The link between molecules produced by the adipose tissue, obesity and atherothrombosis

Obesity is associated with increased risk of cardiovascular morbidity. Biologically active molecules produced by adipose tissue constitute a critical link between obesity and cardiovascular complications. Adipose tissue has recently been recognized to be an important endocrine organ that controls energy metabolism. It also secretes adipocytokines, which can modify vascular responses, and antifibrinolytics, including plasminogen activator inhibitor 1, which favors fibrin accumulation, and proinflammatory cytokines, which facilitate the inflammatory response. Here we review new advances in our understanding of the mechanisms linking the endocrine activity of adipose tissue to vascular risk.     

Dietary fiber intake and risk factors for cardiovascular disease in French adults

BACKGROUND: Increased consumption of dietary fiber is widely recommended to maintain or improve health, but knowledge of the relation between dietary fiber sources and cardiovascular disease risk factors is limited. OBJECTIVE: We examined the relation between the source or type of dietary fiber intake and cardiovascular disease risk factors in a cohort of adult men and women. DESIGN: In a cross-sectional study, quintiles of fiber intake were determined from dietary records, separately for 2532 men and 3429 women. Age- and multivariate-controlled logistic models investigated the odds ratios of abnormal markers for quintiles 2-5 of fiber intake compared with the lowest quintile. RESULTS: The highest total dietary fiber and nonsoluble dietary fiber intakes were associated with a significantly (P < 0.05) lower risk of overweight and elevated waist-to-hip ratio, blood pressure, plasma apolipoprotein (apo) B, apo B:apo A-I, cholesterol, triacylglycerols, and homocysteine. Soluble dietary fiber was less effective. Fiber from cereals was associated with a lower body mass index, blood pressure, and homocysteine concentration; fiber from vegetables with a lower blood pressure and homocysteine concentration; and fiber from fruit with a lower waist-to-hip ratio and blood pressure. Fiber from dried fruit or nuts and seeds was associated with a lower body mass index, waist-to-hip ratio, and fasting apo B and glucose concentrations. Fiber from pulses had no specific effect. CONCLUSION: Dietary fiber intake is inversely correlated with several cardiovascular disease risk factors in both sexes, which supports its protective role against cardiovascular disease and recommendations for its increased consumption.     

Soft tissue absorption tomography with correction for scattering aberrations

Among the many factors involved in ultrasound attenuation phenomena, scattering effects play a major role, even in the unexpected case of soft tissues. It is proposed in this study to quantitatively evaluate the scattering affecting the measurements before reconstructing the absorption parameter alone. The reconstruction procedure involves three steps: (1) Estimating the sound speed map using a transmission tomography algorithm. This estimation procedure provides a numerical phantom of the organ probed, cleared of all dissipative components. This absorption free phantom mimics the (viscoacoustic) tissues imaged except for the density and absorption characteristics: the density a priori equals 1000 kg/m3 and the absorption is not taken into account. The impedance fluctuations in the object are therefore approximated on the basis of the sound speed contrast. (2) Synthesing the field scattered by the absorption free phantom; the attenuation observed here results solely from the scattering phenomenon. The synthesis is carried out using a finite-element time domain code simulating the ultrasonic propagation through the phantom. It provides the scattering distortion reference introduced into the log spectral absorption estimator. (3) Reducing the scattering distortions affecting the integrated absorption measured along the ray paths using a log spectral procedure. The corrected integrated absorption is then processed using a tomographic reconstruction procedure that provides an estimate of the absorption distribution. Simple numerical simulations show the improvement obtained in the absorption estimates with this approach.     

Rapid up-regulation of the neuronal serotoninergic phenotype by brain-derived neurotrophic factor and cyclic adenosine monophosphate: relations with raphe astrocytes

Up-regulation of the neuronal serotoninergic phenotype in relation to astrocytic population was studied in primary cultures of rat embryonic rostral raphe. Short treatments (18 hr at day in vitro 4) with brain-derived neurotrophic factor (BDNF) or dibutyryl-cAMP (dBcAMP) increased the number of serotoninergic neurons by approximately 80% and approximately 40%, respectively, and markedly enhanced the branching (by 11-fold and 5-fold, respectively) and total length (by 4-fold and 2.5-fold, respectively) of their neurites. Concomitantly, under BDNF treatment, the astrocyte population was decreased by half and became mostly protoplasmic-like. In contrast, dBcAMP treatment also reduced the astrocytic cell density (by one-third) but induced a stellate morphology. Similar short treatment with the astrocyte-derived S100beta factor induced no modification of the serotonin (5-HT) neuronal phenotype nor of astrocytes morphology. Both BDNF- and cAMP-induced effects were abolished by simultaneous treatment with the specific tyrosine kinase inhibitor genistein, suggesting a role for the high-affinity BDNF receptor tyrosine kinase (TrkB). These data suggest that BDNF and cAMP, but not S100beta, rapidly induce both an up-regulation of the 5-HT neuronal phenotype and modifications of the neighboring astrocytes in a TrkB-dependent manner.     

Sternal resection and reconstruction for primary malignant tumors

BACKGROUND: Primary malignant sternal tumors (PMST) are locally aggressive and their optimal surgical management still continues to evolve. METHODS: From 1986 to 2002, 38 patients (25 females/13 males) underwent radical resection of PMST. This series included 33 sarcomas, 17 of which had been radiation-induced, 3 hematologic tumors, and 2 carcinomas. Seventeen were high-grade tumors. Nine patients had received preoperative chemotherapy. Twelve patients required extensive skin excision. Eight total, seven subtotal, and 23 partial sternectomies were performed. Resection was extended to the anterior chest-wall in 4 patients, lung in 4, brachiocephalic vein in 3, superior vena cava in 2, and pericardium in 1. In 36 patients, chest wall stability was obtained by Marlex (n = 21) or Vicryl (n = 2) mesh and polytetrafluoroethylene patch (n = 13), with methylmethacrylate reinforcement in 12 patients. Soft tissue coverage was done by the pectoralis major muscles with skin advancement in 25 patients, a myocutaneous flap in 11, a breast transposition in 1, and a skin flap in 1. Omentoplasty was performed in 3 patients. RESULTS: One patient died from pneumonia. Two patients needed a tracheostomy after total sternectomy. No flap-related complication was observed. Four local septic complications required removal of the composite prosthesis with reoperations. Local recurrence occurred in 9 patients, 7 patients having a repeat resection. Metastases developed in eight. The 5-year overall and disease-free survival was 66% and 53%, respectively. The histologic grade of sarcomas was a survival predictor (high grade versus others p = 0.035). CONCLUSIONS: Wide resection of PMST is necessary to minimize local recurrence. Large sternal defects are safely reconstructed with a musculocutaneous flap. We suggest that the use of methylmethacrylate should be limited to reconstruction after total sternectomy.     

Gender differences in non-small-cell lung cancer survival: an analysis of 4,618 patients diagnosed between 1997 and 2002

Background

Gender has been reported as a predictor for nonsmall cell lung cancer (NSCLC) survival. Most of the reports are limited to selected groups of patients. The magnitude of gender effect on NSCLC survival across disease stage, tumor histology, and therapies needs to be further characterized.

Methods

A cohort of 4,618 patients diagnosed with NSCLC was prospectively enrolled and actively followed. Vital status of each patient was verified through multiple complementary sources. Cox proportional hazards models were developed to compare postdiagnosis survival between genders adjusting for age at diagnosis, tumor histology and grade, stage, pack-years smoked, and treatment received (resection, radiation, or chemotherapy).

Results

There were 2,724 men (59%) and 1,894 women (41%), with a median age at diagnosis of 68 years in men and 66 in women (p < 0.01). More men smoked and were heavier smokers than women. Adenocarcinoma was the most frequent histology in both genders. No difference was found in stage and treatment between genders. The estimated survival in men was 51% (95% CI: 49%, 53%) and 15% (95% CI: 12%, 17%) at one and five years, respectively, and in women was 60% (95% CI: 58%, 62%) and 19% (95% CI: 16%, 22%). Men were at a significantly increased risk of mortality compared to women following a diagnosis of NSCLC (adjusted relative risk: 1.20, 95% CI: 1.11, 1.30), particularly for patients with stage III/IV disease or adenocarcinoma.

Conclusions

Male gender is confirmed to be an independent unfavorable prognostic indicator for NSCLC survival.     

A fission yeast strain expressing human CDC25A phosphatase: a tool for selectivity studies of pharmacological inhibitors of CDC25

Fission yeast is a simple eukaryotic model organism in which many aspects of cell cycle control can be explored. We examined by homologous recombination whether the human CDC25A phosphatase could substitute for the function of the fission yeast Cdc25. We first show: (a) that CDC25A efficiently replaces the endogenous Cdc25 mitotic inducer for vegetative growth and (b) that CDC25A is able to partially restore a functional checkpoint in response to both ionising and UV irradiation, but not a DNA replication checkpoint. We then describe a simple assay in which we demonstrate that growth of the humanised CDC25A strain is strongly repressed in a CDC25-dependent manner by BN2003, a potent chemical inhibitor of CDC25 belonging to the benzothiazoledione family. The ease of manipulation of fission yeast humanised CDC25 cells and the simplicity of the above assay offer a powerful tool with which to investigate the specificity of pharmacological inhibitors of CDC25.Communicated by M. Yamamoto