Conformal Invariance in Water-Wave Turbulence.

We experimentally investigate the statistics of zero-height isolines in gravity wave turbulence as physical candidates for conformal invariant curves. We present direct evidence that they can be described by the family of conformal invariant curves called stochastic Schramm-Löwner evolution (or SLE_{κ}), with diffusivity κ=2.88(8). A higher nonlinearity in the height fields is shown destroy this symmetry, though scale invariance is retained.

Non-Cytotoxic Sulfated Heterorhamnan from Gayralia brasiliensis Green Seaweed Reduces Driver Features of Melanoma Metastatic Progression.

Melanoma is a form of skin cancer with high mortality owing to its fast progression and metastatic capacity. The treatments available nowadays are only palliative in advanced stages of the disease. Thus, alternative therapies for cancer treatment are in demand, and molecules from natural sources, such as polysaccharides, could represent new possible therapeutic approaches. Polysaccharides of freshwater and marine algae with biological activities, such as antitumor properties, are greatly reported in the scientific literature. In the present study, a sulfated heterorhamnan obtained from the green seaweed Gayralia brasiliensis (Gb1 fraction) was chemically characterized and its biological activities in the B16-F10 murine melanoma cell line were evaluated. The Gb1 polysaccharidic fraction tested concentrations presented low or absence of cytotoxicity to B16-F10 cells and neither cell proliferation nor cell cycle were altered. Interestingly, Gb1 treatment decreased B16-F10 cells migration and invasion capabilities and CD44 labeling, showing to be a promising compound for further in vitro and in vivo antitumor studies.

NMR and rheological study of Aloe barbadensis partially acetylated glucomannan.

The structural and rheological properties of the Aloe extract (AE) and the polysaccharidic fraction (PF) obtained from the leaves pulp of Aloe barbadensis Miller were investigated. Structural analyses carried out by composition, methylation analysis and NMR spectroscopy showed that PF is mainly constituted by a partially acetylated 4-linked ß-d-glucomannan. The acetyl groups are located at C-2, C-2 and C-3, C-3 and/or C-6. The acetylation pattern of this type of polysaccharide was for the first time established using bidimensional NMR analyses. AE and PF aqueous solutions at 25°C showed a non-Newtonian behavior (with pseudoplastic characteristics), however PF showed higher apparent viscosity than AE. Dynamic oscillatory analyses showed that both samples, at the same concentration, behaved as a concentrated solution. PF presented higher values of G' compared with those of AE and this behavior could be consequence of its higher content in partially acetylated glucomannan.

Co-culture of microalgae, cyanobacteria, and macromycetes for exopolysaccharides production: process preliminary optimization and partial characterization.

In this study, the biomass and exopolysaccharides (EPS) production in co-cultures of microalgae/cyanobacteria and macromycetes was evaluated as a technology for producing new polysaccharides for medical and/or industrial application. Based on biomass and EPS productivity of monocultures, two algae and two fungi were selected and cultured in different co-culture arrangements. The hydrosoluble EPS fractions from mono- and co-cultures were characterized by ¹³C NMR spectroscopy and gas chromatography coupled to mass spectrometry and compared. It was found that co-cultures resulted in the production of an EPS different from those produced by monocultures, showing fungal predominance with microalgal/cyanobacterial traces. Co-cultures conditions were screened (temperature, agitation speed, fungal and microalgae inoculation rate, initial pH, illumination rate, and glucose concentration) in order to achieve maximum biomass and EPS production, resulting in an increase of 33 and 61% in exopolysaccharides and biomass productions, respectively (patent pending).

[Game as a strategy to educate youngsters about disability]. / Il gioco come metodologia di educazione alla disabilità.

Disability is an interesting social topic even if it is sistematically neglected in common educational programs that are addressed prevalently to disabled person and not to all community. But only a community approach can promote a full social inclusion of all its members. Game is an easy and funny method to improve social participation and control emotions that this topic can hide. Aim of this article is to illustrate how some sensitive and motorial experiences can be easily proposed in a young community to explicit educational finalities.

Agar from Gracilaria gracilis (Gracilariales, Rhodophyta) of the Patagonic coast of Argentina--content, structure and physical properties.

Milled summer thalli of Gracilaria gracilis from Argentina were sequentially extracted with water at room temperature (RTW1-3), 70 degrees C (W701-3) and 90 degrees C (W901-2). Both W701 and W901 consisted of high molecular weight polysaccharides (ca. 540,000Da), but polydispersity was higher for the major product W701 (yield, 72% of the recovered). Structural analyzes by methylation and (13)C NMR spectroscopy revealed that W701 was mainly agarose. Alkaline treatment, together with structural analyzes, indicated a negligible proportion of precursor l-galactose 6-sulfate residues in this product, while they were clearly detected in the (13)C NMR spectra of RTW2-3. The presence of floridean starch in W901 had an antagonistic effect on its gel strength, which resulted nearly three times lower than that of fraction W701. Ultrastructural observation by transmission electron microscopy showed that, after extraction with hot water, a partial loss of cell wall stratification and disorganization of the cuticle had occurred. Final cellular debris exhibited swelling in the microfibrillar component. After this first thorough study of the chemical composition and physical properties of the products of G. gracilis from Bahía Bustamante we conclude that a good quality agarose is obtained in high yield after extraction with water at 70 degrees C without the requirement of alkaline pretreatment, which usually produces degradation of the polysaccharide.

Production and characterization of the exopolysaccharides produced by Agaricus brasiliensis in submerged fermentation.

The aim of the work was to study the production of the exopolysaccharides by Agaricus brasiliensis and the isolation of exopolysaccharides (EPSs) with biological effects. A brasiliensis LPB03 was cultured in submerged fermentation in a medium containing glucose, yeast extract, hydrolyzed soybean protein, and salts (pH 6.1) at 29 degrees C and 120 rpm for 144 h. The maximum biomass and EPS yield was 7.80 +/- 0.01 and 1,430.70 +/- 26.75 mg/L, respectively. To isolate the produced EPSs, two methods were compared: (1) with alcohol precipitation and (2) treatment with tricloroacetic acid (TCA), followed by alcohol precipitation. The use of TCA facilitated the purification of the EPS, reducing the amount of the contaminant soy proteins. For monosaccharide identification, the EPSs were hydrolyzed, derivatized to alditol acetates, and analyzed by gas chromatography (GC) and GC-mass spectrometry, which showed the presence (in molar percentage) of mannose (58.7), galactose (21.4), and glucose (13.1) as major sugars, with lower amounts of rhamnose (3.9) and xylose (2.8). Scanning electron microscopy was used to observe the morphological structure of the EPS. The experiments in vivo including EPS in the mice diet during 8 weeks indicated the hipocholesteremic and hypoglycemic effects.

The antiviral activity of sulfated polysaccharides against dengue virus is dependent on virus serotype and host cell.

Two homogeneous sulfated polysaccharides obtained from the red seaweeds Gymnogongrus griffithsiae and Cryptonemia crenulata, the kappa/iota/nu carrageenan G3d and the dl-galactan hybrid C2S-3, were assayed for their antiviral properties against the four serotypes of dengue virus (DENV) in different host cell types. Both seaweed derivatives were selective inhibitors of DENV-2 multiplication in Vero cells with inhibitory concentration 50% (IC50) values around 1 microg/ml and selectivity indices > 1000. The compounds had a lower antiviral effect against DENV-3 (IC50 values in the range 13.9-14.2 microg/ml), an even lower effect against DENV-4 (IC50 values in the range 29.3 to > 50 microg/ml) and were totally inactive against DENV-1. With respect to the host cell, the polysulfates were inhibitors of DENV-2 and DENV-3 in the human hepatoma HepG2 and foreskin PH cells, with similar antiviral effectiveness as in Vero cells, but were totally inactive in mosquito C6/36 HT cells. Mechanistic studies demonstrated that G3d and C2S-3 were active DENV-2 inhibitors only when added together with the virus or early after infection, and both initial processes of virus adsorption and internalization are the main targets of these compounds. Therefore, the variations in antiviral activity of the polysaccharides depending on the viral serotype and the host cell may be ascribed to differences in the virus-cell interaction leading to virus entry.

B-type natriuretic peptide in athletes performing an Olympic triathlon.

AIM: Brain natriuretic peptide (BNP) is a cardioactive molecule produced in the myocardium. BNP is a sensitive marker of cardiac failure and its measurement in blood could be useful to the diagnosis and the treatment of this disease. Sporting activities, especially endurance ones, can induce cardiac problems, owing to the high workload for the myocardium during long and ultralong heavy effort. There are 2 papers describing the behavior of BNP in endurance events. BNP was elevated in marathoners, immediately after the race and also after 4 h. We studied the behavior of BNP in the triathlon, which is a complex sport characterized by 3 different activities (swimming, cycling, running). METHODS: We recruited 49 athletes, all males, except for 4 females; 2 athletes did not finish the race and were not included in the statistical analysis in 2 different competitions. In these subjects we measured BNP using an immunological method before and after a triathlon. RESULTS: No statistical significance between BNP values, before and after the triathlon, was found. CONCLUSIONS: We found no significant differences between pre- and postcompetition BNP values. Moreover, the range of values in both the blood drawings are similar of those of the general population, representing the biological variability of the analyte. The values in regularly trained athletes,, are not different from the general population and BNP is not modified by a triathlon, a typical endurance sport performance. We can underline that BNP increases in plasma are induced by heavy pathologies and are not influenced by physical activities, even strenuous ones.

Protective effect of a natural carrageenan on genital herpes simplex virus infection in mice.

In the present study, the protective effect of 1T1, a lambda-carrageenan extracted from the red seaweed Gigartina skottsbergii was evaluated in a murine model of herpes simplex virus type 2 (HSV-2) genital infection. Six to eight-week-old female BALB/c mice were intravaginally inoculated with a lethal dose of HSV-2 (MS strain) and pre- or post-infection treated with different doses of a 10mg/ml solution of 1T1. A single topical administration of 1T1 shortly before infection of BALB/c mice with HSV-2 protected 9 out of 10 mice from HSV-2-induced lesions and mortality, compared with only 10% survival in control mice. In addition, 1T1 produced a total blockade in virus shedding in the vaginal secretions. When 1T1 pre-treatment was reinforced with a second dose 2h after infection, total protection was observed even when the prophylactic administration had taken place at 60min before infection. The irreversible virucidal action of 1T1 against herpes virus seems to be responsible of its protective effect against virus replication and mortality following vaginal HSV-2 infection.

Structural studies on fucoidans from the brown seaweed Sargassum stenophyllum.

The brown seaweed Sargassum stenophyllum biosynthesizes two different sets of fucoidans. One of them is characterized by higher percentages of glucuronic acid and fewer sulfate groups, which are situated on different sugar units. alpha-L-Fucose was the major component but other sugars like beta-D-galactose, beta-D-mannose, alpha-D-glucuronic acid, alpha-D-glucose and beta-D-xylose were also in substantial amounts. Fucoidans from the other set contain small amounts of alpha-D-glucuronic acid and high percentages of sulfate groups, which are concentrated on the fucose residues, with only fucose and galactose as major components. Structural studies of one fucoidan from each set suggest that these products have a general basic structure that has a formal resemblance to that of the fucosylated chondroitin sulfates from the body wall of sea cucumbers, namely, a linear core (formed mainly by (1-->6)-beta-D-galactose and/or (1-->2)-beta-D-mannose units) with branched chains of 'fucans' (formed by (1-->3) and/or (1-->4)-alpha-L-fucose, (1-->4)-alpha-D-glucuronic acid, terminal beta-D-xylose and, sometimes, (1-->4)-alpha-D-glucose). In fucoidans from the second set, the 'core' is reduced to short galactan chains.

Inhibitory effect of sulfated galactans from the marine alga Bostrychia montagnei on herpes simplex virus replication in vitro.

Sulfated polysaccharides exhibit many biological properties such as antiviral and anticoagulant activities. Herein, we report the antiviral activity of sulfated galactans extracted from the red sea-weed Bostrychia montagnei against herpes simplex virus types 1 (strain F and the thymidine kinase-deficient strains Field and B2006) and 2 (strain G). Two crude extracts obtained with cold and hot water as well as some fractions obtained by anion exchange chromatography, inhibited significantly the replication of the different strains of herpesviruses as determined by plaque reduction assays. The inhibitory effect of the compounds studied here took place only when they were added during the adsorption period. They were found to be highly selective antiviral substances, causing no impairment of Vero cell viability. Furthermore, they had no direct inactivating effect on virions by incubation in a virucidal assay. The antiviral activity could be correlated with the molecular weight and sulfate content of the polysaccharides. Although sulfated polysaccharides are generally endowed with anticoagulant properties, the results of the activated partial thromboplastin time and the thrombine time assays indicated that the natural sulfated polysaccharides from Bostrychia montagnei have very low anticoagulant activity, confirming that there is no relation between the antiviral and anticoagulant properties.

Id2 is a retinoblastoma protein target and mediates signalling by Myc oncoproteins.

In mammalian cells, Id proteins coordinate proliferation and differentiation. Id2 is a dominant-negative antagonist of basic helix-loop-helix transcription factors and proteins of the retinoblastoma (Rb) family. Here we show that Id2-Rb double knockout embryos survive to term with minimal or no defects in neurogenesis and haematopoiesis, but they die at birth from severe reduction of muscle tissue. In neuroblastoma, an embryonal tumour derived from the neural crest, Id2 is overexpressed in cells carrying extra copies of the N-myc gene. In these cells, Id2 is in molar excess of the active form of Rb. The overexpression of Id2 results from transcriptional activation by oncoproteins of the Myc family. Cell-cycle progression induced by Myc oncoproteins requires inactivation of Rb by Id2. Thus, a dual connection links Id2 and Rb: during normal cell-cycle, Rb prohibits the action of Id2 on its natural targets, but oncogenic activation of the Myc-Id2 transcriptional pathway overrides the tumour-suppressor function of Rb.

Gemcitabine as second-line treatment for advanced non-small-cell lung cancer: A phase II trial.

PURPOSE: To investigate the activity and toxicity of gemcitabine as a single agent in patients with advanced non-small-cell lung cancer (NSCLC) after recurrence or failure of previous treatment with a platinum-containing regimen. PATIENTS AND METHODS: From November 1995 to October 1997, 83 patients with stage IIIB or IV NSCLC received gemcitabine 1,000 mg/m(2) once a week for 3 weeks every 28 days. Responses were assessed every two treatment courses. The median age of the patients was 63 years; Eastern Cooperative Oncology Group performance status was 0 to 1 in 62 patients and 2 in 21 patients. The predominant histology was squamous (39 patients); 49 patients had stage IV disease and 34 patients had stage III disease (33 stage IIIB and one stage IIIA). RESULTS: Sixteen patients (19%) achieved a partial response to treatment; the median duration of response was 29 weeks (range, 6 to 50 weeks). Treatment was well tolerated: grade 2 to 3 (World Health Organization standardized response criteria) leukopenia and thrombocytopenia occurred in 23% and 20% of patients, respectively. Mild asthenia was observed in 16% of patients, and peripheral edema in 5% of patients. Nausea and vomiting were present in 16% of patients. CONCLUSION: In this experience, gemcitabine showed significant activity without relevant toxicity, mainly in patients who were previously responsive to chemotherapy. This suggests a possible role for gemcitabine as a second-line treatment in patients who had a previous response or achieved stable disease with a platinum-containing regimen.

Gemcitabine as second-line treatment for relapsing or refractory advanced non-small cell lung cancer: a phase II trial.

We investigated the activity and toxicity of gemcitabine as a single agent in patients with advanced non-small cell lung cancer (NSCLC) after recurrence or failure of previous treatment with a platinum-containing regimen. From November 1995 to October 1997, 83 patients (73 men and 10 women) with stage IIIB or IV NSCLC received gemcitabine 1,000 mg/m2 on a weekly x 3 every 4 weeks schedule. Responses were assessed every two treatment courses. The median age of the patients was 63 years. Eastern Cooperative Oncology Group performance status was 0-1 in 62 patients; 2 in 21 patients. The predominant histology was squamous (39 patients); 49 patients had stage IV disease and 34 patients had stage III disease (33 stage IIIB and I stage IIIA). Sixteen patients (19%) achieved a partial response to treatment; the median duration of response was 29 weeks (range, 6 to 50 weeks). Treatment was well-tolerated: leukopenia and thrombocytopenia World Health Organization grade 2-3 occurred in 23% and 20% of patients, respectively. Mild asthenia was observed in 16% of patients and peripheral edema was observed in 5% of patients. Nausea and vomiting were present in 16% of patients. In this study, gemcitabine showed significant activity in a patient population usually associated with poor prognosis. This finding suggests a possible role for gemcitabine as second-line treatment in patients who have recurring disease or who have failed a platinum-containing regimen, and in the absence of significant toxicity.

Cisplatin-vindesine-mitomycin (MVP) vs cisplatin-ifosfamide-vinorelbine (PIN) vs carboplatin-vinorelbine (CaN) in patients with advanced non-small-cell lung cancer (NSCLC): a FONICAP randomized phase II study. Italian Lung Cancer Task Force (FONICAP).

In the present multicentre randomized phase II trial, the activity and toxicity of three platinum-based combination regimens for the treatment of advanced non-small-cell lung cancer (NSCLC) were evaluated. The three regimens were: MVP (mitomycin-C 6 mg m(-2) on day 1, vindesine 3 mg m(-2) on days 1 and 15, and cisplatin 80 mg m(-2) on day 1 every 28 days), PIN (cisplatin 80 mg m(-2) day 1, ifosfamide 3 g m(-2) day 1 and vinorelbine 25 mg m(-2) day 1 and 8 every 21 days) and CaN (carboplatin 350 mg m(-2) day 1 and vinorelbine 25 mg m(-2) days 1 and 8 every 28 days). A total of 140 chemotherapy-naive patients entered the study; 49 patients were treated with MVP, 48 with PIN and 43 with CaN. Sixty-seven per cent of the patients had stage IV disease. Response rates, calculated on an 'intention to treat' basis, were as follows: MVP, 14.3% (95% CI 5.94-27.2%); PIN, 16.7% (95% CI 7.4-30.2%); and CaN, 14% (95% CI 5.3-27.9%). The overall median survivals were 256, 269 and 243 days for patients treated with MVP, PIN and CaN respectively. Myelosuppression was the most frequent toxicity: grade 3-4 leucopenia was observed in 14.3%, 25% and 18.6% of patients treated with MVP, PIN and CaN respectively. This multicentre phase II randomized trial shows that MVP, PIN and CaN can be administered on an outpatient basis with acceptable toxicities. Unfortunately, the three regimens showed an activity significantly lower than that reported in previous single-institution phase II trials.

Antiherpetic and anticoagulant properties of carrageenans from the red seaweed Gigartina skottsbergii and their cyclized derivatives: correlation between structure and biological activity.

The antiviral activity against herpes simplex virus types 1 and 2 of kappa/l-, partially cyclized mu/v-, and lambda-carrageenans isolated from the red seaweed Gigartina skottsbergii and their cyclized derivatives was analyzed. lambda-Carrageenans and the partially cyclized mu/v-carrageenan were the most potent inhibitors of herpes viruses (including acyclovir-resistant variants and clinical isolates), with IC50 values lower than 1 microgram ml-1 against both serotypes and selectivity indices higher than 10(3). kappa/l-Carrageenans were slightly less effective than the other two types with IC50 values in the range 1.6-4.1 micrograms ml-1. Antiherpetic activity was directly correlated to the amount of alpha-D-galactose 2,6-disulfate residues in the natural carrageenans. The cyclization of the alpha-D-galactose 6-sulfate and 2,6-disulfate units into 3,6-anhydro-alpha-D-galactose and 3,6-anhydro-alpha-D-galactose 2-sulfate residues in these polysaccharides, in general, lowers the antiherpetic activity of the derivatives with respect to the natural carrageenans. Some carrageenans showed a very reduced anticoagulant activity only at concentrations that were considerably higher than the IC50, whereas others were totally devoid of anticoagulant properties. Among natural carrageenans, the mu/v-type IC3 shows the best relationship between antiviral efficacy and lack of anticoagulant action, resulting a very promising compound.

Room temperature, low-field 13C-n.m.r. spectra of degraded carrageenans: Part III. Autohydrolysis of a lambda carrageenan and of its alkali-treated derivative.

Autohydrolysis of lambda and theta carrageenans produces degraded products which are useful for 13C-n.m.r. spectroscopy, with low-field equipment and at room temperature. Data obtained from these spectra are doubly valuable as they are used for the structural study of parent carrageenans and to investigate the reactions carried out during autohydrolysis.

Phase II study of vinorelbine (Navelbine) in previously treated small cell lung cancer patients. EORTC Lung Cancer Cooperative Group.

26 previously treated patients with progressive recurrent small cell lung cancer (SCLC) were given vinorelbine (Navelbine), 30 mg/m2 weekly. All patients had responded to first-line chemotherapy and were off therapy for at least 3 months. Partial response was observed in 4 out of 25 eligible patients (16%; 95% confidence interval 4-36%), stable disease in 7 patients and progression in 12 patients. The limiting toxicity was a non-cumulative leucopenia (80%, 32% WHO grade 3-4). Reaction at the site of injection was observed in 5 patients, causing treatment discontinuation in 2 cases. Other non-haematological toxicities were moderate. These results suggest acceptable toxicity and some antitumour activity of vinorelbine in pretreated SCLC patients.