Catechol-o-methyltransferase inhibitor tolcapone improves learning and memory in naïve but not in haloperidol challenged rats

Objective(s): Dopamine plays an important role in cognitive functions. Inhibition of the dopamine-degrading enzyme catechol-O-methyltransferase (COMT) may have beneficial effects. Our aim was to assess the effect of COMT inhibitor tolcapone (TCP) on learning and memory in naïve and haloperidol-challenged rats.Materials and Methods: Male Wistar rats were divided into 9 groups (n=8):  naïve-saline, tolcapone 5; 15 and 30 mg/kg BW; haloperidol (HP) challenged-saline, haloperidol, haloperidol+tolcapone 5; 15 and 30 mg/kg BW. Two-way active avoidance test (TWAA), elevated T-maze, and activity cage were performed. Observed parameters were: number of conditioned responses (CR) and unconditioned responses (UCR), working memory index, and vertical and horizontal movements. Results: Naïve rats with 30 mg/kg BW TCP had a significantly increased number of CR  and  UCR during the long-term memory test. The animals with 5 mg/kg BW TCP significantly increased the number of UCR during the two retention tests. In haloperidol-challenged rats, the three experimental groups decreased the number of CR and UCR during the learning session and the two memory tests, compared to the saline group.  There was no significant difference between the HP-challenged rats treated with TCP and the haloperidol control group. All experimental naïve groups had significantly increased working memory index whereas none of the HP-challenged groups showed significant increase in this parameter. Conclusion: Our results demonstrate that in naïve rats tolcapone improves memory in the hippocampal-dependent TWAA task and spatial working memory in T-maze

Vitamin D3 exerts immunomodulatory and memory improving properties in rats with lipopolysaccharide-induced inflammation

Introduction: Vitamin D is a fat-soluble secosteroid, its primary function being regulation of calcium-phosphate homeostasis and maintenance of bone integrity and mineralization. Recently, pleotropic effects of this vitamin have been recognized, including an immunomodulatory role and involvement in normal brain development and functioning. Aim: The aim of the present study was to investigate the influence of cholecalciferol on serum inflammatory markers and memory functions in lipopolysaccharide (LPS) model of inflammation. Materials and methods: Male Wistar rats were randomly divided into 4 groups (n=8): control group, LPS control group, LPS + cholecalciferol (vitamin D3) 500 UI group, and 1000 IU/kg bw group. Step-down passive avoidance test, novel object recognition test (NORT), Y- and T-maze were performed to assess the memory functions. Latency, recognition index (RI), % spontaneous alteration (SA), and working memory index were registered. Tumor necrosis factor-alpha (TNF-α), IL-1β, transforming growth factor-β1 (TGF-β1), and brain derived neurotrophic factor (BDNF) serum levels were measured by ELISA. Results: LPS administration caused significant impairment in memory functions in all memory tasks. Cholecalciferol treatment caused significant increase in % SA, RI, and working memory index. In the step-down passive avoidance test, cholecalciferol-treated groups showed statistically significant increase in latency in the long-term memory test. Vitamin D3-treated rats showed decreased TNF-α and IL-1β serum levels whereas the concentration of TGF-β1 and BDNF increased. Conclusions: Cholecalciferol improves spatial working and episodic memory, which can at least partially be explained with its effect on systemic inflammatory response that is closely related with the development of neuroinflammation

Spatial distribution models and biodiversity of phytoplankton cysts in the Black Sea

The current study employed diverse statistical and machine learning techniques to investigate the biodiversity and spatial distribution of phytoplankton cysts in the Black Sea. The MaxEnt distribution modeling technique was used to forecast the habitat suitability for the cysts of three potentially toxic microalgal taxa (Lingulodinium polyedra, Polykrikos hartmannii, and Alexandrium spp.). The key variables controlling the habitat suitability of Alexandrium spp. and L. polyedra were nitrates and temperature, while for the P. hartmannii cysts, nitrates and salinity. The region with the highest likelihood of L. polyedra cyst occurrence appears to be in the western coastal and shelf waters, which coincides with the areas where L. polyedra red tides have been documented. The projected habitat suitability of the examined species partially overlapped, perhaps as a result of their cohabitation within the phytoplankton community and shared preferences for specific environmental conditions, demonstrating similar survival strategies. The north-western region of the Black Sea was found to be the most suitable environment for the studied potentially toxic species, presumably posing a greater risk for the onset of blooming events. Two distinct aspects of cysts’ ecology and settlement were observed: the dispersal of cysts concerns their movement within the water column from one place to another prior to settling, while habitat suitability pertains to the particular environment required for their survival, growth, and germination. Therefore, it is crucial to validate the model in order to accurately determine a suitable habitat as well as understand the transportation patterns linked to the particular hydrodynamic properties of the water column and the distinct features of the local environment

Analysis of finds (ingots and scrap) from the production centers near Nadarevo, Targovishte municipality

The present work aims to explain a part of the results of the elemental analysis of selected finds from the production center near Nadarevo, Targovishte municipality. Among them, finished products prevail, as well as raw materials. Mainly the latter refer to ingots and scrap metal reused for the production of new objects. The research was conducted at the Atomki Institute, Debrecen within the framework of IPERION-CH TNA Project (ACONOMAB) in 2018-2019. Proceeding to the essence of the topic, we should note that during the current second stage of the project, a total of 24 finds from the production center near Nadarevo were analyzed (Tab. I). Depending on the elemental composition of the base, the alloys from which the finds were cast are mainly: copper and lead alloys. The results of the research of the presented products and raw materials show that the non-ferrous metal entered the workshops of the production center near Nadarevo in the form of ingots, various scraps and old, out-of-use products. This includes both brass ingots and alloys with a predominance of brass, as well as "pure" copper, which was used as a basis for preparing the future alloy. Alloying additives, mainly lead and tin, were added to the “pure” metals, which contributed to improving the casting qualities of the alloy and obtaining quality castings with the desired appearance. Besides in the form of ingots, the metal in the workshops also came from scraps of non-ferrous metal - out-of-use products - ornaments, dishes, household items, etc. Thus, various raw materials enter the production centers: copper, brass, lead, tin-lead and lead-tin bronze. The frequency processing of the data from the analysis shows that tin and lead are predominantly used as alloying components to copper. Arsenic, antimony, silver and zinc do not play a leading role with the alloys in these cases. The insignificant concentrations of these elements give reason to consider them as natural impurities, and their distribution is a consequence of the extraction of metal from ores of different origin. Iron, which reaches several percent in copper, is also a natural impurity. In practice, in the production center near Nadarevo, alloys of non-ferrous metals of different composition and character were used, but preference was given to high-tin bronzes with the addition of lead

Analysis of Finds (Ingots and Scrap) from the Production Centers Near Zlatar, Preslav District and Novosel, Shumen District (Bulgaria) (part I)

Istoria cercetărilor metalurgiei a demonstrat faptul că determinarea caracterului aliajului pe baza elementelor chimice este o sarcină simplă în investigarea metalurgică istorică. Este greu de clarificat din ce depozit de minereu a fost extras metalul. Cuprul şi alte minereuri din fiecare zăcământ, pe lângă componenta principală cuprul, conţin şi multe alte elemente care formează o varietate de combinaţii calitative şi cantitative. Metalul extras din minereu dublează elementele care se află în el. Prin elementele care compun metalul, combinaţia generală a elementelor minereului poate fi stabilită cu suficientă acurateţe. Găsirea sursei materiei prime este mai importantă decât determinarea tipului de aliaj. Apoi, sunt dezvăluite rutele comerciale pe care metalul şi produsele sale au fost difuzate în diferitele comunităţi şi culturi. Astfel, se restabileşte relaţia dintre comunitatea metalurgiştilor, intermediari şi consumatorii produselor. Grupul de lingouri, ca una dintre principalele materii prime pentru producţie, precum şi produsele separate ca rebuturi, care se constituie în a doua materie primă importantă, reprezintă un subiect nu mai puţin interesant. Dimpotrivă, generează întrebări fundamentale cu privire la întregul proces de producţie, la etapele şi succesiunea proceselor sale. Printre principalele sarcini care pot fi rezolvate cu rezultatele cercetării compoziţiei elementare a întregului set de produse se numără originea metalului şi modalităţile de ajungere a acestuia în atelierele centrelor de producţie din vecinătatea oraşului Preslav. În plus, pot fi determinate principalele metale şi aliaje utilizate la fabricarea acestor produse, precum şi compoziţia şi principalele elemente de aliere din aliaj, care determină caracterul acestuia. Principalele rezultate oferă un punct de plecare pentru analiză în aceste direcţii, iar acumularea unei baze de date extinse va permite concluzii mai complete şi definitive. | Determining the character of the alloy based on the chemical elements is a simple task in historical metallurgical research. It is difficult to clarify from which ore deposit the metal was extracted. Copper and other ores from each deposit, in addition to the main component-copper, also contain many other elements that form a variety of qualitative and quantitative combinations. The metal extracted from the ore duplicates the elements that are in it. By the elements composing the metal, the general combination of the elements of the ore can be established with sufficient accuracy. Finding the source of the raw material is more important than determining the type of alloy. Then, the trade routes along which the metal and its products traveled in the different communities and cultures are revealed. Thus, the relationship between the community of metallurgists, middlemen and consumers of the product is restored. The group of ingots, as one of the main raw materials for production, as well as the products set aside for scrap, which is the second important raw material, is no less an interesting topic. On the contrary, it poses fundamental questions concerning the entire production process and its stages and sequence of processes. Among the main tasks that can be solved with the results of the research of the elemental composition of the entire set of products are the origin of the metal and the ways of its arrival in the workshops of the production centers in the vicinity of Preslav. In addition, the main metals and alloys used in the manufacture of these products can be determined, as well as its composition and the main alloying elements in the alloy, which determine its character, can be determined. The main results do provide a starting point for reasoning in these directions, and the accumulation of an extensive database will make the conclusions even more complete and definitive

PIXE – Analysis of Ingots and Srap from the Production Center Near Novosel, Shumen Region

In April 2018, a project called ACUDEMAB (Analyses of composition of non-ferrous metals, used for decorations in Early Middle Ages in Bulgaria) was successfully implemented in the Laboratory of Ion Beam Applications, MTA Atomki, Debrecen, in the framework of the EU H2020 IPERON CH (Integrated Project for the European Research Infrastructure ON Cultural Heritage) Trans-National Access program. Analysis of metal used for the casting of all these products, which is found in workshops and near furnaces can give convincing argument that this is precisely the metal used by medieval craftsmen. The results would give us the opportunity to identify ways of receipt of raw materials – import or reuse of waste products for new castings. The appearance of elements in the analysis depends on the geological and metallurgical conditions. According to the mineralogy of typical lead ores and the behaviour of the elements during the melting process, antimony Sb, arsenic As, bismuth Bi, copper Cu and silver Ag are among the leading elements in lead analysis. Similarly, with much less concentration than the actual melting of the ore, elements such as cobalt, iron, nickel and zinc, and gold, arsenic, selenium and tellurium may appear in the metal. Tin is not a typical ingredient for lead ores hence its absence in lead ingots. They belong to the so called Balkan metallogenic belt, where there are two basic types of mineralization: lead-zinc mineralization with key representatives of galenite, sphalerite, chalcopyrite, pyrite (there were some ancient galenite mines found) and gold bearing polymetal minerals, represented by galenite, sphalerite and gold-bearing pyrite. Gold is placed in the oxidising zone of the galenite and pyrite. Investigations made on the remains of antique copper mines make us say with great certainty that the major portion of raw materials (copper and bronze) came from the Burgas-Strandja mining region. Numerous traces of mining activities were found in that region. In the Burgas sub-region only there are more than 250 ancient ore mines

Pramipexole and tolcapone alleviate thermal and mechanical nociception in naive rats.

Introduction: Parkinson’s disease (PD) is а neurodegenerative disorder characterized mainly by its motor symptoms. The non-motor symptoms including pain are increasingly recognized in the last few decades. Existing evidence suggests that the dopaminergic neurotransmission has an essential role in pain control.Aim: The aim of the present study was to investigate the antinociceptive effect of dopaminergic drugs pramipexole and tolcapone against chemical and thermal stimuli in naive rats.Materials and methods: Male Wistar rats divided into 8 groups (n=8): saline; diclofenac 25 mg/kg body weight (bw) (positive control); pramipexole 0.5; 1 and 3 mg/kg bw; tolacapone 5; 15 and 30 mg/kg bw. Paw pressure and plantar tests were performed. Paw withdrawal pressure and latent time were measured. Statistical analysis was done by SPSS 19.Results: In the paw pressure test, pramipexole, in a dose of 1 and 3 mg/kg bw and tolcapone in a dose of 30 mg/kg bw, increased significantly the latency at 1, 2, and 3 hours compared to saline (p<0.05). In the plantar test, only the highest dose of pramipexole reached significance at 3 hours compared to the control rats (p<0.05). In contrast to pramipexole the three experimental groups with tolcapone markedly increased the latent time at 1 and 3 hours compared to saline (p<0.05).Conclusions: Pramipexole and tolcapone reduce mechanical and thermal nociception in naïve rats by enhancing dopaminergic neurotransmission at both spinal and supraspinal levels. In addition, tolcapone stimulates noradrenergic mediation which may contribute to its antinociceptive effect

An experimental study on phytochemical composition and memory enhancing effect of Ginkgo biloba seed extract

Introduction: The Ginkgo biloba L. tree is considered as one of the oldest species on Earth. It is known as a “living fossil” dating back approximately 200 million years. Both the leaves and seeds of this tree have been used for millennia in traditional Chinese medicine.Aim: To study the phytochemical profile of Gingko biloba seed extract (GBSE) and its memory enhancing effects.Materials and methods: Liquid chromatography with mass detection (LC-MS) was performed for phytochemical analyses of the extracts. For the in vivo experiments, male Wistar rats were divided randomly into 5 groups (n=8): saline; piracetam;  GBSE 50; 100, and 200 mg/kg b.w. Y-maze, T-maze, step-down passive avoidance and novel object recognition test (NORT) were performed. The observed parameters were: percentage of spontaneous alternations (% SA), working memory index, latency of reaction and recognition index, respectively. Statistical analysis was done using SPSS 19.Results: LC-MS analysis showed the presence of the flavonoids quercetin, kaempferol and isorhamnetin (as aglycones), the ginkgolides A, B, C, J, and bilobalide. In Y-maze task, the groups treated with 50 and 100 mg/kg of GBSE significantly increased the % SA during the memory test compared to saline (p<0.05). In T-maze test, the three experimental groups with GBSE significantly increased the working memory index in comparison with that of the control group (p<0.05). In step-down test, the animals receiving 100 mg/kg b.w. GBSE, notably increased the latency during both retention tests (p<0.05 and p<0.01, respectively). In NORT, only the animals with the middle dose of GBSE ameliorated the recognition index when compared to saline (p<0.05).Conclusions: GBSE enhances spatial working memory, recognition memory, and short- and long-term recall in naïve rats due to the synergic effects of detected flavonoids and terpene lactones on brain functions. The brain structures involved are probably the hippocampus and prefrontal cortex

Simulated microgravity affects carrageenan-induced inflammation process in rats

Weightlessness significantly impacts physiological systems. In the current study, we investigate the effects of 7 days exposure of rats to simulated microgravity (using a modified rat-modeled random positioning machine, working with four experimental animals simultaneously) on local carrageenan-induced inflammation and serum levels of liver enzymes, metabolites (glucose, urea, creatinine), and metabolic hormones (thyroid-stimulating hormone – TSH, aldosterone, cortisol). Male Wistar rats (n=12, m=200 ± 20 g) were evenly divided into RPM (experimental) and RPM-K (control) groups. The RPM rats showed a notable mass decrease compared to the controls. A significant increase in the carrageenan-induced inflammatory response was reached on the 24th hour in the RPM group compared to the RPM-K. Simulated microgravity resulted in lower serum glucose, creatinine, cortisol, and elevated urea levels. In conclusion, 7 days of exposure to random positioning machine-simulated microgravity promotes a pro-inflammatory state, potentially affecting insulin sensitivity, glucose utilization, and muscle catabolism

Immunomodulatory properties of cholecalciferol in rats with experimentally induced inflammation

The study aimed to investigate anti-inflammatory and immunomodulatory effects of cholecalciferol (vitamin D3) in rats with complete Freund’s adjuvant-induced arthritis (AIA) and lipopolysaccharide (LPS)-induced inflammation. In the first experiment, rats were treated with cholecalciferol 14 days before or from the day of induction of arthritis. In the second set-up, animals received cholecalciferol for 14 days which was followed by LPS injection. TNF (tumour necrosis factor)-alpha, IL (interleukin)-1β, TGF (transforming growth factor)-β1 levels were measured by enzyme linked immunosorbent assay (ELISA). Cholecalciferol treatment reduced paw oedema and ankle joint diameter in AIA. Significantly lower IL-1β concentrations were found in cholecalciferol-treated arthritic rats. In LPS-challenged rats, cholecalciferol markedly lowered serum TNF-α, whereas an elevation in IL-1β concentrations was observed. Cholecalciferol slightly increased TGF-β1 serum concentration in arthritic rats and non-significantly reduced its level in LPS-challenged animals. Our findings showed that cholecalciferol exerts immunomodulatory properties which probably contribute to its anti-inflammatory effect