Intrinsically Disordered Protein Micelles as Vehicles for Convection-Enhanced Drug Delivery to Glioblastoma Multiforme.

Lipid and micelle-based nanocarriers have been explored for anticancer drug delivery to improve accumulation and uptake in tumor tissue. As an experimental opportunity in this area, our lab has developed a protein-based micelle nanocarrier consisting of a hydrophilic intrinsically disordered protein (IDP) domain bound to a hydrophobic tail, termed IDP-2Yx2A. This construct can be used to encapsulate hydrophobic chemotherapeutics that would otherwise be too insoluble in water to be administered. In this study, we evaluate the in vivo efficacy of IDP-2Yx2A by delivering a highly potent but water-insoluble cancer drug, SN38, into glioblastoma multiforme (GBM) tumors via convection-enhanced delivery (CED). The protein carriers alone are shown to elicit minimal toxicity effects in mice; furthermore, they can encapsulate and deliver concentrations of SN38 that would otherwise be lethal without the carriers. CED administration of these drug-loaded micelles into mice bearing U251-MG GBM xenografts resulted in slowed tumor growth and significant increases in median survival times compared to nonencapsulated SN38 and PBS controls.

Innocence in the shadow of COVID-19: Plea decision making during a pandemic.

Over 95% of criminal convictions in the United States are the result of guilty pleas. Consequently, it is critical that we ensure the process of pleading guilty is as free of coercion as possible. Yet, research has indicated that incarcerating defendants to await trial could have an undue influence on their decision to plead guilty. The current research employed a novel computer simulation to examine the impact of the COVID-19 pandemic on plea decision making among the innocent and the guilty when faced with potential pretrial detention. While presenting COVID-related information to participants increased both true and false guilty pleas, further analyses indicated that concerns about COVID-19 weighed more heavily on the innocent than the guilty. These findings illustrate the negative impact a pandemic could have in combination with a system of pleas that often allows prosecutors to provide defendants with just one guaranteed respite from jail-a guilty plea. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Too much of a good thing: frequent retrieval can impair immediate new learning.

Interpolated testing can reduce mind-wandering and proactive interference, and improve note-taking. However, recent research using face-name-profession triads, has also shown that interpolated testing can impair new learning (Davis, Chan, & Wilford, 2017). In the current study, we further examined the impact of switching from testing to new learning, but with objectively-true materials. The study employed a 2 (Interpolated task: Test vs. Restudy) × 3 (Task-switch frequency: 0, 11, 35) between-participants design. In two experiments, participants restudied or retrieved originally-learned flag-country associations and learned new flag-capital (Experiment 1) or flag-export (Experiment 2) associations. Task-switch frequency varied such that participants switched to new learning trial(s) after every restudy/test trial (35-switches), after every three restudy/test trials (11-switches), or did not switch at all (0-switch). The results further demonstrate that retrieving previously-learned material can impair learning of new associations by replicating Davis et al. (2017) with objectively-true materials.

Mistaken eyewitness identification rates increase when either witnessing or testing conditions get worse.

We examined how giving eyewitnesses a weak recognition experience impacts their identification decisions. In 2 experiments we forced a weak recognition experience for lineups by impairing either encoding or retrieval conditions. In Experiment 1 (n = 245), undergraduate participants were randomly assigned to watch either a clear or a degraded culprit video and then viewed either a culprit-present or culprit-removed lineup identification procedure. In Experiment 2 (n = 227), all participants watched the same clear culprit video but were then randomly assigned to either view a clear or noise-degraded lineup procedure. Half of the participants viewed a culprit-present lineup procedure and the remaining participants viewed a culprit-removed lineup procedure. Not surprisingly, degrading either encoding or retrieval conditions led to a sharp drop in culprit identifications. Critically, and as predicted, degrading either encoding or retrieval conditions also led to a sharp increase in the identification of innocent persons. These results suggest that when a lineup procedure gives a witness a weak match-to-memory experience, the witness will lower her criterion for making an affirmative identification decision. This pattern of results is troubling because it suggests that witnesses who encounter lineups that do not include the culprit might have a tendency to use a lower criterion for identification than do witnesses who encounter lineups that actually include the culprit. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Caregiver socioemotional health as a determinant of child well-being in school-aged and adolescent Ugandan children with and without perinatal HIV exposure.

OBJECTIVE: Caregiver socio-emotional attributes are major determinants of child well-being. This investigation in vulnerable school-aged Ugandan children estimates relationships between children's well-being and their caregiver's anxiety, depression and social support. METHODS: Perinatally HIV-infected, HIV-exposed uninfected and HIV-unexposed Ugandan children and their caregivers were enrolled. Perinatal HIV status was determined by 18 months of age using DNA-polymerase chain-reaction test; status was confirmed via HIV rapid diagnostic test when children were 6-18 years old. Five indicators of child well-being (distress, hopelessness, positive future orientation, esteem and quality of life (QOL)) and caregivers' socioemotional status (depressive symptoms, anxiety and social support) were measured using validated, culturally adapted and translated instruments. Categories based on tertiles of each caregiver psychosocial indicator were defined. Linear regression analyses estimated percent differences (ß) and corresponding 95% confidence intervals (CI) for child well-being in relation to caregiver's psychosocial status. RESULTS: As per tertile increment, caregiver anxiety was associated with 2.7% higher distress (95%CI:0.2%, 5.3%) and lower self-esteem/QOL (ß = -1.3%/-2.6%; 95%CI: -5.0%,-0.2%) in their children. Child distress/hopelessness increased (ß = 3.3%/7.6%; 95%CI:0.4%, 14.7%) and self-esteem/QOL decreased 2.3% (ß = -2.3%/-4.4%; 95%CI: -7.2%, -1.3%) as per tertile increment in caregiver depression. Higher caregiver social support was associated with lower distress and higher positive outlook (ß = 3%; 95%CI:1.4%, 4.5%) in their children. HIV-infected/exposed children had most caregiver depression-related QOL deficit (ß = -5.2%/-6.8%; 95%CI: -12.4%, -0.2%) and HIV-unexposed children had most caregiver social support-related enhancements in positive outlook (ß=4.5%; 95%CI:1.9%, 7.1%). CONCLUSIONS: Caregiver anxiety, depressive symptoms and low social support were associated with worse well-being in school-aged and adolescent children. Improvement of caregiver mental health and strengthening caregiver social support systems may be a viable strategy for improving well-being of vulnerable children and adolescents in this setting.

OBJECTIF: Les attributs socio-affectifs des responsables d'enfants sont des déterminants majeurs du bien-être des enfants. Cette investigation menée auprès d'enfants ougandais vulnérables d'âge scolaire a estimé les relations entre le bien-être des enfants et l'anxiété, la dépression et le soutien social de leur responsable. MÉTHODES: Des enfants ougandais infectés par le VIH de manière périnatale, exposés au VIH mais non infectés, et non exposés au VIH ainsi que leurs responsables ont été inscrits. Le statut VIH périnatal a été déterminé à l'âge de 18 mois à l'aide du test de PCR de l'ADN; le statut a été confirmé par un test de diagnostic rapide du VIH chez les enfants âgés de 6 à 18 ans. Cinq indicateurs du bien-être de l'enfant (détresse, désespoir, orientation future positive, estime et qualité de vie (QV)), et le statut psychosocial des responsables (symptômes dépressifs, anxiété et soutien social) ont été mesurés à l'aide de méthodes validées, adaptées à la culture et respectées et d'outils traduits. Des catégories basées sur les tertiles de chaque indicateur psychosocial du responsable ont été définies. Des analyses de régression linéaire ont estimé les différences en pourcentage (ß) et les intervalles de confiance (IC) à 95% correspondants pour le bien-être de l'enfant par rapport au statut psychosocial de leurs responsables. RÉSULTATS: Par incrément de tertile, l'anxiété des responsables était associé à 2,7% de détresse plus élevé (IC95%: 0,2%, 5,3%) et de faible estime de soi/QV (ß = −1,3%/−2,6%; IC95%: −5,0%, −0,2%) chez leurs enfants. La détresse et le désespoir des enfants augmentaient (ß = 3,3%/7,6%; IC95%: 0,4%, 14,7%) et l'estime de soi/QV diminuait de 2,3% (ß = −2,3%/−4,4%; IC95%: −7,2%, −1,3%) par incrément de tertile de la dépression chez le responsable. Un soutien social plus élevé des responsables était associé à une détresse moindre et à une perspective positive plus élevée (ß = 3%; IC95%: 1,4%, 4,5%) chez leurs enfants. Les enfants infectés/exposés au VIH présentaient pour la plupart un déficit de QV lié à la dépression de leurs responsables (ß = −5,2%/−6,8%; IC95%: −12,4%, −0,2%), et ceux non exposés au VIH présentaient pour la plupart des améliorations en perspective positive liées au soutien social de leurs responsables (ß = 4,5%; IC95%: 1,9%, 7,1%). CONCLUSIONS: L'anxiété, les symptômes dépressifs et un faible soutien social du responsable étaient associés à un bien-être précaire chez les enfants d'âge scolaire et les adolescents. L'amélioration de la santé mentale des responsables et le renforcement des systèmes de soutien social pour les responsables peuvent constituer une stratégie viable pour améliorer le bien-être des enfants et des adolescents vulnérables dans cette région.

Telocytes (interstitial Cajal-like cells) in human Fallopian tubes.

BACKGROUND: Telocytes represent a relatively newly discovered population of cells found within the various tissues and organs, including Fallopian tubes. It is presumed that telocytes could serve as a sensor of hormone levels or regulate activity of muscle peristaltic movement. METHODS: Tissue sections from anatomically different parts of Fallopian tubes of 48 women (age 48.8±9.1) were stained for the expression of five different antigens: c-kit (CD117), CD34, vimentin, podoplanin (D2-40) and Dog-1. RESULTS: Telocytes form a network associated with the smooth muscle cells. From the mentioned antibodies, only anti-c-kit (CD117) seems to be relatively selective specific to the telocytes, others react also with numerous other cells and tissue structures. Our results when using antibodies against podoplanin and Dog-1 are in dissonance with recent literature - with regards to our results, they are not suitable for detection of telocytes. CONCLUSION: Methods of immunohistochemistry are suitable for identification of telocytes in Fallopian tubes. C-kit (CD117) antigens are useful for routine identification of telocytes in histological sections. This antigen can be combined with CD34 or vimentin in cases of double staining immunohistochemistry.

Ultrastructural changes of kidney in diabetic rats.

OBJECTIVES: To demonstrate histopathological changes in diabetic kidneys of the rat on ultrastructural level with focusing on glomerular cellular environment. METHODS: Male Wistar rats were administered streptozotocin and after 8 weeks, their kidneys were studied using qualitative transmission electron microscope analysis. RESULTS: In diabetic kidneys, the presence of irregularly thickened glomerular membrana basalis (GBM), often up to six times as compared to healthy kidney GBM, mainly around peripheral capillary loops, was striking. We also demonstrated lamination and split appearance of GBM, with presence of delicate fibrillar structure, which was absent within normal GBM. Accumulation of mesangial matrix was found only occasionally. CONCLUSION: Model may be useful to better understand the mechanisms that play role in the progression of DM-induced renal disease and to comprehend the morphological changes, which this process leaves within the tissue. The clear association between ultra-structure and functional markers may not be necessary (Fig. 4, Ref. 27).

Ultrastructural analysis of different human mesenchymal stem cells after in vitro expansion: a technical review.

Transmission electron microscopy reveals ultrastructural details of cells, and it is a valuable method for studying cell organelles. That is why we used this method for detailed morphological description of different adult tissuederived stem cells, focusing on the morphological signs of their functions (proteosynthetic activity, exchange with external environment, etc.) and their comparison. Preparing a specimen from the cell culture suitable for transmission electron microscopy is, however, much more challenging than routine tissue processing for normal histological examination. There are several issues that need to be solved while working with cell pellets instead of solid tissue. Here we describe a simple protocol for the isolation and culture of mesenchymal stem cells from different adult tissues, with applications to stem cell biology and regenerative medicine. Since we are working with population of cells that was obtained after many days of passaging, very efficient and gentle procedures are highly necessary. We demonstrated that our semi-conservative approach regarding to histological techniques and processing of cells for transmission electron microscopy is a well reproducible procedure which results in quality pictures and images of cell populations with minimum distortions and artifacts. We also commented about riskiest steps and histochemical issues (e.g., precise pH, temperature) while preparing the specimen. We bring full and detailed procedures of fixation, post-fixation, infiltration, embedding, polymerization and contrasting of cell obtained from in vitro cell and tissue cultures, with modifications according to our experience. All this steps are essential for us to know more about adult stem cells derived from different sources or about other random cell populations. The knowledge about detailed ultra-structure of adult stem cells cultured in vitro are also essential for their using in regenerative medicine and tissue engineering.

[New views on the functional morphology of human clitoris]. / Nové pohlady na funkcnú morfológiu klitorisu.

The clitoris is the female external sexual organ and is composed of erectile bodies. The distal portion of the vagina, clitoris and urethra form an integrated entity sui generis. All these components share a common vasculature and nerve supply and during sexual stimulation they respond as one functional unit. The clitoris is closely linked to the mechanism of sexual arousal in women. Glans has a dense network of receptors, innervated often with a several nerves at the same time - taking care of tactile sensitivity, thus, standing on the beginning of the journey, which culminates in orgasm. Nervus dorsalis clitoridis, which is a branch of n. pudendus, takes care of sensitive innervation. For blood supply is responsible a. clitoridis, which is a branch of a. pudenda interna. The most common congenital developmental anomalies of the clitoris include: clitoromegaly, penis-like clitoris and bifid clitoris. All, however, are among the relatively rare birth defects. Mechanism of orgasm gets attention between both laic and scientific community, although to this date there are speculations about its exact mechanism. There is relevant opinion, influenced by Freuds doctrine, which strictly recognizes two kinds of female orgasms - vaginal and clitoral, and, according to proponents of this theory, only the second mentioned is caused by stimulation of the clitoris. The second school unifies the term orgasm and claims that only clitoral stimulation (digital, penile, cunnilingus) and contraction of striated perineal muscle are responsible for orgasm, whether the glans (external part) or the body of the clitoris from the vaginal approach is stimulated. Therewithal, special term for mythical and still undocumented (despite many attempts and bold claims about its finding) G spot (named after Ernst Gräfenberg, a German doctor who predicted the existence of this place) is redundant. Important role in the regulation of female sexuality and responsiveness play a hormonal influences and varying concentrations of neurotransmitters.

Retrieval enhances eyewitness suggestibility to misinformation in free and cued recall.

Immediately recalling a witnessed event can increase people's susceptibility to later postevent misinformation. But this retrieval-enhanced suggestibility (RES) effect has been shown only when the initial recall test included specific questions that reappeared on the final test. Moreover, it is unclear whether this phenomenon is affected by the centrality of event details. These limitations make it difficult to generalize RES to criminal investigations, which often begin with free recall prior to more specific queries from legal officials and attorneys. In 3 experiments, we examined the influence of test formats (free recall vs. cued recall) and centrality of event details (central vs. peripheral) on RES. In Experiment 1, both the initial and final tests were cued recall. In Experiment 2, the initial test was free recall and the final test was cued recall. In Experiment 3, both the initial and final tests were free recall. Initial testing increased misinformation reporting on the final test for peripheral details in all experiments, but the effect was significant for central details only after aggregating the data from all 3 experiments. These results show that initial free recall can produce RES, and more broadly, that free recall can potentiate subsequent learning of complex prose materials.

Appearances can be deceiving: instructor fluency increases perceptions of learning without increasing actual learning.

The present study explored the effects of lecture fluency on students' metacognitive awareness and regulation. Participants watched one of two short videos of an instructor explaining a scientific concept. In the fluent video, the instructor stood upright, maintained eye contact, and spoke fluidly without notes. In the disfluent video, the instructor slumped, looked away, and spoke haltingly with notes. After watching the video, participants in Experiment 1 were asked to predict how much of the content they would later be able to recall, and participants in Experiment 2 were given a text-based script of the video to study. Perceived learning was significantly higher for the fluent instructor than for the disfluent instructor (Experiment 1), although study time was not significantly affected by lecture fluency (Experiment 2). In both experiments, the fluent instructor was rated significantly higher than the disfluent instructor on traditional instructor evaluation questions, such as preparedness and effectiveness. However, in both experiments, lecture fluency did not significantly affect the amount of information learned. Thus, students' perceptions of their own learning and an instructor's effectiveness appear to be based on lecture fluency and not on actual learning.

[The structural basis for transport through the Fallopian tube]. / Struktúrny základ transportnej funkcie vajíckovodu.

The Fallopian tube has until recently been a neglected structure, bypassed by in vitro fertilization and seen only as a tube that transports the oocyte or early embryo to the uterus. More recently, its role is even more undervalued after the introduction of techniques of assisted reproduction, in which the Fallopian tubes become like unnecessary. The Fallopian tube performs several important functions. It captures the oocyte after ovulation, maintains and controls the migration of spermatozoa to the site of fertilization. It provides the special microenvironment for fertilization; nourishes the early embryo while it is being carried to the uterus and amplifies signals from embryo to the mother. In our article we conducted a systematic review of relevant articles found in PubMed, Scopus and ISI Web of Knowledge, focused on the new insights into the functional morphology of Fallopian tube. We described the possible function of muscle layer motility, ciliary activity and tubal fluid movement on transport of gamets / embryo, as well as we mentioned the negative factors (such as smoking, chlamydial infection or endometriosis) affecting the transport through the Fallopian tube.

Does facial processing prioritize change detection?: change blindness illustrates costs and benefits of holistic processing.

There is broad consensus among researchers both that faces are processed more holistically than other objects and that this type of processing is beneficial. We predicted that holistic processing of faces also involves a cost, namely, a diminished ability to localize change. This study (N = 150) utilized a modified change-blindness paradigm in which some trials involved a change in one feature of an image (nose, chin, mouth, hair, or eyes for faces; chimney, porch, window, roof, or door for houses), whereas other trials involved no change. People were better able to detect the occurrence of a change for faces than for houses, but were better able to localize which feature had changed for houses than for faces. Half the trials used inverted images, a manipulation that disrupts holistic processing. With inverted images, the critical interaction between image type (faces vs. houses) and task (change detection vs. change localization) disappeared. The results suggest that holistic processing reduces change-localization abilities.

Cytotoxicity and mode of action of the potential cytostatic drug oracin.

Primary screening in vitro and study on the mode of action of oracin in Ehrlich ascites carcinoma cells have been performed. The measure of the cytotoxic effect was the degree of inhibition of 14C-adenine and 14C-valine incorporation into TCA insoluble fraction of Ehrlich ascites carcinoma (EAC) cells. The inhibitory effect was characterized by IC50 values. The biosynthesis of nucleic acides indicated by the incorporation of 14C-adenine was more sensitive (IC50 = 66 micromol/ l) than the biosynthesis of proteins indicated by the incorporation of 14C-valine (IC50 = 196 micromol/l). To elucidate the biochemical mode of action, the effect of oracin on dynamics of biosynthesis of macromolecules indicated by the incorporation rate of [14C] labeled precursors (adenine, thymidine, uridine, valine) into appropriate macromolecules of EAC cells was studied. Oracin inhibited incorporation of all four precursors into the trichloracetic acid - insoluble fraction of Ehrlich ascites cells. The extent of inhibition was dependent on both time and drug concentration. We found that oracin inhibited activity of topoisomerase II by 100% at concentration 5 to 15 micromol/l.

The distribution of aminoacylase I among mammalian species and localization of the enzyme in porcine kidney.

Aminoacylase I (Acy-1, EC 3.5.1.14) is found in many mammalian tissues, with highest activities occurring in kidney. The enzyme hydrolyzes a variety of N-acylated amino acids; however, the physiological role and the exact cellular localization of Acy-1 are still a matter of debate. The comparison of Acy-1 activities in kidney and liver homogenates of 11 mammalian species showed that the enzyme is most abundant in true herbivores such as sheep and cattle as well as in omnivores, while activities were very low in both rodents and the cat. Acy-1 activity was not detected in livers of dogs of five different breeds. Using in situ hybridization of porcine kidney sections with DIG-labeled RNA probes, Acy-1 mRNA was shown to be evenly distributed throughout the tubular system, while glomeruli and the interstitium were free of stain. During subcellular fractionation, porcine Acy-1 behaved like a typical cytosolic enzyme. Commonly, Acy-1 is thought to catalyze hydrolytic reactions, i.e., the formation of free amino acids from acylated derivatives. Based on the present results and literature data, we propose a novel hypothesis, i.e., that Acy-1 catalyzes the synthesis (rather than the hydrolysis) of hippurate that is formed as a detoxification product of aromatic compounds.

Cytoxicity of 1-alkylperhydroazepine N-oxides and quantitative structure-activity relationships.

A new class of nonaromatic amine oxides was tested for cytotoxic activity. The main aim of the present investigation was to screen a series of 1-alkylperhydroazepine N-oxides for in vitro cytotoxicity and to find out whether there is a quantitative structure-activity correlation (QSAR) between cytotoxic effect and structure (as a structural parameter the number of carbon atoms m in the alkyl chain was used). Cytotoxicity was determined here by inhibition of incorporation of [14C]adenine into nucleic acid or [14C]valine into proteins in Ehrlich ascites carcinoma (EAC) cells. On the basis of primary screening, one of the most active compounds, namely 1-tetradecylperhydroazepine N-oxide (TPNO), was chosen for further biochemical study. The drug inhibited the incorporation rate of [14C] labeled precursors (adenine, thymidine, uridine, valine) into appropriate macromolecules of Ehrlich cells. The extent of inhibition was dependent on both time and drug concentration. The lengthening of the alkyl chain in 1-alkylperhydroazepine N-oxides positively affected their cytotoxic activity in EAC cells. For these compounds the optimal m value is 12-14.

Effects of 1-tetradecylperhydroazepine and 1-pentadecylpiperidine N-oxides on Ehrlich ascites mitochondria.

Non-aromatic amine oxides are widely known and used compounds. A great number of amine oxides occurring in nature, or prepared synthetically, are biologically active compounds (antimetabolites and chemotherapics, cancerostatic compounds, etc.). From seven series of newly synthesized amine oxides (63 compounds), 1-alkylperhydroazepine N-oxides (PHNO) and 1-alkylpiperadine N-oxides (PINO) have been chosen for further investigation. The effects of 8 derivatives of PHNO and 8 derivatives of PINO on state 3 and 4 respiration of Ehrlich ascites mitochondria (EAM) have been studied. Derivatives with longer side-chain significantly affected respiration of EAM according to the substrates used. To elucidate the mode of action, the most potent amine oxides from each series, 1-tetradecylperhydroazepine N-oxide (tPHNO) and 1-pentadecylpiperidine N-oxide (pPINO) have been chosen for further study. Both amine oxides stimulated state 4 respiration with glutamate-malate and succinate as substrates. The effect on state 3 respiration depended on the substrates used. Both tPHNO and pPINO were able to release respiration of EAM previously inhibited by oligomycin, both decreased the level of ATP in EAM. ATPase activity was significantly stimulated by both drugs only in higher concentrations. A possible mode of action of amine oxides on oxidative phosphorylation and the relationship between chemical structure are discussed.

Effects of 4-alkylmorpholine N-oxides on ATP-producing processes in Ehrlich ascites and L1210 leukaemia cells.

The main purpose of the present investigation was to study the effect of the homologous series of 4-alkylmorpholine N-oxides on ATP-producing processes in Ehrlich ascites and L1210 murine leukaemia cells. The effects on aerobic glucose consumption, lactic acid formation, content of total (T-SH) and non-protein thiol groups (NP-SH), endogenous and exogenous respiration and the level of ATP in tumour cells incubated in vitro were investigated. 4-Dodecylmorpholine N-oxide (DMNO), one of the most active compounds, decreased the level of ATP immediately after addition to the suspension of Ehrlich cells in an ice bath. After 2 h incubation at 37 degrees C the drop in the ATP level was much lower. A possible explanation for the decrease in the ATP level might be interaction of the amine oxide with the cell membrane.

Effect of N-tricyanovinylamines on the level of glutathione in hepatocytes.

The effects of N-substituted tricyanovinylamines (N-TCVA; RNHC(CN)=C(CN)2) have been studied on rat hepatocytes and liver mitochondria. Derivatives of N-TCVA act on oxidative phosphorylation as uncouplers, and react with thiols within pH 5.0-8.5. N-Isobutyl-, N-benzyl-, and N-cyclohexyl-TCVA influence the level of GSH and GSSG in isolated hepatocytes. They can act as oxidants, but the level of GSSG increases (about 40%) only if the concentration of N-TCVA is higher than 1 micromol/l. If N-TCVA is added to a final concentration higher than 50 micromol/l a decrease of GSH and GSSG level is observed. Derivatives of N-TCVA also influence the level of GSH and GSSG in mitochondria. At 40-400 micromol/l N-TCVA in the incubation medium the level of GSSG increased and the ratio GSH/GSSG was influenced, but the level of total SH groups did not decrease.

Effect of membrane active 1-alkylpiperidine N-oxides on glycolysis, respiration and ATP level in tumor cells.

The aim of this study was to study the effect of the homologous series of 1-alkylpyrrolidine N-oxides on ATP-producing processes in Ehrlich ascites and L1210 murine leukemia cells. 1-Decylpiperidine N-oxide (deP-NO), one of the active compounds, significantly stimulated the course of aerobic glycolysis of Ehrlich cells. Derivatives with longer side-chains markedly inhibited endogenous respiration of both tumor cells. dePNO, immediately after addition to the suspension of Ehrlich cells in an ice bath, markedly decreased the level of ATP in Ehrlich ascites cells. The decrease in ATP level might be explained through impairment of cell membrane integrity.