The discovery of the lymphatic system in the seventeenth century. Part II: the discovery of Chyle vessels

In the seventeenth century, opportunities to discover chyle came about through the revival of vivisection. Gaspare Aselli discovered chyle vessels in a living well-fed dog in 1622. He introduced the term 'lacteals' or milky veins. According to Aselli, the lacteals passed through a mesenteric gland which he called 'pancreas'. The 1627 edition of Aselli's booklet was the start of a 'lymphomania', which led to the dissection and vivisection of hundreds of animals, with the University of Leiden being the clear leader in this field. The prominent researchers in Leiden were Jacobus Sylvius and Johannes Walaeus, who performed diverse experiments to support Harvey's theories on systemic circulation, and to find out the correct anatomy and physiology of lacteals and mesenteric glands. Another centre of excellence was Padua, where Veslingius and Wirsüng introduced the idea of the prominent role of the 'real pancreas', and its duct in the transformation of digested food into clear chyle. The idea of the transport of chyle to the liver was an additional support for Galen's theories regarding the function of the liver. Nevertheless, as time went on, there were fewer and fewer believers in Galenic doctrine.     

A new tool to test active ingredient using lactic acid in vitro,a help to understand cellular mechanism involved in stinging test: An example using a bacterial polysaccharide (Fucogel®)

The stinging test is an in vivo protocol that evaluates sensitive skin using lactic acid (LA). A soothing sensation of cosmetics or ingredients can be also appreciated through a decrease in stinging score. To predict the soothing sensation of a product before in vivo testing, we developed a model based on an LA test and substance P (SP) release using a co‐culture of human keratinocytes and NGF‐differentiated PC12 cells. A bacterial fucose‐rich polysaccharide present in Fucogel^® was evaluated as the soothing molecule in the in vivo stinging test and our in vitro model. Excluding toxic concentrations, the release of SP was significant from 0.2% of lactic acid for the PC12 cells and from 0.1% of lactic acid for the keratinocytes. When the pH was adjusted to approximately 7.4, LA did not provoke SP release. At these concentrations of LA, 0.1% of polysaccharide showed a significant decrease in SP release from the two cellular types and in co‐cultures without modifying the pH of the medium. In vivo, a stinging test using the polysaccharide showed a 30% decrease in prickling intensity vs the placebo in 19 women between the ages of 21 and 69. Our in vitro model is ethically interesting and is adapted for cosmetic ingredients screening because it does not use animal experimentation and limits human volunteers. Moreover, Fucogel^® reduced prickling sensation as revealed by the in vivo stinging test and inhibits the neurogenic inflammation as showed by our new in vitro stinging test based on SP release.     

MR imaging features of focal liver lesions in Wilson disease

Hepatic involvement in Wilson disease (WD) manifests as a diffuse chronic disease in the majority of patients. However, in a subset of patients focal liver lesions may develop, presenting with a wide range of imaging features. The majority of focal liver lesions in patients with WD are benign nodules, but there are reports that have described malignant liver tumors or dysplastic nodules in these patients. Because of the possibility of malignant transformation of liver nodules, major concerns have been raised with respect to the management and follow-up of patients with WD in whom focal liver lesions have been identified. The assessment of liver involvement in patients with WD is generally performed with ultrasonography. However, ultrasonography conveys limited specificity so that magnetic resonance (MR) imaging is often performed to improve lesion characterization. This review was performed to illustrate the spectrum of MR imaging features of focal liver lesions that develop in patients with WD. It is assumed that familiarity with the MR imaging presentation of focal liver lesions in WD may help clarify the actual nature of hepatic nodules in patients with this condition.     

Therapeutic approaches for neuronopathic lysosomal storage disorders

Therapy of the central nervous system (CNS) manifestations of lysosomal storage diseases (LSDs) has remained a major challenge because of its inability to deliver therapeutic agents efficiently across the intact blood–brain barrier. Non-specific therapies such as hematopoietic stem cell transplantation have been useful in globoid cell leukodystrophy (Krabbe disease) and in some mucopolysaccharidoses. Anti-inflammatory agents also show promise as adjuvant therapy. High doses of replacement therapy with native or modified enzyme show renewed promise for correction of CNS cells. Alternatively, small molecules can enter the brain relatively easily and promote reduction of accumulated substrate or function as pharmacological chaperones to enhance the level of the deficient enzyme. Gene therapy is still being developed and tested in patients. It is therefore likely that, thanks to a better understanding of disease mechanism, a variety of therapeutic approaches, used alone or in combination, will be useful to treat the devastating neurological complications of LSDs.     

Sphincter pharyngoplasty as a treatment of velopharyngeal incompetence in young people: a prospective evaluation of effects on sleep structure and sleep respiratory disturbances

BACKGROUND: Sphincter pharyngoplasty (SP) appears to be the more "physiologic" surgical technique to treat velopharyngeal incompetence (VPI). This procedure creates a dynamic sphincter of variable diameter and keeps the flexibility of the soft palate. SP also induces velopharyngeal size reduction, mainly in the transverse diameter, which may cause upper airway (UA) occlusions during sleep. AIM: To prospectively evaluate the effects of SP by a modified Orticochea procedure on sleep structure and sleep respiratory disturbances. METHODS: Polysomnographic studies before and after surgery in 17 consecutive patients treated by a modified Orticochea procedure SP for VPI. RESULTS: For the whole group, SP did not induce significant impairment of apnea-hypopnea index or nocturnal oxygen saturation. Slow-wave sleep (SWS) was significantly reduced after surgery (25 +/- 9% of total sleep time [TST] vs 28 +/- 9% of TST before SP [p = 0.04]). Following surgery, there was a trend for an increase in the microarousal index) (p = 0.09) and more specifically in respiratory-related microarousals. CONCLUSION: SP, although creating a clinically obvious reduction of velopharyngeal diameter, generally did not lead to the occurrence of an obstructive sleep apnea syndrome. However, we found a significant reduction of SWS quantity and a trend toward an increase in the number of cortical microarousals. These findings suggest that the reduction of UA diameter associated with the surgical technique leads to increases in respiratory effort sufficient to induce sleep fragmentation and SWS reduction, even in the absence of apneas or hypopneas.     

Treatment with atorvastatin ameliorates hepatic very-low-density lipoprotein overproduction in an animal model of insulin resistance, the fructose-fed Syrian golden hamster: evidence that reduced hypertriglyceridemia is accompanied by improved hepatic insulin sensitivity

A novel animal model of insulin resistance, the fructose-fed Syrian golden hamster has been previously documented to exhibit considerable hepatic very-low-density lipoprotein (VLDL) overproduction concomitant with the development of whole body insulin resistance. Here, we investigated whether hepatic lipoprotein overproduction can be ameliorated by treatment with a hydroxymethyl glutaryl conenzyme A (HMG-CoA) reductase inhibitor, atorvastatin, using a series of ex vivo experiments. Hamsters were fed a fructose-enriched diet for 14 days to induce a state of insulin resistance, and then continued on a fructose-enriched diet supplemented with or without 40 mg/kg atorvastatin per day for 14 days. Fructose feeding in the first 2 weeks caused a significant increase in plasma total cholesterol and triglyceride levels. There was a significant decline in plasma triglyceride levels following supplementation with the inhibitor (50% to 59%; P <.05). Experiments with primary hepatocytes revealed a decreased VLDL-apolipoprotein B (apoB) production (37.4% +/- 10.4%; P <.05) in hamsters treated with atorvastatin. Interestingly, atorvastatin treatment partially attenuated (by 23%) the elevated hepatic level of microsomal triglyceride transfer protein (MTP) induced by fructose feeding. There was molecular evidence of improved hepatic insulin sensitivity with atorvastatin treatment based on assessment of the phosphorylation status of the insulin receptor and the expression of protein tyrosine phosphatase-1B. The improvement in insulin signaling was not mediated by a change in hepatic triglyceride accumulation as no significant difference was observed in liver triglyceride levels. Taken together, these data suggest that statins can ameliorate the VLDL-apoB overproduction state observed in a fructose-fed, insulin-resistant hamster model, and may potentially contribute to an enhanced hepatic insulin sensitivity.