Is platelet activating factor (PAF) an important mediator in bronchial asthma?

The development of selective PAF receptor antagonists may provide a novel approach to the treatment of human bronchial asthma. In preclinical animal models of human asthma, PAF receptor antagonists have been found to be efficacious in blocking antigen-induced changes in lung function. However, the majority of these models involve acute inflammatory events and transient changes in lung function and, therefore, their relevance to human asthma is questionable. In a recent study with a primate model of chronic airway inflammation and hyperresponsiveness, we have shown that treatment with a PAF receptor antagonist had no effect on reducing chronic inflammation and hyperresponsiveness. Similarly, recent studies in human asthmatics with PAF receptor antagonists have failed to show efficacy in blocking allergen-induced airway responses or to have any steroid sparing effects in patients with ongoing asthma. Thus, it seems that PAF may not be a key mediator which can be blocked and thereby provide therapy for bronchial asthma.     

Short-term variability of airway caliber-a marker of asthma?

Variability in airway caliber is a characteristic feature of asthma. Previous studies reported that the variability in respiratory system impedance (Zrs), measured by the forced oscillation technique during several minutes of tidal breathing, is increased in asthma and may be a marker of inherent instability of the airways. The aims of this study were to determine if short-term variability in impedance correlates with peak expiratory flow (PEF) variability or airway hyperresponsiveness (AHR). The SD of log-transformed impedance (lnZrsSD) was measured as a marker of short-term variability and compared with the diurnal variability of PEF over 2 wk in 28 asthmatic and 7 nonasthmatic subjects and with AHR to histamine in a cohort of 17 asthmatic and 82 nonasthmatic subjects. In addition, lnZrsSD was measured in eight nonasthmatic subjects before and after methacholine challenge in the upright and supine positions. There were no significant differences in lnZrsSD between asthmatic and nonasthmatic subjects (P = 0.68). Furthermore, in asthmatic subjects, lnZrsSD did not correlate with diurnal variability of PEF (rs = -0.12 P = 0.54) or with AHR to histamine (r = 0.10, P = 0.71). Neither methacholine challenge nor supine posture caused any significant change in lnZrsSD. We conclude that our findings do not support previous reports about the utility of short-term variability of impedance. Our findings suggest that, using standard methods for forced oscillometry, impedance variability does not provide clinically useful information about the severity of asthma.     

Activation of tumor necrosis factor receptor 1 in airway smooth muscle: a potential pathway that modulates bronchial hyper-responsiveness in asthma?

The cellular and molecular mechanisms that are involved in airway hyper-responsiveness are unclear. Current studies suggest that tumor necrosis factor (TNF)-α, a cytokine that is produced in considerable quantities in asthmatic airways, may potentially be involved in the development of bronchial hyper-responsiveness by directly altering the contractile properties of the airway smooth muscle (ASM). The underlying mechanisms are not known, but growing evidence now suggests that most of the biologic effects of TNF-α on ASM are mediated by the p55 receptor or tumor necrosis factor receptor (TNFR)1. In addition, activation of TNFR1 coupled to the tumor necrosis factor receptor-associated factor (TRAF)2-nuclear factor-κB (NF-κB) pathway alters calcium homeostasis in ASM, which appears to be a new potential mechanism underlying ASM hyper-responsiveness.     

Slow-reacting substance from alveolar macrophages--a mechanism of asthma?

The effects of alveolar macrophages on bronchial reactivity were studied in vitro to determine whether these cells could provide a pathogenetic link between cellular components of the inflammatory response, chemical medication of smooth muscle contraction and possible local mechanism of asthma. Alveolar macrophages harvested from rabbit lungs produced consistent and prolonged contractile responses in guinea-pig tracheal rings. The contractile material had the pharmacological and physical properties of slow-reacting substance (SRS) and, in particular, it was completely antagonized by minute concentrations (5 ng/ml) of a specific SRS antagonist, FPL 55712. The average contractile response per 10(6) macrophages was quantitatively equivalent to that produced by 76 ng methacholine. These findings not only support the view that local mechanisms may be of relevance in the pathogenesis of asthma, but could also have possible implications for therapy.     

Why is algaculture still incipient in Brazil?

Macroalgae represent 26 % of the global production of cultivated organisms, with Gracilaria spp. representing 12 % of that production; Eucheuma spp. and Kappaphycus alvarezii account for 34 % of world’s algae production. Despite the potential for cultivating seaweed in Brazil, and with its more than 8000 km of coastline, there is neither marine algaculture nor detailed knowledge even among aquaculture farmers concerning the utility of algae in agriculture, industry, and gastronomy, with the result that algaculture represents only the smallest fraction of national aquaculture production. The main cultivated species of seaweed sold in Brazil include the exotic K. alvarezii and native species of Gracilaria that are grown on small scales and do not meet national industrial demands, which must be supplemented by imports. We discuss Brazilian algaculture here, pointing out some of the problems that restrict commercial production of algae in that country and offer solutions that could be shared with other nations.     

Increased levels of albumin in bronchial washing fluid of patients with bronchial carcinoma. Could albumin be considered as a tumor marker?

BACKGROUND: The aim of this study was to evaluate the significance of albumin in bronchial washing fluid (BWF) and its relationship to three tumor markers (CEA, CA 19-9 and NSE). METHODS: Serum and BWF samples were collected in a group of 60 patients. Albumin and tumor markers in the BWF and serum of three groups: a control group (CG), a chronic bronchitis group (CBG) and a lung cancer group (CaG), were analyzed in a prospective cross-sectional study. The diagnostic yields of the tests in each environment (serum and BWF) were evaluated by using as cutoff points the values of the corresponding 90th percentile of CG and CBG taken together. RESULTS: A significant difference in albumin level (p < 0.001) was noted in the BWF of patients with cancer compared with the other two groups. In addition, a significant difference in CEA level (p < 0.001) was observed in the serum of cancer patients compared with the other two groups. The cutoff values for CEA in serum and albumin in BWF were 2.20 ng/mL and 2.00 g/dL, respectively. The areas under the corresponding ROC curves were 93% and 97%. Combination of CEA-serum and albumin-BWF by logistic regression analysis increased their diagnostic value. CONCLUSION: Measurement of albumin levels in BWF could be a useful additional diagnostic tool to differentiate malignant from non-malignant lung diseases. Moreover, the combined measurement of CEA in serum and albumin in BWF could be of aid in the follow-up of lung cancer patients.     

Are prions a relic of an early stage of peptide evolution?

The rather unique properties of prions and their presence in very different kinds of living species suggest that this type of molecule was created at a very early stage of evolution and may even represent a relic from a time where peptide evolution was ongoing and RNA/DNA did not yet exist. A comparison of the most frequently occurring amino acid sequences in known prions with the sequences preferentially formed in the salt-induced peptide formation reaction, the most simple mechanism enabling the formation of peptides under primitive earth conditions, shows a remarkable coincidence that strongly supports this hypothesis.     

Contingency Table Browser ? prediction of early stage protein structure

The Early Stage (ES) intermediate represents the starting structure in protein folding simulations based on the Fuzzy Oil Drop (FOD) model. The accuracy of FOD predictions is greatly dependent on the accuracy of the chosen intermediate. A suitable intermediate can be constructed using the sequence-structure relationship information contained in the so-called contingency table − this table expresses the likelihood of encountering various structural motifs for each tetrapeptide fragment in the amino acid sequence. The limited accuracy with which such structures could previously be predicted provided the motivation for a more indepth study of the contingency table itself. The Contingency Table Browser is a tool which can visualize, search and analyze the table. Our work presents possible applications of Contingency Table Browser, among them − analysis of specific protein sequences from the point of view of their structural ambiguity.     

Parapatric divergence of sympatric morphs in a salamander: incipient speciation on Long Island?

Speciation is often categorized based on geographic modes (allopatric, parapatric or sympatric). Although it is widely accepted that species can arise in allopatry and then later become sympatrically or parapatrically distributed, patterns in the opposite direction are also theoretically possible (e.g. sympatric lineages or ecotypes becoming parapatric), but such patterns have not been shown at a macrogeographic scale. Here, we analyse genetic, climatic, ecological and morphological data and show that two typically sympatric colour morphs of the salamander Plethodon cinereus (redback and leadback) appear to have become parapatrically distributed on Long Island, New York, with pure‐redback populations in the west and pure‐leadback populations in the east (and polymorphic populations in between and on the mainland). In addition, the pure‐leadback populations in eastern Long Island are genetically, ecologically and morphologically divergent from both mainland and other Long Island populations, suggesting the possibility of incipient speciation. This parapatric separation seems to be related to the different ecological preferences of the two morphs, preferences which are present on the mainland and across Long Island. These results potentially support the idea that spatial segregation of sympatric ecotypes may sometimes play an important part in parapatric speciation.     

Posthemorrhagic antipyresis: what stage of fever genesis is affected?

Romanovsky, Andrej A., and Yelena K. Karman.Posthemorrhagic antipyresis: what stage of fever genesis isaffected? J. Appl. Physiol. 83(2):359-365, 1997.It has been shown that hemorrhage leads to adecreased thermal responsiveness to lipopolysaccharide (LPS). The aimof this study was to clarify what stage of fever genesis[production of endogenous pyrogens such as interleukin-1 (IL-1),increase of the prostaglandin E₂(PGE₂) concentration in braintissue, activation of cold-defense effectors] is deficient inposthemorrhagic antipyresis. In adult rabbits, we evaluated the effectof acute hemorrhage (15 ml/kg) on the rectal temperature (T_re) responses to LPS fromSalmonella typhi (200 ng/kg iv),ethanol-purified preparation of homologous IL-1 (1 ml from 3.5 × 10⁷ cells, 1.5 ml/kg iv), andPGE₂ (1 µg,intracisternal injection). The effect of hemorrhage onT_re was also studied in afebrilerabbits, both at thermoneutrality (23°C) and during ramp cooling(to 7°C). The hemorrhage strongly attenuated the biphasicLPS-induced fever (a T_re rise of0.4 ± 0.1 instead of 1.2 ± 0.2°C at the time of the secondpeak), the monophasic T_re responseto IL-1 (by ~0.5°C for over 1-5 h postinjection), and thePGE₂-induced hyperthermia (0.4 ± 0.1 vs. 0.9 ± 0.1°C, maxima). In afebrileanimals, the hemorrhage neither affectedT_re at thermoneutrality norchanged the T_re response to coldexposure. The data suggest that neither insufficiency of cold-defenseeffectors nor lack of endogenous mediators of fever (IL-1,PGE₂) can be the only or eventhe major cause of posthemorrhagic antipyresis. Wespeculate that fever genesis is altered at a stage occurring after theintrabrain PGE₂ level is increasedbut before thermoeffectors are activated.

     

Conservation of the segmented germband stage: robustness or pleiotropy?

Gene expression patterns of the segment polarity genes in the extended and segmented germband stage are remarkably conserved among insects. To explain the conservation of these stages, two hypotheses have been proposed. One hypothesis states that the conservation reflects a high interactivity between modules, so that mutations would have several pleiotropic effects in other parts of the body, resulting in stabilizing selection against mutational variation. The other hypothesis states that the conservation is caused by robustness of the segment polarity network against mutational changes. When evaluating the empirical evidence for these hypotheses, we found strong support for pleiotropy and little evidence supporting robustness of the segment polarity network. This points to a key role for stabilizing selection in the conservation of these stages. Finally, we discuss the implications for robustness of organizers and long-term conservation in general.     

The association between IFN-γ and IL-4 genetic polymorphisms and childhood susceptibility to bronchial asthma

The present study aims to investigate the association between the genetic polymorphisms of interferon (IFN)-γ and interleukin (IL)-4 with childhood susceptibility to asthma and the levels of IFN-γ, IL-4, and immunoglobulin (Ig) E among asthmatic children. A total of 100 asthmatic children and 122 control children were enrolled in the present study. The genotypes of the IFN-γ gene at the − 179G/T locus and the IL-4 gene at the − 33C/T and − 589C/T loci were detected using polymerase chain reaction with restriction fragment length polymorphism. The IFN-γ gene at the + 874A/T locus and the IFN-γ CA repeats were tested using allele-specific and capillary electrophoresis, respectively, whereas the IFN-γ, IL-4, and total IgE levels were measured using enzyme-linked immunosorbent assays. The 100 asthmatic children and the 122 control children were all GG homozygous in the − 179 locus of the IFN-γ gene, which shows that the IFN-γ gene is not mutated at the − 179 locus. No significant differences were found in terms of genotypic and allelic frequency distribution in the IFN-γ gene or the CA repeat at the + 874A/T locus between the asthmatic children and the control (P > 0.05). An association was found between the polymorphism of the IFN-γ gene at + 874A/T and IFN-γ levels. IFN-γ expression was lower among patients with the AA genotype than those with the AT genotype (P < 0.05); the genotypic and allelic frequency distributions of the IL-4 gene at − 33C/T and − 589C/T were significantly different between the asthmatic children and the control (P < 0.05). The levels of IL-4 and IgE among children with TT genotype at the − 33 and − 589 loci were higher than those with the CT genotype, but only the polymorphism at − 33C/T was associated with IL-4 levels (P < 0.05). The polymorphisms of the IFN-γ gene at + 874A/T or the CA repeats are not correlated with susceptibility to asthma. Thus, the polymorphism at + 874A/T is correlated with IFN-γ level. The TT genotypes of the IL-4 gene at the − 33 and − 589 loci are associated with asthma susceptibility in children, and polymorphism at the − 33 locus may be associated with IL-4 level.     

Can biofuels finally take center stage?

Today, ethanol and biodiesel are predominantly produced from corn kernels, sugarcane or soybean oil. But researchers and investors are increasingly upbeat about another biofuel feedstock, lignocellulose--the most abundant biological material on earth.     

Persistent mucus accumulation: a consequence of delayed bronchial mucous cell apoptosis in RAO-affected horses?

This study examined the contribution of delayed apoptosis of bronchial mucous cells to mucus accumulation in equine recurrent airway obstruction (RAO). In pilot studies, Bcl-2, an apoptosis inhibitor, was detected in airway mucous cells of RAO-affected horses in remission and during acute disease, when most mucus was secreted. To study whether delayed apoptosis results in an increase in the number of mucous cells during disease recovery, six RAO-affected and six control horses were fed hay for 5 days to induce inflammation and then pellets for 7 days to partially resolve RAO before euthanasia. RAO-affected horses had more airway obstruction and luminal mucus than control horses under both management systems. At the time of euthanasia, RAO-affected horses had more inflammation and Bcl-2-positive bronchial mucous cells than control animals. In horses with >10 and <10 neutrophils per microliter of bronchoalveolar lavage fluid, >50% and <10% of mucous cells stained positive for Bcl-2, respectively. No differences in mucous cell number or amount of stored mucosubstance were observed between RAO-affected and control horses, but in RAO-affected animals, the amount of stored mucosubstance decreased as the number of neutrophils in bronchoalveolar lavage fluid increased. Because the number of mucous cells was similar in both groups of horses but only mucous cells of RAO-affected horses expressed Bcl-2 during recovery from acute disease, a conclusive role for Bcl-2 in prolonging bronchial mucous cell life could not be determined. Future studies are needed to compare horses that are kept in remission for prolonged periods when all mucous cells are fully developed.