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P Debbage

Publications and source records attributed to P Debbage.

10 recordsLinked to original sources
PubMed2006

Comparative in vivo mucoadhesion studies of thiomer formulations using magnetic resonance imaging and fluorescence detection.

The aim of this study was to compare different oral delivery systems based on the thiolated polymer polycarbophil-cysteine (PCP-Cys) and to provide evidence for the validity of the hypothesis that unhydrated polymers provide better mucoadhesion in vivo. To achieve dry polymer application, a new, experimental dosage form named Eutex (made of Eudragit L100-55 and latex) capsule has been developed. Magnetic resonance imaging was used to localize the point of release of the thiolated polymer from the application forms via the positive magnetic resonance signal from a gadolinium complex (Gd-DTPA). In vivo mucoadhesion was determined by ascertaining the residence time of the fluorescence-tagged thiomer on intestinal mucosa after 3 h. Results showed that in comparison to conventional application forms the Eutex capsules led to 1.9-fold higher mucoadhesive properties of PCP-Cys when compared to application with a conventional enteric-coated capsule, and to 1.4-fold higher mucoadhesion when compared to administration with an enteric-coated tablet of the thiomer. The findings of this study should contribute to the understanding of mucoadhesion and mucoadhesion influencing parameters in vivo and should therefore be of considerable interest for the development of future mucoadhesive oral drug delivery dosage forms.

Animals↗
PubMed2005

Human triglyceride-rich lipoproteins impair glucose metabolism and insulin signalling in L6 skeletal muscle cells independently of non-esterified fatty acid levels.

AIMS/HYPOTHESIS: Elevated fasting and postprandial plasma levels of triglyceride-rich lipoproteins (TGRLs), i.e. VLDL/remnants and chylomicrons/remnants, are a characteristic feature of insulin resistance and are considered a consequence of this state. The aim of this study was to investigate whether intact TGRL particles are capable of inducing insulin resistance. METHODS: We studied the effect of highly purified TGRLs on glycogen synthesis, glycogen synthase activity, glucose uptake, insulin signalling and intramyocellular lipid (IMCL) content using fully differentiated L6 skeletal muscle cells. RESULTS: Incubation with TGRLs diminished insulin-stimulated glycogen synthesis, glycogen synthase activity, glucose uptake and insulin-stimulated phosphorylation of Akt and glycogen synthase kinase 3. Insulin-stimulated tyrosine phosphorylation of IRS-1, and IRS-1- and IRS-2-associated phosphatidylinositol 3-kinase (PI3K) activity were not impaired by TGRLs, suggesting that these steps were not involved in the lipoprotein-induced effects on glucose metabolism. The overall observed effects were time- and dose-dependent and paralleled IMCL accumulation. NEFA concentration in the incubation media did not increase in the presence of TGRLs indicating that the effects observed were solely due to intact lipoprotein particles. Moreover, co-incubation of TGRLs with orlistat, a potent active-site inhibitor of various lipases, did not alter TGRL-induced effects, whereas co-incubation with receptor-associated protein (RAP), which inhibits interaction of TGRL particles with members of the LDL receptor family, reversed the TGRL-induced effects on glycogen synthesis and insulin signalling. CONCLUSIONS/INTERPRETATION: Our data suggest that the accumulation of TGRLs in the blood stream of insulin-resistant patients may not only be a consequence of insulin resistance but could also be a cause for it.

Animals↗
PubMed2001

Ossification in the human calcaneus: a model for spatial bone development and ossification.

Perichondral bone, the circumferential grooves of Ranvier and cartilage canals are features of endochondral bone development. Cartilage canals containing connective tissue and blood vessels are found in the epiphysis of long bones and in cartilaginous anlagen of small and irregular bones. The pattern of cartilage canals seems to be integral to bone development and ossification. The canals may be concerned with the nourishment of large masses of cartilage, but neither their role in the formation of ossification centres nor their interaction with the circumferential grooves of Ranvier has been established. The relationships between cartilage canals, perichondral bone and the ossification centre were studied in the calcaneus of 9 to 38-wk-old human fetuses, by use of epoxy resin embedding, three-dimensional computer reconstructions and immunhistochemistry on paraffin sections. We found that cartilage canals are regularly arranged in shells surrounding the ossification centre. Whereas most of the shell canals might be involved in the nourishment of the cartilage, the inner shell is directly connected with the perichondral ossification groove of Ranvier and with large vessels from outside. In this way the inner shell canal imports extracellular matrix, cells and vessels into the cartilage. With the so-called communicating canals it is also connected to the endochondral ossification centre to which it delivers extracellular matrix, cells and vessels. The communicating canals can be considered as inverted 'internal' ossification grooves. They seem to be responsible for both build up intramembranous osteoid and for the direction of growth and thereby for orientation of the ossication centre.

Calcaneus↗
PubMed2000

Monitoring of tumor microcirculation during fractionated radiation therapy in patients with rectal carcinoma: preliminary results and implications for therapy.

PURPOSE: To measure microcirculatory changes during chemoirradiation and to correlate perfusion index (PI) values with therapy outcome. MATERIALS AND METHODS: Perfusion data in 11 patients with cT3 (clinical staging, tumor invaded the perirectal tissue) rectal carcinoma who underwent preoperative chemoirradiation were analyzed. Perfusion data were acquired by using a T1 mapping sequence with a whole-body magnetic resonance (MR) imager. After contrast medium was intravenously infused at a constant rate, concentration-and-time curves were evaluated for arterial blood and tumor. All patients underwent MR imaging before and at constant intervals during chemoirradiation. Clinical stages before therapy were compared with surgical stages after therapy. RESULTS: Spatial and temporal resolution on dynamic T1 maps were sufficient to reveal changes in contrast medium accumulation in the tumor. Comparison of PI values and radiation dose showed a significant increase in the 1st (P: =.003) and 2nd weeks (P: =.01) of treatment; values subsequently returned to pretreatment levels or showed a renewed increase. High initial PI values correlated with greater lymph node downstaging (P: =.042). CONCLUSION: Dynamic T1 mapping provides a suitable tool for monitoring tumor microcirculation during chemoirradiation and offers the potential for individual optimization of therapeutic procedures. Furthermore, these results indicate that the PI map may serve as a prognostic factor.

Adenocarcinoma↗
PubMed1999

[Development and application of dynamic MR imaging in the evaluation of perfusion changes in rectal carcinoma during radiotherapy in clinical routine. Preliminary results].

PURPOSE: This study was aimed at measuring microcirculatory parameters and contrast medium accumulation within the rectal carcinoma during fractionated radiotherapy in the clinical setting. MATERIAL AND METHODS: Perfusion data were observed in patients with rectal carcinoma (n = 8) who underwent a pre-operative combined chemo/radiotherapy. To acquire perfusion data, an ultrafast T1 mapping sequence was carried out on a 1.5-Tesla whole body imager to obtain T1 maps at intervals of 14 or 120 seconds. The overall measurement time was 40 minutes. The transaxial slice thickness (5 mm) was chosen in such a way that both arterial vessels and the tumor could be clearly identified. The gadolinium-DTPA (Gd-DTPA) concentration time curve was evaluated for arterial blood and tumor after intravenous constant rate infusion. The method allows a spatial resolution of 2 x 2 x 5 mm and a temporal resolution of 14 seconds. Patients underwent MR imaging before and at constant intervals during fractionated radiotherapy. RESULTS: Spatial and temporal resolution of dynamic T1 mapping was sufficient to reveal varying CM accumulation levels within the tumor and to identify the great arteries in the pelvis. In 6 patients Gd-DTPA concentration-time-curves were evaluated within the tumor during radiation. Pi index of Gd-DTPA versus radiation dose showed a significant increase in the first or second week of treatment, then either returned slowly to pretreatment level or a renewed increase was observed. The average Pi-value at the beginning was 0.16 (+/- 0.049), reaching highest level of 0.23 (+/- 0.058). In all groups the rise from the Pi-value to the Pi-maximum was statistically significant. The relative increase in perfusion ranged between 20 to 83%. CONCLUSION: The results show, that the ultrafast MR-technique described above provide a suitable tool for monitoring tumor microcirculation during therapeutic interventions and offers the potential for an individualized optimization of therapeutic procedures.

Aged↗
PubMed1993

Immunological cross-reactivities between proteins secreted by the subcommissural organ, and plant lectins.

The glial subcommissural organ (SCO) discharges a glycoprotein-rich secretory product into the third ventricle to form Reissner's fibre (RF). The SCO proteins bear N-linked oligosaccharides, such as mediate many cell-cell and cell-matrix interactions. In such interactions the corresponding partner molecule recognising the sugar chain is often a sugar-specific protein (lectin). We present here evidence that the constituents of the SCO secretory product include proteins immunologically cross-reactive with certain plant lectins. Polyclonal antisera directed against Phaseolus vulgaris agglutinin-L (PHA-L) labelled the apically released RF-material of the rat SCO. Indirect ELISA studies shows in addition that anti-RF antisera bound to certain plant lectins (PHA-L, Con A). Dot spot assays demonstrated binding of anti-PHA-L to RF proteins. In Western blots of RF proteins anti-PHA-L, anti-RCA and anti-Con A bound to distinctive subsets of the RF protein fractions.

Animals↗
PubMed1990

Lectin-binding sites in the retina of the pig, baboon and cat.

There are notable interspecific differences in the lectin binding sites in the retina of mammals. In the porcine retina a distinct labeling of all the neurons of the stratum ganglionare is obtained by use of succinylated wheat-germ-agglutinin (WGA-S). In the baboon the stratum ganglionare does not label, though the entire inner plexiform layer can be demonstrated with WGA-S. In the cat WGA-S binds exclusively to the outer segments of the rods and cones. These specific differences will be compared with findings in the human retina [10] and discussed in connection with biochemical results obtained during our studies of the porcine retina.

Animals↗
PubMed1985

Distinctive structural and cytoskeletal properties of the long-surviving neurons in cell cultures of embryonic spinal cord.

A distinctive population of neurons survives for longer than 3 months in cell cultures of chick or rat spinal cord. These neurons form a minor proportion (1%) of the neurons initially developing in the cultures, but are the only ones to survive longer than 30 days in vitro. In addition to their longevity, they share important morphological and cytoskeletal characteristics, which render them distinctive as a group even in early cultures which contain numerous other neurons of short-term viability. Each long-surviving neuron projects one neurite of great length relative to its other neurites, or to those of the shorter-lived neurons, and the length of this neurite is maintained constant for many weeks in vitro. This well-defined morphological feature may indicate the lineage(s) of these neurons. Structurally these cells are very different to the shorter-lived neurons. They are rich in neurofilaments and contain very few microtubules, whereas the shorter-lived neurons contain few neurofilaments but many microtubules. These differences in cytoskeleton coincide exactly with the distinction between limited and prolonged survival in vitro, and the possibility is considered that cytoskeletal stability in the presence of numerous small inflows of calcium might underlie "hardiness" in vitro. The state of development of the long-lived neurons is considered in the context of their shared features, and it is suggested that they may provide a model in which the regulation of development of neuronal function can be analysed.

Animals↗
PubMedDate not supplied

Endocytic routes to the Golgi apparatus.

The endocytic routes of labelled lectins as well as cationic ferritin were studied in cells with a regulated secretion, i.e. pancreatic beta cells, and in constitutively secreting cells, i.e. fibroblasts and HepG2 hepatoma cells, paying particular attention to routes into the Golgi apparatus. Considerable amounts of internalised molecules were taken up into the trans Golgi network (TGN) and into Golgi subcompartments in all three cell types as well as in secretory granules of the pancreatic beta cells. The internalised materials did not pass rapidly the TGN and Golgi stacks, but were still present hours after internalisation, being then particularly concentrated in TGN-elements and in the transmost Golgi cisterna. Endocytosed materials reached forming secretory granules present in the TGN. Further, direct fusion between endocytotic vesicles and mature secretory granules was observed. Golgi subcompartments as well as endocytic TGN containing endocytosed materials were in close apposition to specialised regions of the endoplasmic reticulum. The Golgi apparatus including its parts containing endocytosed materials were transformed into a tubular reticulum upon treatment with the fungal metabolite Brefeldin A. Rarely, internalised material was observed in the lumen of the endoplasmic reticulum, thus providing evidence for an endocytic plasma membrane to endoplasmic reticulum route.

Animals↗