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Human economic activities in the catchment directly or indirectly affect the formation and contemporary functioning of river channels. Mainly through changes in land cover in the catchment, hydrotechnical works carried out in river channels, and the increase in development in the valley floor, human influences the circulation of water and sediment within the slopes and fluvial systems. This is usually reflected in the variation of the morphodynamic structure of river channels. The research was carried out in the riverbed of the Ochotnica River (Western Polish Carpathians), which is a left tributary of the Dunajec River. To understand the contemporary structure of the riverbed, a geomorphological mapping of the riverbed and an inventory of hydrotechnical buildings were carried out in 2021. Erosion and accumulation forms were characterized, and the maximum diameter of the channel material was determined. The minimum and maximum water levels for the period 1984-2021 were also analyzed. The morphodynamic structure of the Ochotnica riverbed was compared with the results of the mapping, which was carried out in 1984 and 2001. An increase in the number of erosional forms and a decrease in the number of accumulation forms along the longitudinal profile of the riverbed were found. An analysis of changes in the land cover of the catchment based on archival and contemporary cartographic materials was also carried out. In the period 1930-2019, an increase in the proportion of forest area, and a decrease in the area of arable land and grassland was found. Also noticeable is an increase in the area occupied by buildings at the bottom of the main valley, and in the valleys of tributaries, increasing the share of a sealed area in the catchment. The results of the study documented the impact of land cover changes and hydrotechnical regulations on the diversification of the morphodynamic structure of the Ochotnica River channel, including the intensification of erosion processes.The research has been supported by a grant from the Faculty of Geography and Geology under the Strategic Programme Excellence Initiative at Jagiellonian University.

Objectives Recent years have brought new developments in interventional chronic pain management, namely regenerative orthopedics utilizing platelet-rich plasma (PRP) as well as further evolution of pulsed radiofrequency neuromodulation (PRF). Both methods have been used separately. Here, we investigated whether PRF may potentiate the activation of platelets in PRP samples when both these techniques are combined together in in vitro conditions. Materials and methods Studies were performed on concentrated PRP samples (PRPs) obtained from acid citrate dextrose-treated blood taken from 11 healthy volunteers. PRPs were divided into four groups: 1) nonactivated PRP; 2) thrombin-activated PRP as a positive control for maximal platelets activation; 3) PRF-treated PRP exposed for 20 min to PRF energy generated by neurotherm radio frequency generator at 500 kHz, with a voltage of 40 V and maximal temperature of 42°C; and 4) a combination of groups 2 and 3. Results PRF-induced platelet activation measured by platelet factor 4 (PF4) and ATP release from PRPs was significantly higher compared to nonactivated PRPs, and similar to PF4 and ATP release from thrombin-activated PRPs. Thrombin activation did not potentiate PF4 release in PRF samples and even reduced ATP level. Additionally, PRF neither induced any platelet membrane damage measured by lactic dehydrogenase release from PRP nor modified any platelets viability or metabolism measured by MTT. Conclusions We confirmed that PRF may activate PRP without additional platelet activators. So, a combination of both methods PRF and PRP application may provide a more effective opportunity for tissue regeneration in dentistry, surgery, dermatology, or in orthopedics.

In this study thin films based on hyaluronic acid (HA) with tannic acid (TA) were investigated in three different weight ratios (80HA/20TA, 50HA/50TA, 20HA/80TA) for potential medical applications. Surface free energy as well as its roughness, mechanical properties, water vapor permeability rate, and antioxidant activity were determined. Moreover, the compatibility with blood and osteoblast cells was investigated. The irritation effect for hyaluronic acid/tannic acid films by in vitro method was also considered. The results showed that the films have low surface free energy (54-42 mJ/m2), and rough surface (Ra 2.92-3.45 nm; Rq 3.84-4.21), and showed antioxidant activity (RSA 26% for 80HA/20TA; 93% for 20HA/80TA). All of the studied compositions of hyaluronic acid/tannic acid films are hemocompatible (hemolysis rate below 2%), however fully cytocompatible are only films based on 50HA/50TA. All films except 80HA/20TA showed appropriate mechanical properties in terms of potential implantation. All samples did not show the irritation effect during the studies using the reconstructed human epidermis.

Chronic hyperglycemia contributes to vascular complications in diabetes. Resveratrol exerts anti-diabetic and anti-platelet action. This study aimed to evaluate the effects of resveratrol on metabolism and the function of blood platelets under static and in in vitro flow conditions in patients with type 2 diabetes. Blood obtained from 8 healthy volunteers and 10 patients with type 2 diabetes was incubated with resveratrol and perfused over collagen-coated capillaries. Isolated blood platelets were incubated with resveratrol and activated by collagen to assess platelet function, metabolism, ATP release, TXA2 production, lipid peroxidation, and gluthatione content. In the type 2 diabetes group, plasma glucose and fructosamine concentrations were significantly higher than in the healthy group. In in vitro studies, collagen-induced thrombi formation in the blood of diabetic patients was 33% higher than in the healthy group. Resveratrol reduced thrombi by over 50% in the blood of healthy and diabetic patients. TXA2 production was 47% higher in diabetic platelets than in the healthy group. Resveratrol reduced TXA2 release by 38% in healthy platelets and by 79% in diabetic platelets. Resveratrol also reduced the activities of enzymes responsible for glycolysis and oxidative metabolism in the platelets of both groups. These data indicate that the resveratrol-induced inhibition of platelet metabolism and TXA2 release may lead to a reduction of platelet function and thrombus formation in patients with type 2 diabetes. Therefore, resveratrol may be beneficial to prevent vascular complications as a future complementary treatment in aspirin-resistant diabetic patients.

Reconstruction of fluvial style changes in the San River in the Subcarpathian Basins is based on geomorphological and sedimentological analyses. The time control of alluvial fills and temporal changes in the river channel are derived from radiocarbon and optically stimulated luminescence dating combined with independent pollen-based biochronostratigraphy. The results showed that the alluvial plain of the braided (BR) or braided-meandering (BR-M?) river was abandoned before 12,800 cal BP. Large meanders (LM) were cut off in the older part of the Younger Dryas (YD; ca. 12,600 cal BP), and in the younger part of this period (ca. 12,450 cal BP). The small meanders (SM) developed at the end of the YD and were abandoned at the onset of the Preboreal (PB; ca.11,550 cal BP). The erosion phase at the YD-PB transition, reported from many valleys in Central Europe, was not confirmed in the study area. The full cycle of San River channel transformation (BR (BR-M?) → LM → SM); was estimated to be approximately 1200 years. According to the palynological data, open pine forests with birch that survived from the end of the Allerød dominated the landscape of the river valley during the YD cooling and did not undergo major changes during the warming in the early PB. Therefore, we assume that the influence of vegetation changes in the San River channel pattern transformation was nonsignificant. The location of the studied palaeochannels in the floodbasin filled with silty clayey deposits may have influenced the formation of relatively narrow and deep channels, than that of much the wider and shallower meanders from the YD, situated several kilometres downstream of the surveyed sites.

Mild thiamine deficiency aggravates Zn accumulation in cholinergic neurons. It leads to the augmentation of Zn toxicity by its interaction with the enzymes of energy metabolism. Within this study, we tested the effect of Zn on microglial cells cultivated in a thiamine-deficient medium, containing 0.003 mmol/L of thiamine vs. 0.009 mmol/L in a control medium. In such conditions, a subtoxic 0.10 mmol/L Zn concentration caused non-significant alterations in the survival and energy metabolism of N9 microglial cells. Both activities of the tricarboxylic acid cycle and the acetyl-CoA level were not decreased in these culture conditions. Amprolium augmented thiamine pyrophosphate deficits in N9 cells. This led to an increase in the intracellular accumulation of free Zn and partially aggravated its toxicity. There was differential sensitivity of neuronal and glial cells to thiamine-deficiency–Zn-evoked toxicity. The co-culture of neuronal SN56 with microglial N9 cells reduced the thiamine-deficiency–Zn-evoked inhibition of acetyl-CoA metabolism and restored the viability of the former. The differential sensitivity of SN56 and N9 cells to borderline thiamine deficiency combined with marginal Zn excess may result from the strong inhibition of pyruvate dehydrogenase in neuronal cells and no inhibition of this enzyme in the glial ones. Therefore, ThDP supplementation can make any brain cell more resistant to Zn excess.

Brain pathologies evoked by thiamine deficiency can be aggravated by mild zinc excess. Cholinergic neurons are the most susceptible to such cytotoxic signals. Sub-toxic zinc excess aggravates the injury of neuronal SN56 cholinergic cells under mild thiamine deficiency. The excessive cell loss is caused by Zn interference with acetyl-CoA metabolism. The aim of this work was to investigate whether and how astroglial C6 cells alleviated the neurotoxicity of Zn to cultured SN56 cells in thiamine-deficient media. Low Zn concentrations did not affect astroglial C6 and primary glial cell viability in thiamine-deficient conditions. Additionally, parameters of energy metabolism were not significantly changed. Amprolium (a competitive inhibitor of thiamine uptake) augmented thiamine pyrophosphate deficits in cells, while co-treatment with Zn enhanced the toxic effect on acetyl-CoA metabolism. SN56 cholinergic neuronal cells were more susceptible to these combined insults than C6 and primary glial cells, which affected pyruvate dehydrogenase activity and the acetyl-CoA level. A co-culture of SN56 neurons with astroglial cells in thiamine-deficient medium eliminated Zn-evoked neuronal loss. These data indicate that astroglial cells protect neurons against Zn and thiamine deficiency neurotoxicity by preserving the acetyl-CoA level.

Objectives: Zinc excitotoxicity and thiamine pyrophosphate deficiency (TD) are known pathogenic signals contributing to mechanism of different encephalopathies through inhibition of enzymes respons...

The study presents the diversification of sediments deposited on log (LS), boulder (BS) and mixed-type (LBS) steps located in the channel of a stream in a small forest mountain catchment in the Polish Carpathians. The topic of sediment diversification in a stream channel is an important issue not only from the perspective of sediment transport process and shaping fluvial systems in forested catchments caused by woody or rock debris but also in the context of functioning of local ecosystems. We aimed to test the following hypothesis: the morphodynamic features of a stream channel and the type of steps therein significantly affect the diversification of the size and shape of mineral deposits and play an important role in the process of sediments transport and processing in the channels of small mountain streams. In order to verify the above hypothesis, sediments were sampled directly from the stream channel (Ch) in its longitudinal profile as well as upstream and downstream of steps (LS, BS and LBS) in the channel. The diversification of features of sediment grain size was analysed taking into account step type and sediment location in the longitudinal profile of the stream channel. The research was conducted separately for fine-grained sandstone (A) and coarse-grained sandstone (B). In addition, the basic sedimentological indicators and the shape parameter of the gravels, as described by the Zingg method, were determined. In order to determine the transport predisposition of the sediments in a specific load, an analysis of sediment distribution was performed on the C/M (C&mdash, first percentile and M&mdash, median) diagram. The PCA (Principal component analysis) analysis showed that the step type significantly affects the processing as well as the size and shape diversification of mineral deposits, which confirms our hypothesis. Therefore, this study is a contribution to the current knowledge on fluvial processes occurring in stream channels in small forest mountain catchments.

N-acetylaspartate is produced by neuronal aspartate N-acetyltransferase (NAT8L) from acetyl-CoA and aspartate. In cholinergic neurons, acetyl-CoA is also utilized in the mitochondrial tricarboxylic acid cycle and in acetylcholine production pathways. While aspartate has to be shared with the malate&ndash, aspartate shuttle, another mitochondrial machinery together with the tricarboxylic acid cycle supports the electron transport chain turnover. The main goal of this study was to establish the impact of toxic conditions on N-acetylaspartate production. SN56 cholinergic cells were exposed to either Zn2+ overload or Ca2+ homeostasis dysregulation and male adult Wistar rats&rsquo, brains were studied after 2 weeks of challenge with streptozotocin-induced hyperglycemia or daily theophylline treatment. Our results allow us to hypothesize that the cholinergic neurons from brain septum prioritized the acetylcholine over N-acetylaspartate production. This report provides the first direct evidence for Zn2+-dependent suppression of N-acetylaspartate synthesis leading to mitochondrial acetyl-CoA and aspartate shortages. Furthermore, Zn2+ is a direct concentration-dependent inhibitor of NAT8L activity, while Zn2+-triggered oxidative stress is unlikely to be significant in such suppression.

An investigation to determine the transition zone between the hillslope system and the fluvial system in connection with the degree of differentiation of sediment located upstream and downstream of log steps (LS) and boulder steps (BS) was undertaken in the channel of a stream located in a small mountain catchment area in the Silesian Beskidy Mts. (Polish Carpathians), a stream channel into which large wood was introduced artificially several years ago. Granulometric analyses of 41 samples taken from upstream (21) and downstream (20) of steps were performed to analyze the effectiveness of log steps and boulder steps in the differentiation of mineral sediment. It was demonstrated that log steps have a significant impact on the functioning of the channel by shaping its longitudinal profile and affecting the transport of mineral material, whereas boulder steps retain less sediment, showing the beneficial effects of artificial creation of log steps in mountain stream channels. Results of granulometric analyses suggested the location of the theoretical transition zone between the hillslope system and the fluvial system, suggesting the location and range of this zone in small mountain catchment areas can change depending on the intensity and range of slope processes in the longitudinal profile of the channel.

This study presents the sedimentological and pollen analysis, and radiocarbon dating of the palaeochannel fill deposits situated on the wide alluvial ridge on which 131 archaeological sites were discovered. The analyzed territory covers the right bank of the San river valley (in the area of the Leszno profile) with an area of 72.5 km2. Increase of fine-grain sand sediments, and the presence of redeposited fragments of clayey silts (soil aggregates) correlates well with the increase man’s activity in the 2nd and the 1st half of the 1 st millennia BC (the decline of the Mierzanowice culture, the Trzciniec culture, the Tarnobrzeg Lusatian culture) as well as in the 1st millennium AD (the Przeworsk culture and the early Medieval settlement) and with transformation of plant communities recorded in the palynological sequence. The layer of sediments at the depth of 85–69 cm with the highest proportion of the finest clay fraction may indicate the reduction of cultivation or abandonment of arable land (the pre-Roman (La Tène) period).

Hyperactivation of blood platelets is an essential factor in the pathomechanism of diabetes-evoked angiopathies. The aim of this work was to investigate whether blood platelets hyperactivation resulting from type 2 diabetic hyperglycaemia-increased pyruvate dehydrogenase complex activity and excessive acetyl-CoA accumulation may be brought to the normal range by the enzyme inhibitors. Platelets were isolated from the blood of 9 type 2 diabetic patients and 10 healthy donors. Effects of 3-bromopyruvate and 3-nitropropionate on pyruvate dehydrogenase complex (PDHC) and succinate dehydrogenase activities, as well as levels of acetyl-CoA, ATP, thiobarbituric acid reactive species and aggregation were assessed in non-activated and thrombin-activated platelets. In type 2 diabetic patients fasting plasma glucose and fructosamine levels were 61 and 64% higher, respectively, than in the healthy group (p

A new generation of oral anticoagulants, direct thrombin or activated factor X inhibitors gradually replaces the existing antithrombotic agents, administered parenterally (heparin) or orally (vitamin K antagonists). Currently, the most widely used class of direct oral anticoagulants (DOACs) are the direct thrombin inhibitor dabigatran and rivaroxaban, apixaban and edoxaban – Xa inhibitors. Although previous reports suggested that DOACs therapy does not require laboratory screening, recently the new indications for monitoring and the types of laboratory tests used in the evaluation of the effectiveness of treatment have been updated. To quantify the activity of direct thrombin inhibitors a dilute thrombin clotting time (dTT) or ecarin clotting time (ECT) is recommended. The effect of rivaroxaban and apixaban can be determined by anti-Xa activity assay when calibrated with a rivaroxaban and apixaban standard. Observed changes in routine coagulation tests such as activated partial thromboplastin time (APTT), and prothrombin time (PT), with varying degrees of severity, can only be an indicator of an additional screening, which is the emergency clinical interventions.

This article presents potential errors related to the construction of absolute chronologies for Late Glacial and Early Holocene sediments accumulated in oxbow lakes in Central Europe and their influence on palaeoecological reconstruction. Our study is based on two sediment cores: (i) from the San River (Stubno-Naklo site in south-eastern Poland; S-N) and (ii) from the Dniester River (Luka site in western Ukraine) valleys. Accelerator mass spectrometry (AMS) 14C dating was performed on terrestrial plant macrofossils from each site to produce Bayesian age–depth models and to calculate sedimentation rates (SRs). The SR in both sites was characterised by high variability reflecting the developmental stage of oxbow lake. The highest SR values (1.18–1.23 cm yr-1) were identified at the S-N site at the beginning of the Holocene (ca. 11,550–11,470 cal. BP) and related to enhanced overbank deposition. The lowest SR values (0.01–0.02 cm yr-1) were identified in the transitional layer between the Younger Dryas and the Preboreal chronozone (ca. 11,810–11,160 cal. BP) in the Luka profile; this may have been related to the sedimentary gap(s) caused by falls in the water table and/or temporary desiccation of the water body. Moreover, our study revealed the presence of three distinctly aged AMS 14C dates in the Younger Dryas section of the Luka profile. These radiocarbon inversions were completely undetected by pollen analysis, which indicated the domination of Pinus and Betula without any significant fluctuations throughout the entire subsection. The presence of such ‘cryptic’ insertions of older material could lead to erroneous palaeoenvironmental reconstruction. Similarly the S-N site revealed anomalously ‘aged’ dates which were also difficult to detect by pollen analysis.

The aim of this study was to determine the effect of HNSCC tumour treatment on systemic Th1 and Th2 cytokine levels and investigate correlations with clinicopathological parameters. IL2, IL4, IL5, IL6, IL8, IL10, IL13, GMCSF, IFNγ and TNFα were measured in the serum of 101 newly-presenting HNSCC patients (9 oral cavity, 27 oropharynx, 57 laryngopharynx, 1 sinonasal, 1 parotid and 6 unknown), prior to and following treatment, using a Quantibody® array based multiplex sandwich ELISA (Raybiotech). Data were analysed with respect to T stage, nodal status, age and sex of the patient as well as time between collection of pre- and post-treatment serum. A significant decrease in the levels of the Th2 cytokines IL4, IL5, IL6 and IL10 and the Th1 cytokines IL2 and IL8 was observed between the pre- and post-treatment serum samples. IL13 and TNFα were significantly higher in early stage (T1/T2) tumours compared with late stage (T3/T4) and this trend was maintained for nodal involvement. IL4 was higher in node positive patients compared with node negative, whereas the converse was true for IL2; IL4 was also higher in younger patients compared with the older age group. These results suggest that removal of HNSCC tumours from patients results in reduced circulating Th2 cytokines without a concurrent increase in Th1 cytokines, indicative of a partial rebalance of the Th1/Th2 system following treatment. Furthermore the cytokine profile may be influenced by the size and nodal involvement of the tumour.

Background: Excessive blood platelet activity contributes to vascular complications in diabetic persons. Increased acetyl-CoA in platelets from diabetic persons has been suggested to be a cause of this hyperactivity. We therefore investigated whether l-carnitine, which up-regulates metabolism of acetyl-CoA in muscles and brain, may affect platelet function in healthy and diabetic individuals.Methods: We obtained platelets from healthy and diabetic persons and measured acetyl-CoA concentrations, malonyl dialdehyde (MDA) synthesis, and platelet aggregation in the absence and presence of l-carnitine. Activities of selected enzymes involved in glucose and acetyl-CoA metabolism were also assessed.Results: Fasting glucose, fructosamine, and hemoglobin A1c were present in significantly higher amounts in the blood of diabetic patients than in healthy individuals. Activities of carnitine acetyltransferase, glucose-6-phosphate dehydrogenase, oxoglutarate dehydrogenase, and fatty acid synthase were 17%–62% higher in platelets from diabetic patients. Mitochondrial acetyl-CoA was increased by 98% in platelets from diabetic patients, MDA synthesis was increased by 73%, and platelet aggregation by 60%. l-Carnitine had no or only a slight effect on these indices in platelets from healthy individuals, but in platelets from diabetic patients, l-carnitine caused a 99% increase in acetyl-CoA in the cytoplasmic compartment along with increases in MDA synthesis and platelet aggregation.Conclusions: Excessive platelet activity in persons with diabetes may result from increased acetyl-CoA, which apparently increases synthesis of lipid activators of platelet function. l-Carnitine may aggravate platelet hyperactivity in diabetic persons by increasing the provision of surplus acetyl-CoA to the cytoplasmic compartment.

The nature of the tumour microenvironment immune response in head and neck cancer patients has an important role in tumour development and metastasis, but it is unknown if this differs between cancer subsites or whether it is related to the peripheral immune response.Immune cells (CD4, CD8, Foxp3) in head and neck squamous cell carcinoma tissue (HNSCC; n = 66), detected by immunohistochemistry, have been correlated with tumour subsite and immune cells in the peripheral circulation (CD4(+)CD25(High)Foxp3(+) Treg and CD4(+) T cells), identified using flow cytometry.Oropharyngeal tumours had a greater number of infiltrating immune cells in both tumour and stroma compared with other subsites, but no difference was observed in the circulating levels. Immune cells in the stroma were positively related to those in the tumour with consistently higher levels in stroma. A strong relationship was found between the number of CD4(+) and Foxp3(+) cells but not between the number of CD8(+) and Foxp3(+) cells in the tumour. The number of Foxp3(+) cells within the tumour was positively correlated with the percentage of circulating CD4(+)CD25(High) cells positive for Foxp3. Late stage laryngeal tumours showed a higher number of Foxp3(+) lymphocytes compared with early stage malignancies, and oropharyngeal tumours had more CD4(+) cells in node negative tumours compared with node positive ones.The level of immune cell infiltration in head and neck squamous cell carcinoma appears to be subsite dependent residing primarily in the stroma and is likely to be dependent on the peripheral immune response.

Increased activity of blood platelets contributes to vascular complications in patients with diabetes. The aim of this work was to investigate whether persisting hyperglycemia in diabetic patients generates excessive accumulation of ATP/ADP, which may underlie platelet hyperactivity. Platelet ATP and ADP levels, thiobarbituric acid–reactive species synthesis, and aggregation of platelets from patients with diabetes were 18–82% higher than in platelets from healthy participants. In patients with diabetes, platelet stimulation with thrombin caused about two times greater release of ATP and ADP than in the healthy group while decreasing intraplatelet nucleotide content to similar levels in both groups. This indicates that the increased content of adenylate nucleotides in the releasable pool in the platelets of diabetic patients does not affect their level in metabolic cytoplasmic/mitochondrial compartments. Significant correlations between platelet ATP levels and plasma fructosamine, as well as between platelet ATP/ADP and platelet activities, have been found in diabetic patients. In conclusion, chronic hyperglycemia-evoked elevations of ATP/ADP levels and release from blood platelets of patients with diabetes may be important factors underlying platelet hyperactivity in the course of the disease.

Diabetes is known to increase blood platelet activity. Activities of pyruvate dehydrogenase (PDH), adenosine triphosphate (ATP)-citrate lyase (ATPCL), acetyl-coenzyme A (acetyl-CoA) content, malonyl dialdehyde (MDA), synthesis, and platelet aggregation in resting conditions and after activation with thrombin were measured in diabetic subjects and in age- and sex-matched healthy subjects. Activities of ATPCL and PDH, acetyl-CoA content, and thrombin-evoked MDA synthesis as well as platelet aggregation in diabetes were 31%, 51%, 62%, 35%, and 21%, respectively, higher than in healthy subjects. In addition, activation of diabetic platelets caused 2 times greater release of acetyl-CoA from their mitochondria than in controls. Both 1.0 mmol/L (-)hydroxycitrate and 0.1 mmol/L SB-204490 decreased acetyl-CoA content in platelet cytoplasm along with suppression of MDA synthesis and platelet aggregation. These inhibitory effects were about 2 times greater in diabetic than in control platelets. The data presented indicate that the ATPCL pathway is operative in human platelets and may be responsible for provision of about 50% of acetyl units from their mitochondrial to cytoplasmic compartment. Increased acetyl-CoA synthesis in diabetic platelets may be the cause of their excessive activity in the course of the disease. ATPCL may be a target for its specific inhibitors as factors decreasing platelet activity.

A characteristic feature of several encephalopathies is preferential impairment of cholinergic neurons. Their particular susceptibility to cytotoxic insults may result from the fact that they utilise acetyl-CoA both for energy production and acetylcholine synthesis. In addition, phenotypic modifications of cholinergic neurons are likely to influence their susceptibility to specific harmful conditions. SN56 cholinergic cells were differentiated by the combination of dibutyryl cAMP and retinoic acid. Al and sodium nitroprusside (SNP, NO donor) exerted direct additive inhibitory effects on mitochondrial aconitase activity. However, NO, Al, or amyloid β (Aβ)(25–35) caused none or only slight changes of choline O -acetyl transferase (ChAT) and pyruvate dehydrogenase (PDH) activity and relatively small loss of non-differentiated cells (NCs). On the other hand, in differentiated cells (DCs) these neurotoxins brought about marked decreases of these enzyme activities along with greater than in non-differentiated ones increase of cell-death rate. Aβ(35–25) had no effect on these cell parameters. NO and other compounds aggravated detrimental effect of each other particularly in differentiated cells. Thus, differential vulnerability of brain cholinergic neurons to various degenerative signals may result from their phenotype-dependent ratios of acetylcholine to acetyl-CoA synthesising capacities.