Chemoembolization in the therapy of hepatocarcinoma. A 3-year experience]

This study was aimed at evaluating the efficacy of chemoembolization (CE) to improve survival in patients with hepatocellular carcinoma (HCC). Our results were compared with the natural history of HCC. Sixty-two consecutive patients with HCC in Okuda's stages I and II underwent CE. Forty-seven patients were treated with CE alone; 9 patients had CE prior to surgery, and 6 patients had it after surgery because of recurrent HCC. One hundred and nine CEs (mean: 1.8 CEs/patient) were performed with Lipiodol UF, epirubicin and gelatin sponge. Actuarial survival was calculated considering Okuda's stage, neoplasm size, and evidence of pseudocapsule. The mean cumulative survival of the 47 patients treated with CE alone was 13.2 months; survival (+/- SE) at 12, 24 and 36 months was 0.75 (+/- 0.07), 0.46 (+/- 0.10) and 0.28 (+/- 0.12). Survival was not affected by Okuda's stage, neoplasm size, evidence of pseudocapsule (p > 0.05). Nevertheless, the patients with early HCC had better prognosis. Eighteen patients (42.9%) died during follow-up, 12 of whom (66.7%) from hepatic failure. The mean survival of patients with recurrence of HCC after surgery was 41 months (range: 24.8-74.9 months) since initial diagnosis of HCC, and 14.8 months (range: 7.1-29.6 months) since diagnosis of recurrence. Two of these patients died from hepatic failure. All the patients who underwent also surgery after CE are still alive (mean survival: 14.7 months). Histologic findings of resected specimens revealed viable neoplastic cells in all cases. Twenty-one major complications (20.2%) occurred in 18 patients (29%); the outcome of complications was favorable in all but one patient who died from sepsis. CE is a reliable and safe treatment for unresectable HCC. Small HCCs should be preferably treated with surgery or, alternatively, with percutaneous alcohol injection.     

Raman spectroscopic study of glutaraldehyde-stabilized collagen and pericardium tissue

For the first time, Raman spectroscopy has been employed to investigate formation of cross-links in collagen and porcine pericardium tissue upon glutaraldehyde (GA) treatment. GA treatment causes a very high fluorescence background, which overlaps Raman bands. It has been found that short fixation time, i.e. 2 h, reduces background radiation significantly, providing new possibilities for studying changes in molecular structure of collagen upon GA modification. The observed changes in position and intensity of Raman bands allowed us to recognize different types of GA-collagen interactions. Strong spectral evidence has been found for the peptide contribution to the formation of the GA-collagen cross-links and for the formation of secondary amines via Schiff base intermediates, and pyridinium-type cross-links. The results also revealed that different hydration levels and a more complex structure of intact tissue in comparison to collagen preparation strongly influence the formation of a GA cross-linking network, e.g. ether-type bond is preferred to form in a less hydrated collagen preparation. Our results have shown that GA treatment causes an increase in water content of pericardium tissue and collagen.     

Incidence and identification of Klebsiella planticola in clinical isolates with emphasis on newborns

Studies conducted in France and Germany suggest that up to 19% of clinically identified Klebsiella sp. are actually Klebsiella planticola, an environmental species that has been attributed to two cases of septicemia, with a rare isolate of Klebsiella terrigena (0. 4%) being identified. A 1-year survey of newborns on a neonatal ward, also conducted in Germany, reported that 72% of Klebsiella sp. were Klebsiella oxytoca and 8.7% were K. planticola. The tests necessary to identify these species are not found in most clinical identification schemes or in the database matrices of most commercial identification products. To determine the incidence of unrecognized K. planticola among the Klebsiella sp. isolates in our collection, we used the battery of seven supplemental tests amended from the work of Monnet and Freney to test 352 stock isolates and 84 fresh clinical isolates from four local hospitals. After testing 436 strains of Klebsiella, only one strain was identified as a possible K. planticola and none was identified as K. terrigena. We tested an additional 43 stock strains of K. oxytoca isolated from newborns by using eight biochemical tests and found one additional strain of K. planticola. The occurrence of K. planticola in our collection is far less frequent than that observed in other countries.     

Bone marrow-derived mesenchymal stem cells in repair of the injured lung

We sought to determine whether an intact bone marrow is essential to lung repair following bleomycin-induced lung injury in mice, and the mechanisms of any protective effects conferred by bone marrow-derived mesenchymal stem cell (BMDMSC) transfer. We found that myelosupression increased susceptibility to bleomycin injury and that BMDMSC transfer was protective. Protection was associated with the differentiation of engrafted BMDMSC into specific and distinct lung cell phenotypes, with an increase in circulating levels of G-CSF and GM-CSF (known for their ability to promote the mobilization of endogenous stem cells) and with a decrease in inflammatory cytokines. In vitro, cells from injured, but not from normal, mouse lung produced soluble factors that caused BMDMSC to proliferate and migrate toward the injured lung. We conclude that bone marrow stem cells are important in the repair of bleomycin-injured lung and that transfer of mesenchymal stem cells protects against the injury. BMDMSC localize to the injured lung and assume lung cell phenotypes, but protection from injury and fibrosis also involves suppression of inflammation and triggering production of reparative growth factors.     

Inflammatory mediators are insufficient for full dendritic cell activation and promote expansion of CD4+ T cell populations lacking helper function

Dendritic cells (DCs) can be activated directly by triggering of receptors for pathogens or, indirectly, by exposure to inflammatory signals. It remains unclear, however, whether the two pathways result in qualitatively similar DCs or lead to equivalent adaptive immune responses. Here we report that indirect activation by inflammatory mediators generated DCs that supported CD4(+) T cell clonal expansion but failed to direct T helper cell differentiation. In contrast, exposure to pathogen components resulted in fully activated DCs that promoted T helper responses. These results indicate that inflammation cannot substitute for contact with pathogen components in DC activation and suggest that the function of pattern recognition by DCs is to couple the quality of the adaptive immune response to the nature of the pathogen.     

Bilateral syringeal coupling during phonation of a songbird

The syrinx of oscine birds ("true songbirds") is a double vocal organ, and each side has generally been presumed to function independently under separate neural control during phonation. A significant counterexample is demonstrated here in the production of a common vocalization by the black-capped chickadee (Parus atricapillus), in which the 2 acoustic sources of the syrinx interact in a nonlinear fashion. The chickadee produces a sound with multiple frequency components that superficially resemble harmonics. An analysis of vocal production after unilateral and bilateral syringeal denervation shows instead that these frequency components are sum and difference frequencies, or heterodyne frequencies, resulting from cross-modulation between the 2 syringeal sides. A limited form of this bilateral coupling may be achieved after unilateral denervation of either syringeal side but not after bilateral denervation. Unilaterally denervated birds are capable of significant improvement in coupling after 10 d, too short a period for neural regrowth. These results suggest that coupling arises from a passive physical interaction between the 2 syringeal sources which is activated or regulated in some fashion by neural control from either side.     

Comparison of α-Tocopherol, α-Tocopherol Acetate,and α-Tocopheryl Polyethylene Glycol Succinate 1000 Absorption by Caco-2 TC7 Intestinal Cells

(1) Background: vitamin E is often supplemented in the form of tocopherol acetate, but it has poor bioavailability and can fail to correct blood tocopherol concentrations in some patients with severe cholestasis. In this context, α-tocopheryl polyethylene glycol succinate 1000 (TPGS) has been of value, but very little is known about the mechanisms of its absorption. The aim of our work was to evaluate the mechanisms of absorption/secretion of TPGS compared to tocopherol acetate (TAC) and α-tocopherol by human enterocyte-like Caco-2 TC7 cells. (2) Methods: two weeks post-confluence Caco-2 cells were incubated with tocopherol- or TAC- or TPGS-rich mixed micelles up to 24 h and, following lipid extraction, TAC and tocopherol amounts were measured by high performance liquid chromatography (HPLC) in apical, cellular, and basolateral compartments. (3) Results: at equivalent concentrations of tocopherol in the apical side, the amounts of tocopherol secreted at the basolateral pole of Caco-2 cells are (i) significantly greater when the tocopherol is in the free form in the micelles; (ii) intermediate when it is in the TAC form in the micelles (p < 0.001); and (iii) significantly lower with the TPGS form (p < 0.0001). Interestingly, our results show, for the first time, that Caco-2 cells secrete one or more esterified forms of the vitamin contained in TPGS at the basolateral side.