Effects of sulglycotide on endogenous prostaglandin synthesis in human antral mucosa

The effect of sulglycotide, a polysulphated glycopeptide isolated from pig duodenum, on PGE2, 6-ketoPGF1 alpha and TxB2 production from isolated biopsy specimens of human antral mucosa was investigated in vitro, in comparison with carbenoxolone. In addition to a tendency toward increased PGE2 production just short of statistical significance, both sulglycotide and carbenoxolone significantly increased 6-ketoPGF1 alpha accumulation in the incubation medium. TxB2 levels were not significantly modified by the two drugs. Therefore, changes in the prostanoid production by human antral mucosa could, at least partially account for the cytoprotective effects of sulglycotide in man.     

Neurological phenotype of Potocki–Lupski syndrome

Potocki–Lupski syndrome is a condition mainly characterized by infantile hypotonia, developmental delay/intellectual disability (DD/ID), and congenital anomalies, caused by duplications of the 17p11.2 region, encompassing RAI1 gene. Its clinical presentation is extremely variable, especially for what concerns the cognitive level and the behavioral phenotype. Such aspects, as well as the dysmorphic/malformative ones, have been covered by previous studies; otherwise neurological features have never been systematically described. In order to delineate the neurological phenotype of Potocki–Lupski Syndrome, we collect an 8‐patients cohort. Developmental milestones are delayed and a mild to moderate cognitive impairment is present in all patients, variably associated with features of autism spectrum disorder, behavioral disturb, and sleep disturb. Hypotonia appears a less frequent finding than what previously reported, while motor clumsiness/coordination impairment is frequent. EGG registration demonstrated a common pattern with excess of diffuse rhythmic activity in sleep phases or while the patient is falling asleep. Brain MRI did not reveal common anomalies, although unspecific white matter changes may be present. We discuss such findings and compare them to literature data, offering an overview on the neurological and cognitive‐behavioral presentation of the syndrome.     

Expression of platelet-derived growth factor and its receptors in normal human liver and during active hepatic fibrogenesis.

Expression of platelet-derived growth factor (PDGF) and its receptor (R) subunits was evaluated in normal human liver and in cirrhotic liver tissue by in situ hybridization and immunohistochemistry. In normal liver, PDGF and PDGF-R subunit expression was limited to a few mesenchymal cells of the portal tract stroma and vessels. In cirrhotic liver, PDGF-A and -B chain mRNA expression was markedly increased and was co-distributed with immunoreactivity for PDGF-AA and -BB in infiltrating inflammatory cells and along vascular structures within fibrous septa. These aspects were paralleled by a marked overexpression of PDGF-R alpha- and beta-subunit mRNAs and of the relative immunoreactivities in a wide range of mesenchymal cells in fibrous septa and in perisinusoidal alpha-smooth-muscle-actin-positive cells. In general expression and distribution of PDGF-R subunits appeared to be related to the activation of different mesenchymal cell types involved in the fibroproliferative process. Therefore, we evaluated the expression of PDGF-R subunits in liver tissue specimens with increasing degrees of necroinflammatory activity. The results of this additional study confirmed that expression of PDGF-R subunits is highly correlated with the severity of histological lesions and collagen deposition. Our results, providing evidence for a functional involvement of PDGF/PDGF-R in liver fibrogenesis, greatly support the results of previous in vitro studies and direct attention toward pharmacological strategies able to affect the series of signaling events arising from the autophosphorylation of PDGF-R subunits.     

Kinetic models for normal and impaired growth

Although microkinetic models are expected to play in the future the same role that macrokinetic models have played in the past, classic mechanistic growth functions are still worthy of study and may still provide insight into auxological problems. The rather rigid shape of macrokinetic models may ignore many interesting fluctuations of growth velocity, but a strong structure allows a robust estimate of growth kinetics even in the case of growth profiles which are largely incomplete, as those derived from current clinical records. In any case, the too simplified shape of these models may be adjusted, to some extent, by adding some unstructured smooth function of residuals which takes into account minor aspects of growth (such as slight spurts during childhood), which cannot be detected in an individual profile because of random errors and inadequate number of observations. This paper recalls the reasons why growth models are useful, analyses briefly the structure and the characteristics of the two fundamental human growth functions, i.e. triple-logistic and PB1, and shows how the use of PB1 model may be extended also to impaired growth, e.g. in girls with Turner syndrome. In this regard, the use of the same model for normal and pathological growth offers the important advantage that differences between growth patterns are not confounded with differences between models.     

Vimentin expression of newly formed rat bile duct epithelial cells in secondary biliary fibrosis

Summary The intermediate filament profile and the growth fraction of hepatocytes and bile duct epithelial cells were studied in a rat model of biliary fibrosis secondary to common bile duct ligation and scission. Strong vimentin expression was observed in epithelial cells of newly formed bile ductules, while normal liver contained only few weakly positive bile duct epithelial cells. All epithelial cells reacted with a pan-cytokeratin antibody. A monoclonal antibody specific for human cytokeratin 7 selectively reacted with both normal and newly formed bile duct epithelial cells. The intermediate filament profile of hepatocytes was constant, showing no changes during proliferation or in periportal areas adjacent to excessive bile duct formations. The proliferation-associated antigen detected by the antibody Ki-67 was present in many hepatocytes, homogeneously distributed in the lobules, but was seen only in a small proportion of the epithelial cells of the newly formed bile ducts. We conclude that vimentin may serve as an indicator for cellular reorganization in the bile duct system, and that the epithelial cells of newly formed bile ductules in this particular model of secondary biliary fibrosis were most likely to be derived from an outgrowth of the biliary duct system and recruitment of preductular epithelial cells. No morphological or immunohistological evidence suggesting a derivation from hepatocytes by ductular metaplasia or from oval cells was obtained.