Fluorescence and computational studies of thymidine phosphorylase affinity toward lipidated 5-FU derivatives.

Thymidine phosphorylase (TP) is an enzyme that is up-regulated in a wide variety of solid tumors, including breast and colorectal cancers. It is involved in tumor growth and metastasis, for this reason it is one of the key enzyme to be inhibited, in an attempt to prevent tumor proliferation. However, it also plays an active role in cancer treatment, through its contribution in the conversion of the anti-cancer drug 5-fluorouracil (5-FU) to an irreversible inhibitor of thymidylate synthase (TS), responsible of the inhibition of the DNA synthesis. In this work, the intrinsic TP fluorescence has been investigated for the first time and exploited to study TP binding affinity for the unsubstituted 5-FU and for two 5-FU derivatives, designed to expose this molecule on liposomal membranes. These molecules were obtained by functionalizing the nitrogen atom with a chain consisting of six (1) or seven (2) units of glycol, linked to an alkyl moiety of 12 carbon atoms. Derivatives (1) and (2) exhibited an affinity for TP in the micromolar range, 10 times higher than the parent compound, irrespective of the length of the polyoxyethylenic spacer. This high affinity was maintained also when the compounds were anchored in liposomal membranes. Experimental results were supported by molecular dynamics simulations and docking calculations, supporting a feasible application of the designed supramolecular lipid structure in selective targeting of TP, to be potentially used as a drug delivery system or sensor device.

In vivo 19F MR imaging and spectroscopy for the BNCT optimization.

The aim of this study was to evaluate in vivo the boron biodistribution and pharmacokinetics of 4-borono-2-fluorophenylalanine ((19)F-BPA) using (19)F MR Imaging ((19)F MRI) and Spectroscopy ((19)F MRS). The correlation between the results obtained by both techniques, (19)F MRI on rat brain and (19)F MRS on blood samples, showed the maximum (19)F-BPA uptake in C6 glioma model at 2.5h after infusion determining the optimal irradiation time. Moreover, the effect of L-DOPA as potential enhancer of (19)F-BPA tumour intake was assessed using (19)F MRI.

Sonographic estimation of fetal liver weight: an additional biometric parameter for assessment of fetal growth.

A single fetal ultrasonogram was obtained between the 20th and 40th weeks of gestation in 327 pregnancies. Fetal body weight was calculated with standard methods and fetuses were classified as appropriate for gestational age (303 fetuses), large for gestational age (four fetuses), or small for gestational age (20 fetuses). Fetal liver weight was estimated on the basis of longitudinal, anteroposterior, and cephalocaudal liver dimensions multiplied by a constant (k) of 0.42 determined experimentally in a previous study of adult livers. Estimated liver weights in appropriate for gestational age fetuses were not statistically different from published standards based on autopsy findings (P < 0.005). Similar findings were obtained in two other normal pregnancies examined serially until delivery. Estimation of fetal liver weight appears to be an accurate and reproducible method and may enhance sonographic assessment of fetal growth abnormalities and conditions with fetal liver involvement.

[Experimental use of duplex Doppler ultrasonography in the evaluation of intestinal motility in occlusive syndromes]. / Impiego sperimentale del duplex Doppler nella valutazione della motilità intestinale nelle sindromi occlusive.

Intestinal motility is currently evaluated by means of clinical, radiologic and electromanometric methods. Of late, US has allowed to visualize the intestinal loops and their movements directly assessing wall patterns and endoluminal contents, as well as the degree of distension of the ileal loops; its diagnostic value is in fact well established in the study of such specific diseases of the GI tract as inflammatory conditions and neoplasms. On the contrary, the use of duplex-Doppler US to investigate bowel motility is quite new. We used duplex-Doppler US to evaluate intestinal peristalsis in 37 patients presenting with acute abdominal pain (15 patients with early mechanical obstruction; 13 patients with long-standing mechanical obstruction; 9 patients with paralytic ileus). In 29 patients the diagnosis was surgically confirmed; in 8 patients the diagnosis was established by means of other diagnostic techniques. The duplex-Doppler recordings showed typical patterns characterized by different degrees of signal intensity and frequency according to the type of obstruction (mechanical or paralytic ileus), to its duration (acute or long-standing), and to the site of Doppler sampling (proximal to or in the obstacle). As regards the correct identification of the cause of the obstruction, duplex-Doppler sensitivity and specificity were 85% and 100%, respectively. The positive predictive value was high (100%) whereas the negative predictive value was low (37.5%). Duplex-Doppler evaluation provides both qualitative and quantitative data about intestinal peristalsis, allowing true peristaltic movements to be discriminated from simple mixing movements of the bowel. The possibility to identify intestinal segments with different degrees of peristaltic activity seems very useful to detect the site of the obstacle in mechanical obstruction.

Duplex-Doppler evaluation of intestinal peristalsis in patients with bowel obstruction.

Duplex-Doppler was used to visualize intestinal peristalsis in 30 patients with intestinal distension. The series included 12 patients with acute mechanical obstruction, 13 with long-standing mechanical obstruction, and five with paralytic ileus. The Duplex-Doppler recordings showed several patterns characterized by different degrees of intensity and frequency of the signals according to the type of obstruction, its duration, and the site of Doppler sampling relative to the obstructed segment. Duplex-Doppler evaluation provided both qualitative and quantitative data about intestinal peristalsis, allowing differentiation between mechanical and paralytic ileus. The visualization of intestinal segments having different degrees of peristaltic activity proved useful in localizing the site of mechanical obstruction.

Real time ultrasonography of the gastric antrum.

This study aimed to evaluate whether serial ultrasound measurements of antral volumes are reproducible and, if so, whether they are representative of the entire gastric contents and reliably measure gastric emptying. The antral volume was measured in man after oral and intragastric administration of known amounts of 5% glucose solutions, and on two separate occasions in the same subjects, after the ingestion of a standardised solid-liquid meal (1050 kcal). Antral volume measurements were performed in both supine and upright positions; inter- and intraobserver measurement errors were also assessed. After ingestion or intragastric administration of equal amounts of liquid, antral volumes determined by ultrasound showed a wide intersubject variability. In each individual subject, however, a linear trend was found between the antral volume and amount of ingested or administered liquid. Intrasubject variability of antral volume measurements was at its minimum in fasting conditions and 300 minutes after ingestion of the solid-liquid meal. Intra- and interobserver variations and whether the patient was erect or supine did not affect measurements of antral volumes. These results support the use of real time ultrasound in determining the gastric emptying time. Results at fasting and 300 minutes after a solid-liquid meal are stable end points of measurement.

Eco-Doppler evaluation of intestinal peristalsis in normal and in some pathological conditions: preliminary data.

Duplex-Doppler sonography could be employed in the quantitative investigation of intestinal motility. Preliminary data indicate reproductivity of the method in normal subjects and possible clinical applications in some pathological conditions affecting intestinal transit. Particularly, the possibility to discriminate between segments at different peristaltic activity seems to be very useful in intestinal obstruction. Further studies are necessary to validate this method.

Extracorporeal shock-wave lithotripsy of biliary stones.

Extracorporeal shock-wave lithotripsy (ESWL) is the newest, the most rapid and most promising nonsurgical treatment for symptomatic patients with radiolucent (cholesterol) gallstones in a well opacified (functioning) gallbladder. About 10% of patients with gallstones fulfill the requirements to be selected for ESWL. Results indicate 78% of stone free patients at 12 months and 93% at 24 months, regardless of the size and number of treated stones. The cost-benefit trade-offs of ESWL versus conventional surgical treatment is still a matter of debate.

The dynamics of urban population.

The relative roles of natural increase and migration in determining the long-term dynamics of an urban population are considered. "Rogers' model is used to represent the simultaneous growth of a multiregional population. Exploiting the mathematical structure of the resulting system of difference equations, a perturbation theory for demographic models [is] outlined. This theory provides useful tools for analysing the sensitivity of stable population distribution and rate of growth to changes in the fundamental demographic parameters. With respect to the conventional approach to sensitivity analysis, it does not require the sometimes cumbersome calculation of matrix derivatives." A numerical example is given to demonstrate the method. (SUMMARY IN FRE AND ITA)

Modifications in pancreatic enzyme proportions following secretory stimulations.

The short-term influence of repeated secretory stimulations of the pancreas on pancreatic enzyme content was studied in the rat. The animals received 10 successive injections of either cholecystokinin-pancreozymin (CCK-PZ), secretin, CCK-PZ plus secretin, caerulein or pilocarpine. The pancreatic enzyme content was determined the next morning. CCK-PZ, with or without secretin, caerulein and pilocarpine had a similar influence increasing the chymotrypsinogen concentration in the pancreas twofold, while lipase and amylase concentrations increased by only 50 and 25%, respectively. Fasted and fed animals responded similarly. Secretin, a mostly ductal secretagogue, was without influence on the pancreatic enzyme composition. Thus, the mere stimulation of pancreatic protein secretion seems to result in a rapid change in enzyme composition in the pancreas.

Pancreatic enzyme secretion: nonspecific stimulation by duodenal mucosal extracts.

Felber et al. (Lancet 2: 185-188, 1974) reported that duodenal extracts obtained from rats fed a given meal induced the specific secretion of related pancreatic enzymes. Such an observation challenges the generally accepted theory of parallel secretion of pancreatic enzymes. Although these experiments were faithfully reproduced, no induction of specific enzyme secretion could be obtained. Moreover, comparison of the secretagogue potency of different preparations of duodenal extract, both in vivo (anesthetized rat) and in vitro (pancreatic lobules), demonstrated that in the original extraction procedure most of the secretagogue activity was lost. Finally, even the fully active extract failed to induce specific enzyme secretion. It is therefore unlikely that duodenal extracts from rats fed a specific meal can induce selective secretion of the related enzyme.

[Ultrasonic exploration of porto-caval shunts (author's transl)]. / Anastomoses porto-caves tronculaires. Exploration par ultrasons.

Ultrasonography was used to explore surgical porto-caval shunt in 10 patients. In 9 of these, the patency demonstrated by angiography was confirmed, the communication between the two veins being clearly visible on 9 transverse sections, 6 sagittal sections and 2 right frontal sections. In addition, the echograms supplied information on the size of the opening, the calibre of the inferior vena cava (which was usually dilated below the anastomosis) and, in some cases, the presence of thrombosis. Harmless and readily accepted by the patients, ultrasonography is likely to become one of the preferred methods for post-operative control of porto-caval shunts.