Effect of pregabalin on contextual memory deficits and inflammatory state-related protein expression in streptozotocin-induced diabetic mice

Diabetes mellitus is a metabolic disease characterized by hyperglycemia due to defects in insulin secretion or its action. Complications from long-term diabetes consist of numerous biochemical, molecular, and functional tissue alterations, including inflammation, oxidative stress, and neuropathic pain. There is also a link between diabetes mellitus and vascular dementia or Alzheimer’s disease. Hence, it is important to treat diabetic complications using drugs which do not aggravate symptoms induced by the disease itself. Pregabalin is widely used for the treatment of diabetic neuropathic pain, but little is known about its impact on cognition or inflammation-related proteins in diabetic patients. Thus, this study aimed to evaluate the effect of intraperitoneal (ip) pregabalin on contextual memory and the expression of inflammatory state-related proteins in the brains of diabetic, streptozotocin (STZ)-treated mice. STZ (200 mg/kg, ip) was used to induce diabetes mellitus. To assess the impact of pregabalin (10 mg/kg) on contextual memory, a passive avoidance task was applied. Locomotor and exploratory activities in pregabalin-treated diabetic mice were assessed by using activity cages. Using Western blot analysis, the expression of cyclooxygenase-2 (COX-2), cytosolic prostaglandin E synthase (cPGES), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), nuclear factor-ĸB (NF-ĸB) p50 and p65, aryl hydrocarbon receptor (AhR), as well as glucose transporter type-4 (GLUT4) was assessed in mouse brains after pregabalin treatment. Pregabalin did not aggravate STZ-induced learning deficits in vivo or influence animals’ locomotor activity. We observed significantly lower expression of COX-2, cPGES, and NF-κB p50 subunit, and higher expression of AhR and Nrf2 in the brains of pregabalin-treated mice in comparison to STZ-treated controls, which suggested immunomodulatory and anti-inflammatory effects of pregabalin. Antioxidant properties of pregabalin in the brains of diabetic animals were also demonstrated. Pregabalin does not potentiate STZ-induced cognitive decline, and it has antioxidant, immunomodulatory, and anti-inflammatory properties in mice. These results confirm the validity of its use in diabetic patients. [Figure: see text

Resolvin D2 plays a protective role in RAW 264.7 Cells treated with polycyclic aromatic hydrocarbons

Eicosanoids are signaling molecules that control the immune processes and might have effects on inflammatory diseases. The aim of our study was to evaluate the effect of added resolvin D2 (RvD2), after treatment with polycyclic aromatic hydrocarbons (PAHs), on RAW 264.7 cells by using a UHPLC/MS-TOF method for the quantification of eicosanoids: 8-iPGF3α, PGF3α, 8-isoPGF2α, PGF2α and 5-iPF2α as well as cyclooxygenase 2 (COX-2), prostaglandin E synthase (cPGES) and prostaglandin F2α (FP) receptor protein expression by Western blot. The levels of PGF3α, PGF2α 8-iPGF3α 8-isoPGF2α and 5-iPF2α were decreased in RAW 264.7 cells after the exposure to PAHs and treatment with RvD2. It was observed that COX-2, cPGES and FP-receptor expression was decreased after co-treatment of the cells with PAHs and RvD2. Our findings suggest that RvD2 has anti-oxidant, anti-inflammatory and pro-resolving properties that may contribute significantly to alleviation of the harmful effects caused by PAHs in macrophages. Moreover, these results suggest that a diet rich in n-3 fatty acids might be helpful in resolving the inflammation and mitigating the effects of environmental stress in macrophages

Transportery gaba jako cel terapeutyczny dla nowych leków przeciwbólowych

ɣ-aminobutyric acid (GABA) is a widely distributed neurotransmitter in the mammalian central nervous system. Cortical GABA regulates a number of cognitive functions including attention, and working memory and is dysregulated in a number of psychiatric conditions like schizophrenia, insomnia, epilepsy and anxiety disorders. GABA-ergic neurotransmission disorders can exacerbate pain sensations. GABA is removed from the synaptic cleft by specific proteins called plasma membrane GABA transporters (GAT). Mechanisms through which the reported antinociceptive activity of GABA re-uptake inhibitors is mediated have not been defined. In the present work we focus on antinociceptive properties of new compounds which have the ability to inhibit the uptake of GABA and their use as potential drugs for the treatment of pain.Kwas ɣ-aminomasłowy (GABA) jest głównym neuroprzekaźnikiem hamującym w ośrodkowym układzie nerwowym (OUN). Bierze on udział w bardzo wielu procesach poznawczych, takich jak zdolność skupienia uwagi i pamięć robocza, natomiast zaburzenia jego przekaźnictwa odpowiadają prawdopodobnie za liczne schorzenia i choroby OUN, jak schizofrenia, bezsenność, padaczka i zaburzenia lękowe. Przekaźnictwo GABA-ergiczne odgrywa również ważną rolę w procesie czucia bólu. W transporcie GABA szczególną rolę odgrywają specyficzne białka (GAT), które poprzez wychwyt zwrotny z przestrzeni synaptycznej zmniejszają jego stężenie w szczelinie synaptycznej. Dokładny mechanizm inhibitorów GAT w modulacji czucia bólu nie został do tej pory poznany. W prezentowanej pracy skupiliśmy się na możliwości wykorzystanie inhibitorów GAT jako potencjalnych leków przeciwbólowych

GABA transporters as a therapeutic target for new analgesic drugs

Kwas ɣ-aminomasłowy (GABA) jest głównym neuroprzekaźnikiem hamującym w ośrodkowym układzie nerwowym (OUN). Bierze on udział w bardzo wielu procesach poznawczych, takich jak zdolność skupienia uwagi i pamięć robocza, natomiast zaburzenia jego przekaźnictwa odpowiadają prawdopodobnie za liczne schorzenia i choroby OUN, jak schizofrenia, bezsenność, padaczka i zaburzenia lękowe. Przekaźnictwo GABA-ergiczne odgrywa również ważną rolę w procesie czucia bólu. W transporcie GABA szczególną rolę odgrywają specyficzne białka (GAT), które poprzez wychwyt zwrotny z przestrzeni synaptycznej zmniejszają jego stężenie w szczelinie synaptycznej. Dokładny mechanizm inhibitorów GAT w modulacji czucia bólu nie został do tej pory poznany. W prezentowanej pracy skupiliśmy się na możliwości wykorzystanie inhibitorów GAT jako potencjalnych leków przeciwbólowych.ɣ-aminobutyric acid (GABA) is a widely distributed neurotransmitter in the mammalian central nervous system. Cortical GABA regulates a number of cognitive functions including attention, and working memory and is dysregulated in a number of psychiatric conditions like schizophrenia, insomnia, epilepsy and anxiety disorders. GABA-ergic neurotransmission disorders can exacerbate pain sensations. GABA is removed from the synaptic cleft by specific proteins called plasma membrane GABA transporters (GAT). Mechanisms through which the reported antinociceptive activity of GABA re-uptake inhibitors is mediated have not been defined. In the present work we focus on antinociceptive properties of new compounds which have the ability to inhibit the uptake of GABA and their use as potential drugs for the treatment of pain

ZASTOSOWANIE SULFONAMIDÓW W FARMAKOTERAPII CHORÓB ZAKAŹNYCH LUDZI I ZWIERZĄT ORAZ ZWIĄZANE Z TYM ZAGROŻENIA DLA ŚRODOWISKA

Sulfonamides are one of the oldest antibacterial drugs that remain still in use in humans and animals treatment. These compounds block the biosynthesis of folate in bacterial cells, thus inhibiting growth of bacteria. In order to potentiate the pharmacological activity, sulfonamides are often combined with trimethoprim. The role of those bacteriostatic agents has decreased over the years, mainly due to increasing bacterial resistance which is an effect of the inappropriate use of sulfonamides. There are still several compounds which are administered in humans to treat not only bacterial infections, but also protozoan ones (e.g. toxoplasmosis), for instance sulfamethoxazole, sulfacetamide, sulfathiazole. More number of sulfonamides is used in veterinary. According to this fact, there is a considerable adverse effect of those compounds on the environment: sulfonamides, after having been excreted from animal organisms, are present in soil and water, including groundwater. Hence there is a strong need to find effective methods of sulfonamides degradation in order to protect the environment

Using Canopy Height Model Obtained with Dense Image Matching of Archival Photogrammetric Datasets in Area Analysis of Secondary Succession

One of the threats that has a significant impact on the conservation status and on the preservation of non-forest Natura 2000 habitats, is secondary succession, which is currently analyzed using airborne laser scanning (ALS) data. However, learning about the dynamics of this phenomenon in the past is only possible by using archival aerial photographs, which are often the only source of information about the past state of land cover. Algorithms of dense image matching developed in the last decade have provided a new quality of digital surface modeling. The aim of this study was to determine the extent of trees and shrubs, using dense image matching of aerial images. As part of a comprehensive research study, the testing of two software programs with different settings of image matching was carried out. An important step in this investigation was the quality assessment of digital surface models (DSM), derived from point clouds based on reference data for individual trees growing singly and in groups with high canopy closure. It was found that the detection of single trees provided worse results. The final part of the experiment was testing the impact of the height threshold value in elevation models on the accuracy of determining the extent of the trees and shrubs. It was concluded that the best results were achieved for the threshold value of 1.25–1.75 m (depending on the analyzed archival photos) with 10 to 30% error rate in determining the trees and shrubs cover

The Efficacy Analysis of Determining the Wooded and Shrubbed Area Based on Archival Aerial Imagery Using Texture Analysis

Open areas, along with their non-forest vegetation, are often threatened by secondary succession, which causes deterioration of biodiversity and the habitat’s conservation status. The knowledge about characteristics and dynamics of the secondary succession process is very important in the context of management and proper planning of active protection of the Natura 2000 habitats. This paper presents research on the evaluation of the possibility of using selected methods of textural analysis to determine the spatial extent of trees and shrubs based on archival aerial photographs, and consequently on the investigation of the secondary succession process. The research was carried out on imagery from six different dates, from 1971 to 2015. The images differed from each other in spectral resolution (panchromatic, in natural colors, color infrared), in original spatial resolution, as well as in radiometric quality. Two methods of textural analysis were chosen for the analysis: Gray level co-occurrence matrix (GLCM) and granulometric analysis, in a number of variants, depending on the selected parameters of these transformations. The choice of methods has been challenged by their reliability and ease of implementation in practice. The accuracy assessment was carried out using the results of visual photo interpretation of orthophotomaps from particular years as reference data. As a result of the conducted analyses, significant efficacy of the analyzed methods has been proved, with granulometric analysis as the method of generally better suitability and greater stability. The obtained results show the impact of individual image features on the classification efficiency. They also show greater stability and reliability of texture analysis based on granulometric/morphological operations

HGF/SF increases number of skin melanocytes but does not alter quality or quantity of follicular melanogenesis.

Melanins are an important factor determining the vulnerability of mammalian skin to UV radiation and thus to UV-induced skin cancers. Transgenic mice overexpressing hepatocyte growth factor/scatter factor (HGF/SF) have extra-follicular dermal melanocytes, notably in the papillary upper dermis, and are susceptible to UV-induced melanoma. Pigmented HGF/SF neonatal mice are more susceptible than albino HGF/SF animals to UVA -induced melanoma, indicating an involvement of melanin in melanoma formation. This raises the question of the effect of transgenic HGF/SF on melanization. We developed a methodology to accurately quantitate both the production of melanin and the efficiency of melanogenesis in normal, and HGF/SF transgenic mice in vivo. Skin and hair shafts of 5 day old and adult (3 week old) C57BL/6-HGF/SF and corresponding C57BL/6 wild type mice were investigated by electron paramagnetic resonance spectroscopy (EPR) to quantitate melanin, by transmission electron microscopy (TEM) for the presence of melanosomes, and by standard histology and by Western blotting and zymography to determine the expression and activity of melanogenesis-related proteins. Eumelanin but no phaeomelanin was detected in transgenic C57BL/6-HGF and C57BL/6 wild type mice. Transgenic HGF/SF overexpression did not change the type of melanin produced in the skin or hair, did not affect the terminal content of melanin production in standard samples of hair and did not influence hair cycle/morphogenesis-related changes in skin thickness. No melanocytes were found in the epidermis and no melanosomes were found in epidermal keratinocytes. HGF/SF transgenic mice thus lack the epidermal melanin UV-protection found in constitutively dark human skin. We conclude that melanocytes in the HGF/SF transgenic mouse, particularly in the papillary dermis, are vulnerable to UVA which interacts with eumelanin but not phaeomelanin to induce melanoma