantation, exerts important anti-cancer effects, particularly in Kaposi's Sarcoma (KS), through several biological interactions. In this in vivo and in vitro study, we explored whether the activation of the autophagic pathway through the low-affinity receptor for nerve growth factor, p75NTR, may have a pivotal role in the anti-cancer effect exerted by Rapamycin in S. Our Kimmunohistochemistry results revealed a significant hyper-activation of the autophagic pathway in KS lesions. In vitro experiments on KS cell lines showed that Rapamycin exposure reduced cell viability by increasing the autophagic process, in the absence of apoptosis, through the transcriptional activation of p75NTR via EGR1. Interestingly, p75NTR gene silencing prevented the increase of the autophagic process and the reduction of cell viability. Moreover, p75NTR activation promoted the upregulation of phosphatase and tensin homolog (PTEN), a tumour suppressor that modulates the PI3K/Akt/mTOR pathway. In conclusion, our in vitro data demonstrated, for the first time, that in Kaposi's sarcoma, autophagy triggered by Rapamycin through p75NTR represented a major mechanism by which mTOR inhibitors may induce tumour regression. Additionally, it suggested that p75NTR protein analysis could be proposed as a new potential biomarker to predict response to Rapamycin in kidney transplant recipients affected by Kaposi's sarcoma

Central venous pressure estimation from ultrasound assessment of the jugular venous pulse

OBJECTIVES: Acquiring central venous pressure (CVP), an important clinical parameter, requires an invasive procedure, which poses risk to patients. The aim of the study was to develop a non-invasive methodology for determining mean-CVP from ultrasound assessment of the jugular venous pulse. METHODS: In thirty-four adult patients (age = 60 ± 12 years; 10 males), CVP was measured using a central venous catheter, with internal jugular vein (IJV) cross-sectional area (CSA) variation along the cardiac beat acquired using ultrasound. The resultant CVP and IJV-CSA signals were synchronized with electrocardiogram (ECG) signals acquired from the patients. Autocorrelation signals were derived from the IJV-CSA signals using algorithms in R (open-source statistical software). The correlation r-values for successive lag intervals were extracted and used to build a linear regression model in which mean-CVP was the response variable and the lagging autocorrelation r-values and mean IJV-CSA, were the predictor variables. The optimum model was identified using the minimum AIC value and validated using 10-fold cross-validation. RESULTS: While the CVP and IJV-CSA signals were poorly correlated (mean r = -0.018, SD = 0.357) due to the IJV-CSA signal lagging behind the CVP signal, their autocorrelation counterparts were highly positively correlated (mean r = 0.725, SD = 0.215). Using the lagging autocorrelation r-values as predictors, mean-CVP was predicted with reasonable accuracy (r2 = 0.612), with a mean-absolute-error of 1.455 cmH2O, which rose to 2.436 cmH2O when cross-validation was performed. CONCLUSIONS: Mean-CVP can be estimated non-invasively by using the lagged autocorrelation r-values of the IJV-CSA signal. This new methodology may have considerable potential as a clinical monitoring and diagnostic tool

Quantitative Metabolomics by 1H-NMR and LC-MS/MS Confirms Altered Metabolic Pathways in Diabetes

Insulin is as a major postprandial hormone with profound effects on carbohydrate, fat, and protein metabolism. In the absence of exogenous insulin, patients with type 1 diabetes exhibit a variety of metabolic abnormalities including hyperglycemia, glycosurea, accelerated ketogenesis, and muscle wasting due to increased proteolysis. We analyzed plasma from type 1 diabetic (T1D) humans during insulin treatment (I+) and acute insulin deprivation (I-) and non-diabetic participants (ND) by 1H nuclear magnetic resonance spectroscopy and liquid chromatography-tandem mass spectrometry. The aim was to determine if this combination of analytical methods could provide information on metabolic pathways known to be altered by insulin deficiency. Multivariate statistics differentiated proton spectra from I- and I+ based on several derived plasma metabolites that were elevated during insulin deprivation (lactate, acetate, allantoin, ketones). Mass spectrometry revealed significant perturbations in levels of plasma amino acids and amino acid metabolites during insulin deprivation. Further analysis of metabolite levels measured by the two analytical techniques indicates several known metabolic pathways that are perturbed in T1D (I-) (protein synthesis and breakdown, gluconeogenesis, ketogenesis, amino acid oxidation, mitochondrial bioenergetics, and oxidative stress). This work demonstrates the promise of combining multiple analytical methods with advanced statistical methods in quantitative metabolomics research, which we have applied to the clinical situation of acute insulin deprivation in T1D to reflect the numerous metabolic pathways known to be affected by insulin deficiency