Application of image-guided surface coil P-31 MR spectroscopy to human liver, heart, and kidney

Localized phosphorus-31 magnetic resonance (MR) spectroscopy in humans has previously been accomplished with surface coils by means of depth-resolved surface coil spectroscopy or rotating frame experiments, in which the extent of tissue sampled critically depends on surface coil placement. The authors' goal was to modify the surface coil image-selected in vivo spectroscopy (ISIS) experiment to accomplish three-dimensional volume selection through application of selective pulses in the presence of B0 gradients. Advantages of ISIS include the ability to use proton images to define the volume of interest (VOI) and reduced dependence on exact positioning of the surface coil. However, rapid replication of the surface coil ISIS experiment can cause spectral contamination from signals originating outside the VOI. A modified version of the ISIS experiment was developed to alleviate contamination under conditions of rapid replication. Applications of localized P-31 MR spectroscopy for observation of high-energy phosphorus metabolites are presented in human liver, heart, and transplanted and normal kidney.     

Cellular models for the screening and development of anti-hepatitis C virus agents

Investigations on the biology of hepatitis C virus (HCV) have been hampered by the lack of small animal models. Efforts have therefore been directed to designing practical and robust cellular models of human origin able to support HCV replication and production in a reproducible, reliable and consistent manner. Many different models based on different forms of virions and hepatoma or other cell types have been described including virus-like particles, pseudotyped particles, subgenomic and full length replicons, virion productive replicons, immortalised hepatocytes, fetal and adult primary human hepatocytes. This review focuses on these different cellular models, their advantages and disadvantages at the biological and experimental levels, and their respective use for evaluating the effect of antiviral molecules on different steps of HCV biology including virus entry, replication, particles generation and excretion, as well as on the modulation by the virus of the host cell response to infection.     

Metabolism and CYP-inducer properties of astaxanthin in man and primary human hepatocytes

Previous investigations in the rat have shown that the non-provitamin A carotenoid astaxanthin is metabolized into 3-hydroxy-4-oxo-beta-ionone and 3-hydroxy-4-oxo-7,8-dihydro-beta-ionone and, in addition, is a potent CYP1A gene inducer. Here we investigated the metabolism of this compound as well as its capacity to induce CYP genes in primary cultures of human hepatocytes. Free metabolites of 14C-astaxanthin produced in this cellular model were purified by high pressure liquid chromatography (HPLC) and identified by gas chromatography-mass spectrometry (GC-MS) analyses as 3-hydroxy-4-oxo-beta-ionol and 3-hydroxy-4-oxo-beta-ionone. In addition, deconjugation of polar compounds by glusulase and further analyses with HPLC and GC-MS revealed four radiolabeled metabolites including: 3-hydroxy-4-oxo-beta-ionol, 3-hydroxy-4-oxo-beta-ionone, and their reduced forms, 3-hydroxy-4-oxo-7, 8-dihydro-beta-ionol and 3-hydroxy-4-oxo-7,8-dihydro-beta-ionone. The same four metabolites were identified in human plasma from two volunteers who had orally taken 100 mg astaxanthin 24 h before blood collection. In cultured hepatocytes, astaxanthin was a significant inducer of the major cytochrome P450 enzyme, CYP3A4 as well as of CYP2B6, but not of other CYPs, including those from CYP1A and CYP2C families. The lack of autoinduction of astaxanthin metabolism in human hepatocytes suggests that neither CYP3A4 nor CYP2B6 contribute to the formation of metabolites. We conclude that metabolism of astaxanthin and its CYP-inducing capacity are different in humans and in rats. The novel methodology used in our studies could be extended to evaluating the role of metabolites of more important carotenoids such as beta-carotene in differentiation and carcinogenicity.     

Late intestinal fistula following implantation of parietal abdominal prostheses]

STUDY AIM: The aim of this retrospective study was to describe an unusual complication of the nonabsorbable meshes used for repair of incisional hernia or inguinal hernia. PATIENTS AND METHODS: This study included eight observations of intestinal fistulas that occurred between 1 and 13 years after using Mersilène (Dacron) mesh for repair of an incisional hernia (7 cases) and an inguinal hernia (1 case). There were 6 men and 2 women (mean age: 58 years, range: 35-85 years) with an external intestinal fistula (n = 6) or an internal intestinal fistula (n = 2). All the patients required a reoperation for extraction of the mesh and treatment of the bowel injuries. RESULTS: There was one secondary death in a 85 years old woman in relation with a vascular complication after incomplete excision of the prosthesis. In five patients out of six, there was a recurrence of the incisional hernia. CONCLUSION: The intestinal fistulas associated with prosthetic repair of the abdominal wall are mostly observed with intraperitoneal mesh but this factor is not exclusive. Their frequency after repair of incisional or inguinal hernia with non absorbable mesh is estimated between 0.3 and 3.5%. The use of nonabsorbable mesh should be limited to the indications of strict necessity, without any septic context or emergency surgery. The contact of the mesh with the bowel should be formally avoided.     

Cardiac natriuretic peptide response to water restriction in the hormonal adaptation of two semidesert rodents from West Africa (Steatomys caurinus, Taterillus gracilis)

Two African rodents, Taterillus gracilis and Steatomys caurinus, native to regions of alternate dry and wet seasons, were studied under laboratory conditions. These species differ in estivation behavior, one undergoing pseudoestivation and the other strong estivation. One group of animals of each species was provided with unlimited access to seed and vegetables rich in water, mimicking the food availability of the wet season (control group). A second group of animals of each species was subjected to water restriction for 8 days, mimicking the natural drought that occurs during the dry-hot season. The effects of water restriction on osmoregulation and body water content were assessed from hematocrit, and plasma and urinary osmolalities (PO, UO). Whether the natriuretic peptide system was modified by the osmoregulator adaptation to aridity of these semidesert rodents was examined from measurements of atrial natriuretic peptide (ANP) levels in plasma, atria, and ventricles, in parallel with morphological studies. In both species, UO was increased by water restriction. In water-deprived T. gracilis, ANP levels were about twice (right atria: 1.08 +/- 0.16 microg/mg protein vs control: 0.40 +/- 0.06 microg/mg protein) and plasma concentrations half (0.28 +/- 0.06 ng/ml vs control: 0.64 +/- 0.07 ng/ml) those in control animals. In S. caurinus these variables were not affected by water availability (right atria water restricted: 2. 20 +/- 0.15 microg/mg protein vs control: 2.86 +/- 0.37 microg/mg protein; plasma ANP water restricted: 0.80 +/- 0.12 ng/ml vs control: 0.90 +/- 0.16 ng/ml). Consistent with these quantitative results, immunohistochemical and ultrastructural observations showed an increase in immunostaining for both the N- and the C-terminal ANP and a larger number of granules in the atria of T. gracilis following water restriction, whereas there was no visible change in S. caurinus. Thus, water restriction induced a decrease in ANP secretion in T. gracilis, increasing cardiac storage alongside a reduced urine production. In contrast, in S. caurinus, the natriuretic system was not affected by an 8-day period of water restriction.     

Prognostic impact of bulky mediastinal lymph nodes (N2>2.5 cm) in patients with locally advanced non-small-cell lung cancer (LA-NSCLC) treated with platinum-based induction chemotherapy

A group of 70 patients with locally advanced non-small-cell lung cancer (LA-NSCLC), treated in different phase II-III trials with platinum-based chemotherapy in two institutions, have been evaluated to identify potential baseline prognostic factors predicting their survival. The eligibility criteria were patients with stage IIIA (N2)-IIIB, Eastern Cooperative Oncology Group performance status 0.1 and less than 5% weight loss. All 37 patients with stage IIIA(N2) were treated with platinum-based induction chemotherapy followed by surgery plus radiotherapy if no progression was observed. The other 33 patients with stage IIIB were treated with platinum-based induction chemotherapy followed by conventional fractionation radiotherapy if no progression was observed. The overall response rate to induction chemotherapy was 40%. Median survival of the 70 patients was 13 months, with a 4-year survival of 15%. At univariate analysis, two prognostic factors correlated with survival: partial or complete response to induction chemotherapy (P<0.00001) and bulky mediastinal lymph nodes (N2>2.5 cm) (P=0.03). At multivariate analysis, only the response to induction chemotherapy retained statistical significance (P=0.00001). Randomized well-balanced prospective trials considering initially mediastinal N2 node size are needed to clearly establish the role of chemotherapy, surgery and radiotherapy in LA-NSCLC.