Glutamate and GABA in Microglia-Neuron Cross-Talk in Alzheimer’s Disease

The physiological balance between excitation and inhibition in the brain is significantly affected in Alzheimer’s disease (AD). Several neuroactive compounds and their signaling pathways through various types of receptors are crucial in brain homeostasis, among them glutamate and γ-aminobutyric acid (GABA). Activation of microglial receptors regulates the immunological response of these cells, which in AD could be neuroprotective or neurotoxic. The novel research approaches revealed the complexity of microglial function, including the interplay with other cells during neuroinflammation and in the AD brain. The purpose of this review is to describe the role of several proteins and multiple receptors on microglia and neurons, and their involvement in a communication network between cells that could lead to different metabolic loops and cell death/survival. Our review is focused on the role of glutamatergic, GABAergic signaling in microglia–neuronal cross-talk in AD and neuroinflammation. Moreover, the significance of AD-related neurotoxic proteins in glutamate/GABA-mediated dialogue between microglia and neurons was analyzed in search of novel targets in neuroprotection, and advanced pharmacological approaches.     

Nitric Oxide-Dependent Mechanisms Underlying MK-801- or Scopolamine-Induced Memory Dysfunction in Animals: Mechanistic Studies

MK-801, an NMDA receptor antagonist, and scopolamine, a cholinergic receptor blocker, are widely used as tool compounds to induce learning and memory deficits in animal models to study schizophrenia or Alzheimer-type dementia (AD), respectively. Memory impairments are observed after either acute or chronic administration of either compound. The present experiments were performed to study the nitric oxide (NO)-related mechanisms underlying memory dysfunction induced by acute or chronic (14 days) administration of MK-801 (0.3 mg/kg, i.p.) or scopolamine (1 mg/kg, i.p.). The levels of L-arginine and its derivatives, L-citrulline, L-glutamate, L-glutamine and L-ornithine, were measured. The expression of constitutive nitric oxide synthases (cNOS), dimethylaminohydrolase (DDAH1) and protein arginine N-methyltransferases (PMRTs) 1 and 5 was evaluated, and the impact of the studied tool compounds on cGMP production and NMDA receptors was measured. The studies were performed in both the cortex and hippocampus of mice. S-nitrosylation of selected proteins, such as GLT-1, APP and tau, was also investigated. Our results indicate that the availability of L-arginine decreased after chronic administration of MK-801 or scopolamine, as both the amino acid itself as well as its level in proportion to its derivatives (SDMA and NMMA) were decreased. Additionally, among all three methylamines, SDMA was the most abundant in the brain (~70%). Administration of either compound impaired eNOS-derived NO production, increasing the monomer levels, and had no significant impact on nNOS. Both compounds elevated DDAH1 expression, and slight decreases in PMRT1 and PMRT5 in the cortex after scopolamine (acute) and MK-801 (chronic) administration were observed in the PFC, respectively. Administration of MK-801 induced a decrease in the cGMP level in the hippocampus, accompanied by decreased NMDA expression, while increased cGMP production and decreased NMDA receptor expression were observed after scopolamine administration. Chronic MK-801 and scopolamine administration affected S-nitrosylation of GLT-1 transport protein. Our results indicate that the analyzed tool compounds used in pharmacological models of schizophrenia or AD induce changes in NO-related pathways in the brain structures involved in cognition. To some extent, the changes resemble those observed in human samples.     

Biocompatible Materials in Otorhinolaryngology and Their Antibacterial Properties

For decades, biomaterials have been commonly used in medicine for the replacement of human body tissue, precise drug-delivery systems, or as parts of medical devices that are essential for some treatment methods. Due to rapid progress in the field of new materials, updates on the state of knowledge about biomaterials are frequently needed. This article describes the clinical application of different types of biomaterials in the field of otorhinolaryngology, i.e., head and neck surgery, focusing on their antimicrobial properties. The variety of their applications includes cochlear implants, middle ear prostheses, voice prostheses, materials for osteosynthesis, and nasal packing after nasal/paranasal sinuses surgery. Ceramics, such as as hydroxyapatite, zirconia, or metals and metal alloys, still have applications in the head and neck region. Tissue engineering scaffolds and drug-eluting materials, such as polymers and polymer-based composites, are becoming more common. The restoration of life tissue and the ability to prevent microbial colonization should be taken into consideration when designing the materials to be used for implant production. The authors of this paper have reviewed publications available in PubMed from the last five years about the recent progress in this topic but also establish the state of knowledge of the most common application of biomaterials over the last few decades.     

Role of Distinct Macrophage Populations in the Development of Heart Failure in Macrophage Activation Syndrome

Macrophage activation syndrome (MAS) is one of the few entities in rheumatology with the potential to quickly cause multiple organ failure and loss of life, and as such, requires urgent clinical intervention. It has a broad symptomatology, depending on the organs it affects. One especially dangerous aspect of MAS’s course of illness is myocarditis leading to acute heart failure and possibly death. Research in recent years has proved that macrophages settled in different organs are not a homogenous group, with particular populations differing in both structure and function. Within the heart, we can determine two major groups, based on the presence of the C-C 2 chemokine receptor (CCR2): CCR2+ and CCR2−. There are a number of studies describing their function and the changes in the population makeup between normal conditions and different illnesses; however, to our knowledge, there has not been one touching on the matter of changes occurring in the populations of heart macrophages during MAS and their possible consequences. This review summarizes the most recent knowledge on heart macrophages, the influence of select cytokines (those particularly significant in the development of MAS) on their activity, and both the immediate and long-term consequences of changes in the makeup of specific macrophage populations—especially the loss of CCR2− cells that are responsible for regenerative processes, as well as the substitution of tissue macrophages by the highly proinflammatory CCR2+ macrophages originating from circulating monocytes. Understanding the significance of these processes may lead to new discoveries that could improve the therapeutic methods in the treatment of MAS.     

Phytopathogenic Cercosporoid Fungi—From Taxonomy to Modern Biochemistry and Molecular Biology

Phytopathogenic cercosporoid fungi have been investigated comprehensively due to their important role in causing plant diseases. A significant amount of research has been focused on the biology, morphology, systematics, and taxonomy of this group, with less of a focus on molecular or biochemical issues. Early and extensive research on these fungi focused on taxonomy and their classification based on in vivo features. Lately, investigations have mainly addressed a combination of characteristics such as morphological traits, host specificity, and molecular analyses initiated at the end of the 20th century. Some species that are important from an economic point of view have been more intensively investigated by means of genetic and biochemical methods to better understand the pathogenesis processes. Cercosporin, a photoactivated toxin playing an important role in Cercospora diseases, has been extensively studied. Understanding cercosporin toxicity in relation to reactive oxygen species (ROS) production facilitated the discovery and regulation of the cercosporin biosynthesis pathway, including the gene cluster encoding pathway enzymes. Furthermore, these fungi may be a source of other biotechnologically important compounds, e.g., industrially relevant enzymes. This paper reviews methods and important results of investigations of this group of fungi addressed at different levels over the years.     

Sorption of copper,zinc and cobalt by oat and oat products

We determined copper, zinc and cobalt sorption by oat and its products under variable pH conditions as well as the content of neutral dietary fiber (NDF) and its fractional composition. Adsorbents in a model sorption system were: oat, dehulled oat, oats bran and oats flakes. Three various buffers (pH 1.8, 6.6 and 8.7) were used as dispersing solutions. Results collected during this study indicate that copper, zinc and cobalt sorption is significantly affected by the type of cereal raw material. Zinc and copper ions are subjected to higher sorption than cobalt ions. Examined metal ions were subjected to high sorption under conditions corresponding to the duodenum environment (pH 8.7( regardless of the kind of adsorbent. A little lower sorption capacity is observed under conditions close to the neutral environment, while the lowest one is found in environment reflecting conditions of stomach juice (pH 1.8). Zinc ions are bound intensively by dehulled oat, while oats flakes bound mostly copper and cobalt, independently on environmental conditions. Contents of dietary fiber in oat, dehulled oat, oat bran and oat flakes were: 40.1, 19.3, 20.3 and 14.3%, respectively. The dominating fraction in all oat products was the fraction of hemicelluloses. The content of remaining fractions varies in dependence on the product.     

Epoxidation of chloromethylbutenes by t-butyl hydroperoxide

The epoxidation of chloromethylbutenes by t-butyl hydroperoxide in the presence of Mo(CO)₆ has been investigated. The influence of important parameters on hydroperoxide conversion, selectivity of transformation to epoxy compound in relation to hydroperoxide used, yield in relation to olefin introduced (response function) has been described by regression equations in the form of a second order polynomial. The optimum values of: temperature, olefin to hydroperoxide molar ratio, reaction time, molar ratio of Mo(CO)₆ catalyst to hydroperoxide, ensuring the maximum values of these functions, have been determined. ©1997 SCI     

The Phenoxyalkyltriazine Antagonists for 5-HT6 Receptor with Promising Procognitive and Pharmacokinetic Properties In Vivo in Search for a Novel Therapeutic Approach to Dementia Diseases

Among the serotonin receptors, one of the most recently discovered 5-HT₆ subtype is an important protein target and its ligands may play a key role in the innovative treatment of cognitive disorders. However, none of its selective ligands have reached the pharmaceutical market yet. Recently, a new chemical class of potent 5-HT₆ receptor agents, the 1,3,5-triazine-piperazine derivatives, has been synthesized. Three members, the ortho and meta dichloro- (1,2) and the unsubstituted phenyl (3) derivatives, proved to be of special interest due to their high affinities (1,2) and selectivity (3) toward 5-HT₆ receptor. Thus, a broader pharmacological profile for 1–3, including comprehensive screening of the receptor selectivity and drug-like parameters in vitro as well as both, pharmacokinetic and pharmacodynamic properties in vivo, have been investigated within this study. A comprehensive analysis of the obtained results indicated significant procognitive-like activity together with beneficial drug-likeness in vitro and pharmacokinetics in vivo profiles for both, (RS)-4-[1-(2,3-dichlorophenoxy)propyl]-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (2) and (RS)-4-(4-methylpiperazin-1-yl)-6-(1-phenoxypropyl)-1,3,5-triazin-2-amine (3), but insensibly predominant for compound 2. Nevertheless, both compounds (2 and 3) seem to be good Central Nervous System drug candidates in search for novel therapeutic approach to dementia diseases, based on the 5-HT₆ receptor target.     

Geoenergy in Poland

This paper presents the current state of geothermal energy production in Poland and its future development prospects. At present, there are four geothermal heating plants in Poland. In addition, warm water is used in seven spa towns in balneology as well as in seven thermal swimming pools for recreational purposes. There has recently been an increase in the number of installed heat pumps in Poland – reaching 10,000 in 2010. In the near future the development of geothermics in Poland is forecast to continue. The first power and heat geothermal plant is being built in Uniejów whilst in more than ten other towns special swimming pool complexes using geothermal warm water are being built or designed. In the coming years heat pumps will be installed in living and office buildings as well as in public use buildings (mostly in newly built ones). Moreover, in Poland it is planned to use heat pumps in order to recover waste heat from factories and power plants.