Is the epithelium-derived inhibitory factor in guinea-pig trachea a prostanoid?

To examine further the possible prostanoid involvement in the influence of the epithelium on guinea-pig tracheal smooth muscle responsiveness, we have analyzed the effects of LTD4, methacholine and histamine on the level of airway smooth muscle tone and on the amounts of PGE2, PGF2 alpha and PGI2 (determined by radioimmunoassay) in the presence and absence of the epithelium. Removal of the epithelium increased the sensitivity of guinea-pig trachea to the contractile effects of LTD4, methacholine and histamine. LTD4 (3-100 nM), methacholine (0.1-10 microM) or histamine (0.3-30 microM) did not increase prostanoid release above control values in either the presence or absence of the epithelium. The unstimulated release of PGE2 and PGF2 alpha, but not PGI2, was decreased in tissues lacking epithelium. Indomethacin (1 microM) reduced the baseline tone to a smaller extent in the absence of epithelium. In the presence but not the absence of the epithelium, indomethacin increased the sensitivity of preparations to the contractile effect of methacholine. The results support the postulate of an epithelium-derived inhibitory factor modulating guinea-pig tracheal smooth muscle responsiveness. The identity of this factor is not known but is not PGI2 and is unlikely to be PGF2 alpha or PGE2. However, the possibility remains that the basal release of PGE2 and/or PGF2 alpha derived from the epithelium may markedly affect the responsiveness of guinea-pig tracheal smooth muscle. Furthermore, the epithelium is a significant source of PGE2 and PGF2 alpha which may be involved in the maintenance of baseline tone.     

Is macrophage migration inhibitory factor a therapeutic target in systemic lupus erythematosus?

Systemic lupus erythematosus (SLE) is the prototype of a cluster of diseases that are characterized by a loss of self tolerance and chronic inflammation in organs including skin, kidney, brain and joints. Researchers have long debated the varying contributions of the components of the immune system to the pathogenesis of SLE, but the emigration of leucocytes from the microcirculation, and the subsequent tissue inflammation mediated by these inflammatory cells, are key features of chronic inflammation seen in SLE. Macrophage migration inhibitory factor (MIF) is a broad-spectrum pro-inflammatory cytokine. We hypothesize that MIF is an important inflammatory mediator in the perpetuation of immune activation in SLE, via its effects on activation of T and B cells, and endothelial and effector cells. As MIF exerts anti-apoptotic effects, it may also play a role in promoting abnormal survival of autoreactive lymphocytes, thus perpetuating autoimmune reactivity. In addition, MIF has a unique relationship with glucocorticoids, in that MIF can override the effects of glucocorticoids and may be important in steroid resistance. By virtue of its pluripotent functions, we propose that MIF may be a critical mediator of inflammation and damage in SLE, and that targeting of MIF may offer therapeutic benefits in this disease.     

Is the salt marsh vegetation a determining factor in the sedimentation processes?

Many authors have referred to the important role of vegetation in the consolidation of salt marsh sediments, but experiments previously carried out by us have shown results that do not always agree with these statements. In other words, the type of salt marsh surface coverage is not the main factor that contributes to the consolidation of sediments. To test this hypothesis different Portuguese salt marsh stations (species/unvegetated areas) from two sites, Tagus estuary (Corroios and Pancas) and Ria de Aveiro (Barra and Verdemilho), were compared to evaluate their influence on suspended matter deposition on the salt marsh surface. A short-term sedimentation study was performed within stands of Spartina maritima, Halimione portulacoides, Sarcocornia perennis subsp. perennis and unvegetated areas, by analysing the deposition of sediment material on nylon filters anchored to the marsh surface. Numerical results obtained from hydrodynamic models coupled to a Lagrangean module implemented for the Ria de Aveiro and the Tagus Estuary, namely the root-mean square velocity (V _rms) and residual velocity of tides, were also used. Average sedimentation rates (mean value between the different surface cover in a salt marsh) showed a seasonal trend more or less defined but with significantly different values between sites and salt marshes. Sedimentation rates varied between marshes: there are significant differences between Pancas and the other three marshes, but only significant differences in sedimentation rates between Spartina and Sarcocornia. Despite the important role of vegetation in the consolidation of salt marsh sediments, our results suggest that, the position of stations and related abiotic conditions in the salt marshes are determining factors of variation to take into account in the studies related with the stabilization and survival of salt marshes facing sea level rise. Handling editor: P. Viaroli     

Is ammonia a pathogenetic factor in Alzheimer's disease?

An attempt was made to review experimental evidence in favor of the idea that ammonia plays a role in dementia of the Alzheimer type (DAT). Hyperammonemia causes biochemical and cellular dysfunctions in the brain, which can be found in brains of DAT patients. The most conspicuous among these findings are astrocytosis, impairment of glucose utilization, and a decreased rate of energy metabolism, and the impairment of neurotransmission, with a net increase in excitability and glutamate release. The derangement of lysosomal processing of proteins is another potential site of ammonia action. This aspect is especially important in view of the growing evidence for the role of the endosomal-lysosomal system in the formation of amyloidogenic fragments from -amyloid precursor protein. Ammonia is not considered a primary factor of the disease. However, since hyperammonemia and release of ammonia from the brains of DAT patients is well supported by published observations, ammonia should be taken into account as a factor that contributes to manifestations and the progression of DAT. If elevated ammonia concentrations turn out to be indeed as important in DAT, as is suggested in this review, rational therapeutic avenues can be envisaged that lead to the amelioration of symptoms and progression of the disease.Abbreviations -AP -amyloid protein - -APP -amyloid precursor protein - CNS central nervous system - DAT dementia of the Alzheimer type - GABA -aminobutyrate - MAO monoamine oxidase - NAD nicotinamide adenine dinucleotide This paper is dedicated to Rudi Vrba, a pioneer of the neurochemistry of ammonia, and a friend, at the occasion of his 68th birthday.     

Is the urokinase-type plasminogen activator system a reliable prognostic factor in gastric cancer?

AIM: The aim of this prospective study was to evaluate the clinical and prognostic impact of immunohistochemically assessed uPA and PAI-1 in patients with gastric cancer. METHODS: This prospective study analyzed specimens obtained from 105 gastric cancer patients who underwent gastrectomy with extended lymphadenectomy. The immunohistochemical expression of uPA and PAI-1 was studied semiquantitatively in the tumor epithelium and was correlated with the clinicopathological features of each patient. RESULTS: Univariate analysis revealed no statistically significant association of uPA levels with pT and pN category (p=0.655 and 0.053, respectively), grading (p=0.374), depth of tumor invasion (p=0.665), UICC classification (p=0.21) and the Laurén classification (p=0.578). PAI-1 expression showed no statistically significant correlation with pT, pN and M category (p=0.589, 0.414, and 0.167, respectively), grading (p=0.273), and the Laurén classification (p=0.368). Only the UICC classification was significantly correlated with PAI-1 (p=0.016). Kaplan-Meier analysis revealed no significant association of uPA and PAI-1 with overall survival (p=0.0929 and 0.0870, respectively). CONCLUSIONS: Our results could not verify any prognostic value of uPA and PAI-1 levels in patients with gastric carcinoma. Therefore, the uPA-system as a biologically defined prognostic marker to identify high-risk gastric cancers should be applied with caution. However, considering the number of patients involved and the borderline level of significance observed in this study, a larger number of events may have resulted in significant differences.     

Is progesterone a pre-hormone in the CNS?

In this paper, experimental evidences have been presented indicating that progesterone per se appears to be a powerful modulatory steroid of presynaptic striatal dopaminergic terminals of the central nervous system of the rat. This effect of the progesterone signal is concentration as well as infusion mode dependent. Low pulsatile doses of the steroid positively modulate the mechanism by which dopamine terminals respond to amphetamine stimulation and increase tissue dopamine concentration. Whereas, continuous and/or high doses of this steroid negatively modulate the response of the dopamine terminals to amphetamine stimulation and decreases tissue dopamine concentration. This effects occurs through a membrane mediated mechanism either upon the dopamine neuron directly and/or upon an interneuron. Pregnanolone a 5- beta-3 beta-metabolite of progesterone known to activate the hypothalamic LHRH neural apparatus at the level of the hypothalamus of ovariectomized estrogen primed rats in both in vitro as well as in vivo preparations was completely ineffective at the level of the corpus striatum of similar animal preparations. Therefore, it is reasonable to assume that site specific mechanisms exist within the central nervous system which may control differentially the final action of progesterone. In the hypothalamus, pregnanolone appears to be the final signal for its action on the LHRH neural apparatus, whereas in the corpus striatum, the steroid per se, and dependent on the modality and/or the strength of the signal can either directly or indirectly up-regulate (stimulatory component) or down-regulate (inhibitory component) the activity of striatal dopaminergic terminals.     

Human macrophage migration inhibitory factor: a proven immunomodulatory cytokine?

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory mediator with the ability to induce various immunomodulatory responses and override glucocorticoid-driven immunosuppression. Some of these functions have been linked to the unusual enzymatic properties of the protein, namely tautomerase and oxidoreductase activities. However, there are conflicting reports regarding the functional role of these enzymatic properties in normal physiological homeostasis and disease progression. Therefore, we have produced a highly pure, virtually endotoxin-free recombinant MIF preparation and fully characterized this using a variety of biochemical and biophysical approaches. The recombinant protein, with demonstrable enzymatic activity, was then used to systematically examine the biological activity of MIF. Surprisingly, treatment with MIF alone failed to induce cytokine expression, with the exception of IL-8. However, co-treatment of lipopolysaccharide (LPS) in conjunction with MIF produced synergistic secretion of tumor necrosis factor-alpha, interleukin (IL)-1, and IL-8 compared with LPS alone. The potentiating effect of MIF was seen at physiologically relevant concentrations. These data suggest that MIF has no conventional cytokine activity but, rather, acts to modulate and amplify the response to LPS.     

Is a compromised interferon response an etiologic factor in Reye's syndrome?

Young mice injected with sublethal doses of Toximul MP8, a typical commercial polyoxyethylene ether-based emulsifier, died more frequently when infected with encephalomyocarditis virus than did control mice. Lymphocytes taken from emulsifier-injected mice responded poorly to interferon induction, unlike lymphocytes from control animals. Interferon protected control mice against viral encephalomyocarditis, but such protection was not equally demonstrable in emulsifier-injected mice. These data suggest that the enhanced lethality of encephalomyocarditis virus in emulsifier-injected mice is associated with and perhaps caused by a compromised interferon response in these animals. Since these emulsifiers are commonly found in the environment in areas where forests are sprayed with pesticides, a group of children suffering from Reye''s syndrome who lived in such areas was investigated. Blood samples were obtained from five children with influenza B-associated Reye''s syndrome during their acute illness and during convalescence. Lymphocytes obtained from these samples and from peripheral blood samples from healthy children (controls) were induced to synthesize interferon by exposure to Newcastle disease virus. The lymphocytes from the convalescent patients and from the controls responded well to induction. However, the lymphocytes obtained from patients and from the controls responded well to induction. However, the lymphocytes obtained from patients during the acute phase of Reye''s syndrome responded very poorly and produced significantly less interferon.     

Is propagule size the critical factor in predicting introduction outcomes in passeriform birds?

Influential analyses of the propagule pressure hypothesis have been based on multiple bird species introduced to one region (e.g. New Zealand). These analyses implicitly assume that species-level and site-level characteristics are less important than the number of individuals released. In this study we compared records of passerine introductions with propagule size information across multiple regions (New Zealand, Australia, and North America). We excluded species introduced to just one of the three regions or with significant uncertainty in the historical record, as well as species that succeeded or failed in all regions. Because it is often impossible to attribute success to any single event or combination of events, our analysis compared randomly selected propagule sizes of unsuccessful introductions with those of successful introductions. Using Monte Carlo repeated sampling we found no statistical support for the propagule pressure hypothesis, even when using assumptions biased toward showing an effect.     

Benefits of aggregation in woodlice: a factor in the terrestrialization process?

In the animal kingdom, living in group is driven by a tradeoff between the costs and the benefits of this way of life. This review focuses especially on the benefits of aggregation and crowding in woodlice (Crustacea: Isopoda: Oniscidea). Indeed, woodlice are well known to live in groups. Their aggregation behavior, as described in the early works of Allee, is regarded as a mechanism to prevent desiccation to which woodlice are extremely sensitive. However, it is now clear that there are additional benefits to aggregation in woodlice. Hence, this review addresses not only the limitation of water loss as the main factor explaining aggregation patterns, but also alternative explanations as reduction of oxygen consumption, increase in body growth, biotic stimuli for reproduction, better access to mates, possible shared defenses against predators, promotion of coprophagy as a secondary food source, sheltering behavior and the acquisition of internal symbionts. In addition, we place woodlice in the context of a terrestrialization process and propose that woodlice—the only suborder of Crustacea almost entirely composed of strictly terrestrial species—are a model taxon for studying the evolution of sociality through the transition from water to land. Further, we discuss other ultimate causes of aggregation preserved in terrestrial isopods in light of those explained in aquatic isopods and under the concept of exaptation. This knowledge could help understand, in this and other taxa, how the spatial closeness between conspecifics may promote the colonization of new environments and nonphysiological responses to climatic constraints.     

Cobalamin neuropathy. Is S-adenosylhomocysteine toxicity a factor?

Cobalamin neuropathy was produced in cape fruit bats (Rousettus aegyptiacus) by a cobalamin-free diet combined with intermittent exposure to nitrous oxide, which inactivates cobalamin. There were no significant differences in S-adenosylmethionine/S-adenosylhomocysteine ratios in the central nervous system of cobalamin-deficient and cobalamin-replete bats. Taken with other data there are no grounds of support for a hypothesis that cobalamin neuropathy is the result of impaired methylation, however produced.     

Is sludge retention time a decisive factor for aerobic granulation in SBR?

This study investigated the role of sludge retention time (SRT) in aerobic granulation under negligible hydraulic selection pressure. Results showed that no successful aerobic granulation was observed at the studied SRTs in the range of 3-40 days. A comparison analysis revealed that hydraulic selection pressure in terms of the minimum settling velocity would be much more effective than SRT for enhancing heterotrophic aerobic granulation in sequencing batch reactor (SBR). It was shown that SRT would not be a decisive factor for aerobic granulation in SBR.