Gelidium commercial exploitation: natural resources and cultivation

The state of the Gelidium agarophyte resource was last reviewed in 1990 during the First International Workshop on Gelidium. The main objective of the present study was to gather and analyse the new information made available since then, with emphasis on the G. sesquipedale resource from the Iberian Peninsula and Morocco. Other Gelidium-based resources world-wide are also reviewed, as well as new attempts to cultivate Gelidium species in the sea. In general, since the late 1980s, G. sesquipedale yields have decreased in Portugal, and increased in Spain and Morocco. Current reported values, in dry weights, are ca. 670 t yr-1 for Portugal (average 1995–1997), 5200 t yr-1 in Spain, and 6950 t yr-1 for Morocco (average 1994–1996). Efforts to develop cultivation of G. sesquipedale in the sea in Spain have yet to progress beyond the demonstration scale. Other important Gelidium-based agarophyte resources are located in: (i) South Africa where, in addition to G. pristoides, new species are being harvested, with total agarophyte landings of 140 t yr-1 in 1996; (ii) Mexico, where G. robustum harvest averaged 750 t yr-1 in 1987–1996; (iii) and Chile where harvest of Gelidium species yielded ca. 460 t yr-1 in 1990–1992. Preliminary research on new techniques for commercial cultivation of Gelidium species is also reported from these countries. This revised version was published online in June 2006 with corrections to the Cover Date.     

Using zeta-potential measurements to quantify peptide partition to lipid membranes

Many cellular phenomena occur on the biomembranes. There are plenty of molecules (natural or xenobiotics) that interact directly or partially with the cell membrane. Biomolecules, such as several peptides (e.g., antimicrobial peptides) and proteins, exert their effects at the cell membrane level. This feature makes necessary investigating their interactions with lipids to clarify their mechanisms of action and side effects necessary. The determination of molecular lipid/water partition constants (K _p ) is frequently used to quantify the extension of the interaction. The determination of this parameter has been achieved by using different methodologies, such as UV-Vis absorption spectrophotometry, fluorescence spectroscopy and ζ-potential measurements. In this work, we derived and tested a mathematical model to determine the K _p from ζ-potential data. The values obtained with this method were compared with those obtained by fluorescence spectroscopy, which is a regular technique used to quantify the interaction of intrinsically fluorescent peptides with selected biomembrane model systems. Two antimicrobial peptides (BP100 and pepR) were evaluated by this new method. The results obtained by this new methodology show that ζ-potential is a powerful technique to quantify peptide/lipid interactions of a wide variety of charged molecules, overcoming some of the limitations inherent to other techniques, such as the need for fluorescent labeling.     

Genotoxicity of sodium metabisulfite in mouse tissues evaluated by the comet assay and the micronucleus test

Sodium metabisulfite (SMB, Na(2)S(2)O(5)) is widely used in the food and pharmaceutical industries, because of its ability to inhibit proliferation of microorganisms and its antioxidant properties. We have evaluated the genotoxic effects of SMB on different tissues of the mouse, by use of the comet assay (liver and blood cells) and the micronucleus test (blood and bone marrow cells). For all tissues, significant increases in damage index and damage frequency values were observed in the SMB-treated groups (1 and 2g/kg doses) compared to the control animals. The Kruskal-Wallis test showed that the mean micronucleus frequencies in peripheral blood and bone marrow cells of mice treated with the highest dose of SMB (2g/kg) showed significant increases, when compared with controls, and a significant reduction in the ratio of polychromatic to normochromatic erythrocytes was also seen. No difference in results between sexes was observed. Our results show that high oral doses of SMB may pose a genotoxic risk.     

Detection of human herpesvirus 7 infection in young children presenting with exanthema subitum

In this study, we assessed the prevalence of human herpesvirus-7 (HHV-7) in 141 serum samples from children less than four years of age with exanthematic disease. All samples were negative for measles, rubella, dengue fever and parvovirus B19 infection. Testing for the presence of human herpesvirus-6 (HHV-6)-specific high avidity IgG antibodies by indirect immunofluorescence assay (IFA) revealed two main groups: one composed of 57 patients with recent primary HHV-6 infection and another group of 68 patients showing signs of past HHV-6 infection. Another 16 samples had indeterminate primary HHV-6 infection, by both IgG IFA and IgM IFA. Serum samples were subjected to a nested polymerase chain reaction to detect the presence of HHV-7 DNA. Among patients with a recent primary HHV-6 infection, HHV-7 DNA was present in 1.7% of individuals; however, 5.8% of individuals tested positive for HHV-7 DNA in the group with past primary HHV-6 infection. Among the 16 samples with indeterminate diagnosis, 25% (4/16) had HHV-7 DNA (p < 0.002). We hypothesise that HHV-7 might be the agent that causes exanthema. However, a relationship between clinical manifestations and the detection of virus DNA does not always exist. Therefore, a careful interpretation is necessary to diagnose a primary infection or a virus-associated disease. In conclusion, we detected HHV-7 DNA in young children from the state of Rio de Janeiro, Brazil.     

Airflow pattern complexity and airway obstruction in asthma

The scientific and clinical value of a measure of complexity is potentially enormous because complexity appears to be lost in the presence of illness. The authors examined the effect of elevated airway obstruction on the complexity of the airflow (Q) pattern of asthmatic patients analyzing the airflow approximate entropy (ApEnQ). This study involved 11 healthy controls, 11 asthmatics with normal spirometric exams, and 40 asthmatics with mild (14), moderate (14), and severe (12) airway obstructions. A significant (P < 0.02) reduction in the ApEnQ was observed in the asthmatic patients. This reduction was significantly correlated with spirometric indexes of airway obstruction [FEV(1) (%): R = 0.31, P = 0.013] and the total respiratory impedance (R = -0.39; P < 0.002). These results are in close agreement with pathophysiological fundamentals and suggest that the airflow pattern becomes less complex in asthmatic patients, which may reduce the adaptability of the respiratory system to perform the exercise that is associated with daily life activities. This analysis was able to identify respiratory changes in patients with mild obstruction with an adequate accuracy (83%). Higher accuracies were obtained in patients with moderate and severe obstructions. The analysis of airflow pattern complexity by the ApEnQ was able to provide new information concerning the changes associated with asthma. In addition, this analysis was also able to contribute to the detection of the adverse effects of asthma. Because these measurements are easy to perform, such a technique may represent an alternative and/or a complement to other conventional exams to help the clinical evaluations of asthmatic patients.     

Mitochondrial energy metabolism in neurodegeneration associated with methylmalonic acidemia

Methylmalonic acidemia is one of the most prevalent inherited metabolic disorders involving neurological deficits. In vitro experiments, animal model studies and tissue analyses from human patients suggest extensive impairment of mitochondrial energy metabolism in this disease. This review summarizes changes in mitochondrial energy metabolism occurring in methylmalonic acidemia, focusing mainly on the effects of accumulated methylmalonic acid, and gives an overview of the results found in different experimental models. Overall, experiments to date suggest that mitochondrial impairment in this disease occurs through a combination of the inhibition of specific enzymes and transporters, limitation in the availability of substrates for mitochondrial metabolic pathways and oxidative damage.     

A series of mononuclear Co(III) complexes using tridentate N,O-donor ligands: chemical properties and cytotoxicity activity

Continuing our interest in tridentate ligands to develop new prototypes of cobalt-based metallodrugs for combating cancer, modifications in the backbone of HL1, [(2-hydroxybenzyl)(2-(pyridil-2-yl)ethyl]amine) were proposed in order to modulate the redox potential of new Co(III) complexes. Three ligands with electron withdrawing groups were synthesized: HL2: [(2-hydroxy-5-nitrobenzyl)(2-(pyridil-2-yl)ethyl]amine); HL3: [(2-hydroxybenzyl)(2-(pyridil-2-yl)ethyl]imine) and HL4: [(2-hydroxy-5-nitrobenzyl)(2-(pyridil-2-yl)ethyl]imine). They were used to obtain the respective mononuclear complexes 2, 3 and 4, which are discussed compared to the previous reported complex 1 (obtained from HL1). The new complexes were characterized and studied by several techniques including X-ray crystallography, elemental and conductimetric analysis, IR, UV-vis and ¹H NMR spectroscopies, and electrochemistry. The substitutions of the group in the para position of the phenol (HL1 and HL2) and the imine instead of the amine (HL3 and HL4), promote anodic shifts in the complexes reduction potentials. The influence of these substitutions in the biological activities of the Co(III) complexes against the murine melanoma cell line (B16F10) was also evaluated. Little effect was observed on cellular viability decrease for all free ligands, however the coordination to Co(III) enhances their activities in the following range: 1 > 4 ≈ 2 > 3. The data suggest that no straight correlation can be addressed between the reduction potential of the Co(III) center and the cell viability.     

Modelling foraging ants in a dynamic and confined environment

In social insects, the superposition of simple individual behavioral rules leads to the emergence of complex collective patterns and helps solve difficult problems inherent to surviving in hostile habitats. Modelling ant colony foraging reveals strategies arising from the insects’ self-organization and helps develop of new computational strategies in order to solve complex problems. This paper presents advances in modelling ants’ behavior when foraging in a confined and dynamic environment, based on experiments with the Argentine ant Linepithema humile in a relatively complex artificial network. We propose a model which overcomes the problem of stagnation observed in earlier models by taking into account additional biological aspects, by using non-linear functions for the deposit, perception and evaporation of pheromone, and by introducing new mechanisms to represent randomness and the exploratory behavior of the ants.     

Functional Identification of Cell Phenotypes Differentiating from Mice Retinal Neurospheres Using Single Cell Calcium Imaging

Degeneration of neural retina causes vision impairment and can lead to blindness. Neural stem and progenitor cells might be used as a tool directed to regenerative medicine of the retina. Here, we describe a novel platform for cell phenotype-specific drug discovery and screening of proneurogenic factors, able to boost differentiation of neural retinal progenitor cells. By using single cell calcium imaging (SCCI) and a rational-based stimulation protocol, a diversity of cells emerging from differentiated retinal neurosphere cultures were identified. Exposure of retinal progenitor cultures to KCl or to α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) stimulated Ca²⁺ transients in microtubule-associated protein 2 (MAP-2) positive neurons. Doublecortin (DCX) and polysialated neural cell adhesion molecule (PSA-NCAM) positive neuroblasts were distinguished from differentiated neurons on the basis of their response to muscimol. Ca²⁺ fluxes in glial fibrillary acidic protein (GFAP) or glutamine synthetase (GS) positive cells were induced by ATP. To validate the platform, neurospheres were treated with brain-derived neurotrophic factor (BDNF) (proneurogenic) or ciliary neurotrophic factor (CNTF) (gliogenic factor). BDNF increased the percentage of differentiated cells expressing Tuj-1 sensitive to KCl or AMPA and reduced the population of cells responding to muscimol. CNTF exposure resulted in a higher number of cells expressing GFAP responding to ATP. All together, our data may open new perspectives for cell type-specific discovery of drug targets and screening of novel proneurogenic factors to boost differentiation of neural retina cells to treat degenerative retinal diseases.     

Investigation on the pharmacological profile of antimony(III) complexes with hydroxyquinoline derivatives: anti-trypanosomal activity and cytotoxicity against human leukemia cell lines

Complexes [Sb(QN)₂Cl] (1), [Sb(QC)₂Cl] (2) and [Sb(QI)₂Cl] (3) were obtained with 8-hydroxyquinoline (HQN), 5-chloro-8-hydroxyquinoline (HQC) and 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol, HQI). The quinoline derivatives and their antimony(III) complexes were evaluated for their anti-trypanosomal activity as well as for their cytotoxicity against HL-60 and Jurkat human leukemia cell lines. Upon coordination to antimony(III) the anti-trypanosomal activity of HQC and HQI increases, the highest improvement being observed for complex (3), which was the most active among all studied compounds against both epimastigote and trypomastigote forms of Trypanosoma cruzi. All quinoline derivatives proved to be cytotoxic against both leukemia cell lineages. Upon coordination to antimony(III) the cytotoxicity of HQN improved against Jurkat leukemia cells. While SbCl₃ proved to be cytotoxic against HL-60 cells, it was not active against Jurkat cells. However, its coordination to the quinoline derivatives resulted in complexes with significant cytotoxicity against Jurkat cells.