High glucose induces adipogenic differentiation of muscle-derived stem cells

Regeneration of mesenchymal tissues depends on a resident stem cell population, that in most cases remains elusive in terms of cellular identity and differentiation signals. We here show that primary cell cultures derived from adipose tissue or skeletal muscle differentiate into adipocytes when cultured in high glucose. High glucose induces ROS production and PKCbeta activation. These two events appear crucial steps in this differentiation process that can be directly induced by oxidizing agents and inhibited by PKCbeta siRNA silencing. The differentiated adipocytes, when implanted in vivo, form viable and vascularized adipose tissue. Overall, the data highlight a previously uncharacterized differentiation route triggered by high glucose that drives not only resident stem cells of the adipose tissue but also uncommitted precursors present in muscle cells to form adipose depots. This process may represent a feed-forward cycle between the regional increase in adiposity and insulin resistance that plays a key role in the pathogenesis of diabetes mellitus.     

Chondrosarcomas revisited

Chondrosarcomas are malignant bone tumors with pure hyaline cartilage differentiation; myxoid changes, calcification, or ossification may be present. Several subtypes of chondrosarcomas exist. Behavior patterns vary, ranging from slow-growing nonmetastasizing lesions to aggressive metastasizing sarcomas. Symptoms are usually mild, with duration ranging from several months to years, and usually consist of persistent, dull, aching pain or palpable masses. Radiographic findings include bone expansion with cortical thickening, radiolucent areas with variably distributed punctate or ring-like matrix calcifications, cortical erosion or destruction, endosteal scalloping, and scant or absent periosteal reaction; extension into the soft tissue may be present. Histological differential diagnosis from benign cartilaginous lesions can be achieved by increased cellularity, enlarged plump nuclei, binucleated cells, hyperchromatic nuclear pleomorphism, and permeation of cortical or medullary bone. Atypia is usually mild to moderate; necrosis and mitoses can be seen, particularly in high-grade lesions. Adequate surgery is the mainstay of treatment. High-grade and pelvic chondrosarcomas are best managed with wide resection. Because of the low metastatic potential and low local recurrence rate noted with intralesional surgery, low-grade chondrosarcomas can be treated with curettage (with or without treatment of the defect cavity) with a local adjuvant, such as phenol or cryotherapy. Adjuvant chemotherapy may be considered for mesenchymal and dedifferentiated chondrosarcomas. Radiation therapy can be considered after incomplete resection or if resection is not feasible or would cause unacceptable morbidity.     

Semi-quantification of pneumothorax volume by lung ultrasound

Background

Lung ultrasound (LUS) may accurately diagnose pneumothorax. However, there is uncertainty about its usefulness in the quantification of pneumothorax size. To determine the ability of LUS in the semi-quantification of pneumothorax volume, we compared the projection of the lung point (LP) with the pneumothorax volume measured by computerized tomography (CT) and the interpleural distance on chest radiography (CXR).

Methods

We performed LUS in patients with pneumothorax and all the LP located on the chest wall were compared to CXR and CT studies. The primary outcome of the study was the ability of LP to grade pneumothorax volumes measured by CT. The secondary outcome was the accuracy of LP to predict small and large pneumothorax according to the societal guidelines based on CXR reading.

Results

A total of 124 patients with pneumothorax were enrolled (76 spontaneous, 20 traumatic and 28 post-procedural). Ninety-four CXR and 58 CT were available for the analysis. An LP posterior to the mid axillary line corresponded to three different CXR criteria for large pneumothorax with sensitivity from 81.4 to 88.2 % and specificity from 64.7 to 72.6 %. The mid axillary line also represented the limit for predicting greater than 15 % of lung collapse when volume is measured at CT, with sensitivity 83.3 % and specificity 82.4 %.

Conclusions

LUS-targeted assessment of LP was a useful predictor of pneumothorax volume in this research study setting. LUS reliably classified pneumothorax size when compared to criteria based on CXR reading, particularly the small sized pneumothorax. However, LUS greatly outperformed conventional CXR reading for a graded quantification of the percentage of lung collapse.     

A randomized clinical trial of ultrasound-guided infra-clavicular cannulation of the subclavian vein in cardiac surgical patients: short-axis versus long-axis approach

Purpose

The aim of this study was to compare the success rate and safety of short-axis versus long-axis approaches to ultrasound-guided subclavian vein cannulation.

Methods

A total of 190 patients requiring central venous cannulation following cardiac surgery were randomized to either short-axis or long-axis ultrasound-guided cannulation of the subclavian vein. Each cannulation was performed by anesthesiologists with at least 3 years’ experience of ultrasound-guided central vein cannulation (>150 procedures/year, 50% short-axis and 50% long-axis). Success rate, insertion time, number of needle redirections, number of separate skin or vessel punctures, rate of mechanical complications, catheter misplacements, and incidence of central line-associated bloodstream infection were documented for each procedure.

Results

The subclavian vein was successfully cannulated in all 190 patients. The mean insertion time was significantly shorter (p = 0.040) in the short-axis group (69 ± 74 s) than in the long-axis group (98 ± 103 s). The short-axis group was also associated with a higher overall success rate (96 vs. 78%, p < 0.001), first-puncture success rate (86 vs. 67%, p = 0.003), and first-puncture single-pass success rate (72 vs. 48%, p = 0.002), and with fewer needle redirections (0.39 ± 0.88 vs. 0.88 ± 1.15, p = 0.001), skin punctures (1.12 ± 0.38 vs. 1.28 ± 0.54, p = 0.019), and complications (3 vs. 13%, p = 0.028).

Conclusions

The short-axis procedure for ultrasound-guided subclavian cannulation offers advantages over the long-axis approach in cardiac surgery patients.

     

The cholinergic approach for the treatment of vascular dementia: evidence from pre-clinical and clinical studies

The involvement of an impaired cholinergic neurotransmission in the pathophysiology of cognitive impairment occurring in vascular dementia (VaD), as well as the possibility of treating it by stimulating cholinergic neurotransmission was reviewed. Pre-clinical data suggest that similarly as documented in dementia disorders of neurodegenerative origin, a cholinergic deficit is involved in the pathophysiology of cognitive impairment of vascular origin. In the past, clinical trials have evaluated cholinergic precursors such as lecithin, citicoline and choline alphoscerate. More recent investigations have assessed acetylcholinesterase (AChE) and cholinesterase (ChE) inhibitors such as donepezil, rivastigmine and galantamine. In general, treatment with citicoline, choline alphoscerate, as well as with AChE and ChE inhibitors induced favourable effects on cognitive function in dementia disorders of vascular origin. These positive results should be regarded with caution due to the small number of patients included in controlled clinical trials using cholinergic precursors and to the limited number and sample size of trials with AChE and ChE inhibitors. Among compounds investigated, choline alphoscerate was well tolerated, improved cognitive function in VaD patients to a better extent than citicoline and to similar or better extent than other more recently developed drugs. This particular profile would justify reconsideration of the compound in larger controlled clinical trials for the treatment of cognitive dysfunction associated with dementia disorders of vascular origin.     

Distance optical sensor for quantitative endoscopy

We present a novel optical sensor able to measure the distance between the tip of an endoscopic probe and the anatomical object under examination. In medical endoscopy, knowledge of the real distance from the endoscope to the anatomical wall provides the actual dimensions and areas of the anatomical objects. Currently, endoscopic examination is limited to a direct and qualitative observation of anatomical cavities. The major obstacle to quantitative imaging is the inability to calibrate the acquired images because of the magnification system. However, the possibility of monitoring the actual size of anatomical objects is a powerful tool both in research and in clinical investigation. To solve this problem in a satisfactory way we study and realize an absolute distance sensor based on fiber optic low-coherence interferometry (FOLCI). Until now the sensor has been tested on pig trachea, simulating the real humidity and temperature (37 degrees C) conditions. It showed high sensitivity, providing correct and repeatable distance measurements on biological samples even in case of very low reflected power (down to 2 to 3 nW), with an error lower than 0.1 mm.     

Transforming growth factor-β enhances adhesion of melanoma cells to the endothelium in vitro

Melanoma invasion requires migration through the vascular barrier. An early event in this process is the adhesion of metastatic cells to the endothelium. To elucidate the role of TGF-β in the regulation of this process, human melanoma SK-MEL24 cells were labelled with [5′-³H]-thymidine and co-cultured with bovine pulmonary artery endothelial-cell monolayers. Radioactivity was assumed to be proportional to the number of SK-MEL24 cells bound to the endothelium. A low number of melanoma cells adhered to endothelial cells in a time-related manner. Pretreatment for 24 hr with 0.001 to 10 ng/ml TGF-β₁ or TGF-β₂ of both cell types enhanced melanoma-endothelium adhesion in a dose-dependent manner. Both melanoma and endothelial cells expressed RI- and RII-type TGF-β receptors. The effect of TGF-β was abolished by co-incubation with the proteoglycan decorin. Conditioned media from melanoma-endothelium co-cultures contained latent TGF-β and failed to affect cell-cell adhesion. However, activation of TGF-β by heating the medium or reducing the pH, increased melanoma-endothelium adhesion to an extent similar to that of the TGF-β administered to the cultures. Zimography demonstrated that both cell types expressed urokinase-type plasminogen activator (uPA). Addition of plasminogen to the co-cultures, which was likely to be activated to plasmin by uPA, resulted in activation of TGF-β and parallel stimulation of melanoma-endothelium adhesion. In conclusion, TGF-β may enhance adhesion of melanoma cells to the endothelium, playing a relevant autocrine/paracrine role in the progression of invasive melanoma. Int. J. Cancer 72:1013–1020, 1997. © 1997 Wiley-Liss, Inc.