Nociceptors in cardiovascular functions: complex interplay as a result of cyclooxygenase inhibition

Prostaglandins (PGs) are requisite components of inflammatory pain as indicated by the efficacy of cyclooxygenase 1/2 (COX1/2) inhibitors. PGs do not activate nociceptive ion channels directly, but sensitize them by downstream mechanisms linked to G-protein coupled receptors. Antiinflammatory effects are purported to arise from inhibition of synthesis and/or release of proinflammatory agents. Release of these agents from peripheral and central terminals of sensory neurons modulates nociceptive input from the periphery and synaptic transmission at the first sensory synapse, respectively. Heart and blood vessels are densely innervated by sensory nerve endings that express chemo-, mechano-, and thermo-sensitive receptors. Activation of these receptors mediates synthesis and/or release of vasoactive agents by virtue of their Ca²⁺permeability. In this article, we discuss that inhibition of COX2 reduces PG synthesis and renders beneficial effects by preventing sensitization of nociceptors, but at the same time, it might contribute to deleterious cardiovascular effects by compromising the synthesis and/or release of vasoactive agents.     

Proteomics as a complementary tool for identifying unintended side effects occurring in transgenic maize seeds as a result of genetic modifications

To improve the probability of detecting unintended side effects during maize gene manipulations by bombardment, proteomics was used as an analytical tool complementary to the existing safety assessment techniques. Since seed proteome is highly dynamic, depending on the species variability and environmental influence, we analyzed the proteomic profiles of one transgenic maize variety (event MON 810) in two subsequent generations (T05 and T06) with their respective isogenic controls (WT05 and WT06). Thus, by comparing the proteomic profiles of WT05 with WT06 we could determine the environmental effects, while the comparison between WT06 and T06 seeds from plants grown under controlled conditions enabled us to investigate the effects of DNA manipulation. Finally, by comparison of T05 with T06 seed proteomes, it was possible to get some indications about similarities and differences between the adaptations of transgenic and isogenic plants to the same strictly controlled growth environment. Approximately 100 total proteins resulted differentially modulated in the expression level as a consequence of the environmental influence (WT06 vs WT05), whereas 43 proteins resulted up- or down-regulated in transgenic seeds with respect to their controls (T06 vs WT06), which could be specifically related to the insertion of a single gene into a maize genome by particle bombardment. Transgenic seeds responded differentially to the same environment as compared to their respective isogenic controls, as a result of the genome rearrangement derived from gene insertion. To conclude, an exhaustive differential proteomic analysis allows to determine similarities and differences between traditional food and new products (substantial equivalence), and a case-by-case assessment of the new food should be carried out in order to have a wide knowledge of its features.     

Inactivation of mitochondrial 2-oxoglutarate dehydrogenase complex as a result of phospholipid degradation induced by freeze-thawing

The inactivation of 2-oxoglutarate dehydrogenase complex by freeze-thawing was examined along with alterations of membrane phospholipids, in order to elucidate the mechanism of freezing injury in mitochondria.The dehydrogenase complex activity in slowly frozen and thawed mitochondria decreased to 70% as compared to intact mitochondria and further decreased during incubation. This inactivation during incubation was temperature dependent, i.e., at temperatures up to 25°C there was a slight decrease, while at higher temperatures there was a marked decrease in the dehydrogenase complex activity. Simultaneously, there was a significant accumulation of free fatty acids, generated from mitochondrial phospholipids, which inhibited 2-oxoglutarate dehydrogenase and subsequently enzyme complex activity. Oxoglutarate dehydrogenase activity in mitochondria was markedly inhibited by exogenous phospholipase A, and this inhibition was partially prevented with bovine serum albumin. Furthermore, when intrinsic phospholipase A was either inhibited or stimulated, there was a respective decrease or increase in the enzyme complex inactivation.The activity of the purified enzyme complex decreased slightly after slow freezing, but remained constant even when incubated at temperatures up to 32°C. However, the activity of this enzyme complex was markedly reduced when incubated either in the presence of venom phospholipase A or with exogenous fatty acid.The relationship between inactivation of the 2-oxoglutarate dehydrogenase complex, phospholipase A activation and production of free fatty acids in frozen and thawed mitochondria is discussed.     

Structuro-functional changes in the placenta as a result of exposure to atmospheric pollutants

Under the influence of atmospheric pollutions certain structural-functional changes take place in placenta: terminal villi per stipulated square unite, villi with desquamated epithelium, with dilated vessels, with deposition of fibrinoid masses, with plasmodial buds increase in number; section area occupied by epithelial layer decreases; RNA concentration and histoenzymatic activity change in the latter.     

The whole as a result of self-organization

On the basis of the experimental discovery of characteristic eigenfrequencies of the human body, the living organism is considered as a quantum system and a dissipative structure, the long-range coherence of which is provided by electromagnetic interaction.Among dissipative structures a special class is discerned for stable intact systems. Included along with living objects in this class are other fundamental structural material units with discrete characteristic frequencies of single-particle type (the nucleus, atom, molecule).     

Catalytic activity and the stability of horseradish peroxidase increase as a result of its incorporation into a polyelectrolyte complex with chitosan

The incorporation of horseradish peroxidase into polyelectrolyte complexes with chitosans of different molecular weights (MW 5–150 kDa) yielded highly active and stable enzyme preparations. As a result of the selection of optimal conditions for the formation of peroxidase-chitosan complexes, it was found that 0.1% chitosan with a MW of 10 kDa had the strongest activatory effect on peroxidase (activation degree, >70%) in the reaction of o-dianisidine oxidation by hydrogen peroxide. The complex formed by 0.001% chitosan with a molecular weight of 150 kDa was most stable: when immobilized on foamed polyurethane, it retained at least 50% of the initial activity for 550 days. The highest catalytic activity was exhibited in a 0.05 M phthalate buffer (pH 5.9–6.2) by the complex containing 0.006–0.009% chitosan in the indicator reaction. The activatory effect of the polysaccharide on the enzyme was determined by its influence on the binding and conversion of the reducting substrate peroxidase.     

Coexistence in the chemostat as a result of metabolic by-products

Classical chemostat models assume that competition is purely exploitative and mediated via a common, limiting and single resource. However, in laboratory experiments with pathogens related to the genetic disease Cystic Fibrosis, species specific properties of production, inhibition and consumption of a metabolic by-product, acetate, were found. These assumptions were implemented into a mathematical chemostat model which consists of four nonlinear ordinary differential equations describing two species competing for one limiting nutrient in an open system. We derive classical chemostat results and find that our basic model supports the competitive exclusion principle, the bistability of the system as well as stable coexistence. The analytical results are illustrated by numerical simulations performed with experimentally measured parameter values. As a variant of our basic model, mimicking testing of antibiotics for therapeutic treatments in mixed cultures instead of pure ones, we consider the introduction of a lethal inhibitor, which cannot be eliminated by one of the species and is selective for the stronger competitor. We discuss our theoretical results in relation to our experimental model system and find that simulations coincide with the qualitative behavior of the experimental result in the case where the metabolic by-product serves as a second carbon source for one of the species, but not the producer.     

Plant teratologies as a result of phytoplasma infections

The direct correlation between teratological cases and phytoplasma infections was ascertained in spontaneous and cultivated plant species. Plants, belonging to 31 species and 12 families, showing symptoms of growth abnormalities were collected and analysed. Attempted detection of Rhodococcus fascians by isolation, PCR indexing and 16S rRNA sequencing from fasciated tissues allowed to exclude its presence. Nested PCR by universal primers and 16S rRNA sequence analyses indicated the presence of phytoplasmas, belonging to six groups, in the 44% of symptomatic samples. Among the infected species, Austrocylindropuntia exaltata, Opuntia subulata, Euphorbia characias, Euphorbia dendroides, Euphorbia linifolia, Euphorbia myrsinites, Rumex buchephalophorus, Linaria multicaulis and Fedia cornucopiae represent new phytoplasma hosts world-wide. Moreover this is the first report of phytoplasma belonging to subgroup 16SrRNA II-I in Italy. These findings together with the known erratic distribution in plant tissues of these phloem-restricted prokaryotes indicate a close correlation between fasciation and similar growth disorders and phytoplasma infections.     

Clonal exhaustion as a result of immune deviation

An overwhelming virus infection that spreads within a few days throughout the host can cause deletion of the specific cytotoxic T lymphocytes (CTL). This phenomenon is known as ‘clonal exhaustion’. Current explanations for this phenomenon are ‘clonal’, and consider either the terminal differentiation of the virus-specific CTL to an effector phenotype, or the lack of help and antigen presentation for a specific CTL clone. The virus remains controlled by some other form of immunity in the exhausted state. Candidates are innate immunity (especially NK cells andmacrophages) and a T helper type 2 based immune response. Surprisingly, the role of this other form of immunity in causing exhaustion has been ignored so far. Developing a mathematical model, we here investigate the possibility that this inter-clonal immunity is responsible for exhaustion by down regulating the CTL response. The model is based on previously published exhaustion data for Lymphocytic choriomeningitis virus as an in vivo model. We demonstrate that several complicated experiments on clonal exhaustion are consistentwith inter-clonal regulation. By interpreting the available data with a mathematical model, we compare this novel mechanism with the mechanisms suggested previously.