Treatment of hepatocellular carcinomas by thermal ablation and hepatic transarterial chemoembolization.

Local tumor recurrence after thermal ablation of hepatocellular carcinoma (HCC) can impact on overall survival and are very closely linked to partial treatment of the primary lesion or to potential microvascular invasion or satellite micronodules located close to the main lesion. The diagnosis of these liver metastases close to the primary lesion on CT and MRI is difficult and their incidence, number and spread throughout the liver correlates with diameter of primary tumor. Tumor diameter is currently the key factor to predict whether or not thermal ablation of HCC will be complete or not. It has now been shown for monopolar radiofrequency ablation that this therapy alone is sufficient to effectively treat single HCCs<3cm in diameter provided that liver micrometastases are not present. If the HCC is>3cm in size, multifocal or in the case of tumor recurrence, overall survival and recurrence-free survival results are better if monopolar radiofrequency ablation is combined with hepatic trans-arterial chemoembolization. The timing of this combination of treatments probably influences its effectiveness on tumor and tolerability and remains to be assessed.

Quality of life improvement in Latin American patients suffering from chronic venous disorder using a combination of Ruscus aculeatus and hesperidin methyl-chalcone and ascorbic acid (quality study).

AIM: The present study assessed the effect of Ruscus aculeatus, hesperidin methyl-chalcone and ascorbic acid (HMC-AA), in the treatment of chronic venous disorders (CVD) in Latin American patients. METHODS: This study is an observational, single arm, multicentric and prospective trial. Patients suffering from CVD and belonging to C0s-C3 Clinical Etiological Anatomical and Physiopathological (CEAP) classes were included. Patient profiles, risk factors, clinical symptomatology and quality of life (QoL) assessed by SF-12 and CIVIQ questionnaires were evaluated at inclusion and after 12-week treatment. RESULTS: The main factors influencing the previous management of patients were age, gender, body mass index (BMI), familial history, physical activity, exposure to heat, heavy loads lifting, profession and clinical characteristics. All clinical symptoms significantly improved with treatment and, as BMI and CEAP classes increased. Ankle circumferences decreased over time, correlating with BMI and CEAP classes. The physical and psychological dimensions of the SF-12 score significantly increased over time and improved within each CEAP class. The CIVIQ score significantly improved over time, correlating with age and CEAP classes. CONCLUSION: A 12-week treatment with Ruscus aculeatus HMC-AA showed a significant decrease in the clinical symptoms and a significant improvement in the QoL of patients with CVD.

Assessment of quality of life in Mexican patients suffering from chronic venous disorder - impact of oral Ruscus aculeatus-hesperidin-methyl-chalcone-ascorbic acid treatment - 'QUALITY Study'.

OBJECTIVES: The present study assessed the effect of Ruscus aculeatus-hesperidin-methyl-chalcone-ascorbic acid (HMC-AA) on the quality of life (QoL) of patients suffering from chronic venous disorders (CVDs). METHODS: An observational, multicentre and prospective study was performed with 917 Mexican patients suffering from CVD. Patients were treated with R. aculeatus-HMC-AA. After 12 weeks of treatment, the physicians then assessed the patients' symptoms and QoL using Short Form (SF-12) and Chronic Venous Insufficiency (CIVIQ) auto-questionnaires. RESULTS: Patients were mainly women (86.7%), overweight or obese (72.7%) or C2 (39.3%)-C3 (27.6%). All symptoms and ankle circumferences significantly improved over time, with increasing clinical, aetiological, anatomical and pathophysiological (CEAP) classes and body mass index (BMI) (P < 0.001). Concerning QoL, all dimensions of the SF-12 score significantly improved over time (P < 0.001). Moreover, the CIVIQ scores significantly improved (P < 0.001) with increasing BMI (P < 0.002) and CEAP classes (P < 0.05). CONCLUSION: R. aculeatus-HMC-AA significantly improved the symptoms and QoL of CVD patients.

Inhibition of U-937 membrane-associated cathepsin G by GP120 (IIIB) and V3 loop-derived peptides from several strains of HIV-1.

A cell surface-associated cathepsin G has been reported to be a possible complementary factor for HIV-1 infection of U-937 cells. The effect of recombinant gp120 (IIIB) and a series of V3 loop peptides derived from the sequence of different strains of HIV on the activity of U-937 cathepsin G was assayed. The sequence on the N-terminal side of the highly conserved GPGRAF V3 loop segment was required for interaction with cathepsin G. The inhibition was stable for several hours and there was no cleavage of the peptides derived from the HIV-1(IIIB) strain. Recombinant gp120 (IIIB) also remained uncleaved after incubation with cathepsin G for 3 h, but some cleavage occurred, generating 2 fragments (50 kDa and 70 kDa), after 16 h. Linear peptides derived from HIV-1 Mal, ELI, MN, CDC4 and SF162 strains, and consensus V3 peptides all had inhibitory properties towards cathepsin G, although they were significantly cleaved after one hour. The cleavage site was at the carboxy-terminus of Tyr323 which is conserved in all these HIV-1 strains but not in HIV-1(IIIB). There was no cleavage at the Arg residue of the GPGRAF sequence, whatever the V3 peptide sequence, the amount of proteinase, or the incubation time. We conclude that the inhibition of membrane-associated cathepsin G of U-937 cells by the gp120 V3 loop of HIV-1 does not occur via a Kunitz-type mechanism, and that the proteinase-V3 loop interaction does not result in a significant cleavage of the V3 loop, though it has been suggested that this event is required for the entry phase of the virus.

Identification of the U-937 membrane-associated proteinase interacting with the V3 loop of HIV-1 gp120 as cathepsin G.

We have purified a serine proteinase from the membrane of U-937 cells that was inhibited in a tight-binding manner by recombinant gp120 and by peptides mimicking the V3 loop of gp120 [(1993) FEBS Lett. 317, 167-172]. This proteinase has now been characterized, both structurally and functionally. It has a dual trypsin- and chymotrypsin-like specificity, and N-terminal sequence analysis of the first 32 residues indicates complete identity with leukocyte cathepsin G. Cathepsin G-like material was located at the surface of U-937 cells using a monoclonal antibody directed against leukocyte cathepsin G, and polyclonal anti-cathepsin G antibodies precipitated the purified proteinase. However, the U-937 enzyme differs slightly from commercial leukocyte cathepsin G in its apparent M(r) because of different glycosylation. No other protein structurally related to cathepsin G was found upon screening a U-937 cDNA library using several oligonucleotide probes constructed from the membrane proteinase N-terminal amino acid sequence. The possible interaction of a cathepsin G-like proteinase at the surface of U-937 cells with the V3 loop of HIV-1 gp120 is discussed.

Interaction between a membrane-associated serine proteinase of U-937 monocytes and peptides from the V3 loop of the human immunodeficiency virus type 1 (HIV-1) gp120 envelope glycoprotein.

A trypsin-like proteinase which is inhibited by recombinant gp120 and by synthetic peptides of various lengths spanning the conserved sequence of the V3 loop has been purified and partially characterized from a U-937 cell membrane extract. V3 loop peptides behave as competitive inhibitors of the enzyme, while gp120 exerts a tight-binding inhibition, reacting in stoichiometric amounts with the proteinase to provide significant inhibition. Though the properties of the U-937 membrane proteinase towards gp120 and synthetic peptides of the V3 loop resemble those of the Molt-4 T-cell tryptase TL2, these two proteinases differ by their physicochemical properties and their susceptibility to other inhibitors of serine proteinases. These results give support to the concept of a membrane-associated proteinase as a complementary or alternative receptor to the CD4, for allowing virus to enter host cells and thus spreading HIV infection.

Factors affecting the spatial distributions of thinly encrusting sponges from temperate waters.

Interactions along borders between pairs of species of abundant thinly encrusting sponges from a hard substratum subtidal community were investigated. Over a nine month study period the majority of borders between species did not shift in position. Several different forms of overgrowth were found but none lead to the death of the underlying species or subsequent attainment by the overgrower of the space occupied by the underlying sponge. Overgrowth in these types of sponges may be a defensive strategy aimed at maintaining presently occupied space. Only one species, Aplysilla rosea, gained space along borders and this occurred without any overgrowth of the space-losing species. This Dictyoceratid sponge was found to be very toxic toward a variety of indicator organisms and it is possible that these toxins form the basis of the mechanism behind its success in maintaining and obtaining space. In this community free space (unoccupied primary space) was available over 16% of the substratum due primarily to the grazing activities of an abundant echinoid Evechinus chloroticus. The encrusting sponges were damaged experimentally to investigate the influence of their different rates of regeneration on the outcome of competitive interactions. Again, Aplysilla rosea gained the most space but some species which did not gain space along borders gained space from neighbouring sponges in this experiment. Aplysilla rosea might be expected to be the dominant species in this community but this sponge was one of the least abundant species in this community. Although competitive interactions along sponge borders and clearings are useful to predict some aspects of sponge spatial patterns, other life history processes such as recruitment may be more important.

GROWTH AND REGENERATION RATES IN THINLY ENCRUSTING DEMOSPONGIAE FROM TEMPERATE WATERS.

Thinly encrusting species of subtidal sponge grow at slow but measurable rates over natural surfaces by lateral spreading. Of the eleven species studied here, Aplysilla rosea had the highest undisturbed rate of growth and Microciona sp. the lowest with an overall negative change in size. Using the mean growth rate it can be estimated that the largest sponge patches observed in the field may be over seventy years old. Growth rates of individual patches were varied but this variation was not synchronous within a species nor did it show any regular temporal pattern. Similarly, no relation between the normal thickness of the species, the wet weight, or true organic content of the species with undisturbed rates of growth could be found. However, the mean patch size of the species was correlated with the undisturbed growth rates. If the tissues of the sponges were damaged, rapid regeneration was initiated at rates many times greater than the undisturbed growth rate of the species. It was also found that even very small sponge patches could recover after almost all living tissue was scraped from the rock.