Evaluation of the Acute Oral Toxicity Class of Trinuclear Chromium(III) Glycinate Complex in Rat

Chromium(III) is considered as an essential element playing a role in carbohydrate and lipid metabolism, and various chemical forms of this element are widely used in dietary supplements. A new trinuclear chromium(III) glycinate complex [Cr3O(NH2CH2CO2)6(H2O)3]+NO3− (CrGly), an analogue of Cr3 (trinuclear Cr(III) propionate complex) has been synthesized as a potential source of supplementary Cr. In this study, we evaluated the acute toxicity class of CrGly in Wistar rats applying the OECD 423 procedure. Male and female Wistar rats (n = 12, 6 ♀ and 6 ♂) were given by gavage either a single dose of CrGly 2,000 mg/kg body mass (equals to 300 mg Cr(III)/kg body mass; in aqueous solution) or equivalent volumes of distilled water and fed ad libitum commercial Labofeed B diet, and observed carefully for 14 days, then sacrificed to collect blood and internal organs for biochemical and histologic examination. No death cases were detected. No abnormalities in animal behavior, body mass gains, gross organ histology, or blood morphology and biochemistry were observed. The results demonstrate that LD50 of CrGly is greater than 2,000 mg/kg when administrated orally to rat; thus, this compound appears to belong to the fifth category in the GHS system or the fourth class (“unclassified”) in the EU classification system

The Neuronal Transition Probability (NTP) Model for the Dynamic Progression of Non-REM Sleep EEG: The Role of the Suprachiasmatic Nucleus

Little attention has gone into linking to its neuronal substrates the dynamic structure of non-rapid-eye-movement (NREM) sleep, defined as the pattern of time-course power in all frequency bands across an entire episode. Using the spectral power time-courses in the sleep electroencephalogram (EEG), we showed in the typical first episode, several moves towards-and-away from deep sleep, each having an identical pattern linking the major frequency bands beta, sigma and delta. The neuronal transition probability model (NTP) – in fitting the data well – successfully explained the pattern as resulting from stochastic transitions of the firing-rates of the thalamically-projecting brainstem-activating neurons, alternating between two steady dynamic-states (towards-and-away from deep sleep) each initiated by a so-far unidentified flip-flop. The aims here are to identify this flip-flop and to demonstrate that the model fits well all NREM episodes, not just the first. Using published data on suprachiasmatic nucleus (SCN) activity we show that the SCN has the information required to provide a threshold-triggered flip-flop for timing the towards-and-away alternations, information provided by sleep-relevant feedback to the SCN. NTP then determines the pattern of spectral power within each dynamic-state. NTP was fitted to individual NREM episodes 1–4, using data from 30 healthy subjects aged 20–30 years, and the quality of fit for each NREM measured. We show that the model fits well all NREM episodes and the best-fit probability-set is found to be effectively the same in fitting all subject data. The significant model-data agreement, the constant probability parameter and the proposed role of the SCN add considerable strength to the model. With it we link for the first time findings at cellular level and detailed time-course data at EEG level, to give a coherent picture of NREM dynamics over the entire night and over hierarchic brain levels all the way from the SCN to the EEG

Highly symmetric POVMs and their informational power

We discuss the dependence of the Shannon entropy of normalized finite rank-1 POVMs on the choice of the input state, looking for the states that minimize this quantity. To distinguish the class of measurements where the problem can be solved analytically, we introduce the notion of highly symmetric POVMs and classify them in dimension two (for qubits). In this case we prove that the entropy is minimal, and hence the relative entropy (informational power) is maximal, if and only if the input state is orthogonal to one of the states constituting a POVM. The method used in the proof, employing the Michel theory of critical points for group action, the Hermite interpolation and the structure of invariant polynomials for unitary-antiunitary groups, can also be applied in higher dimensions and for other entropy-like functions. The links between entropy minimization and entropic uncertainty relations, the Wehrl entropy and the quantum dynamical entropy are described.Comment: 40 pages, 3 figure

Neural Substrate of Cold-Seeking Behavior in Endotoxin Shock

Systemic inflammation is a leading cause of hospital death. Mild systemic inflammation is accompanied by warmth-seeking behavior (and fever), whereas severe inflammation is associated with cold-seeking behavior (and hypothermia). Both behaviors are adaptive. Which brain structures mediate which behavior is unknown. The involvement of hypothalamic structures, namely, the preoptic area (POA), paraventricular nucleus (PVH), or dorsomedial nucleus (DMH), in thermoregulatory behaviors associated with endotoxin (lipopolysaccharide [LPS])-induced systemic inflammation was studied in rats. The rats were allowed to select their thermal environment by freely moving in a thermogradient apparatus. A low intravenous dose of Escherichia coli LPS (10 µg/kg) caused warmth-seeking behavior, whereas a high, shock-inducing dose (5,000 µg/kg) caused cold-seeking behavior. Bilateral electrocoagulation of the PVH or DMH, but not of the POA, prevented this cold-seeking response. Lesioning the DMH with ibotenic acid, an excitotoxin that destroys neuronal bodies but spares fibers of passage, also prevented LPS-induced cold-seeking behavior; lesioning the PVH with ibotenate did not affect it. Lesion of no structure affected cold-seeking behavior induced by heat exposure or by pharmacological stimulation of the transient receptor potential (TRP) vanilloid-1 channel (“warmth receptor”). Nor did any lesion affect warmth-seeking behavior induced by a low dose of LPS, cold exposure, or pharmacological stimulation of the TRP melastatin-8 (“cold receptor”). We conclude that LPS-induced cold-seeking response is mediated by neuronal bodies located in the DMH and neural fibers passing through the PVH. These are the first two landmarks on the map of the circuitry of cold-seeking behavior associated with endotoxin shock

Circuit-based interrogation of sleep control.

Sleep is a fundamental biological process observed widely in the animal kingdom, but the neural circuits generating sleep remain poorly understood. Understanding the brain mechanisms controlling sleep requires the identification of key neurons in the control circuits and mapping of their synaptic connections. Technical innovations over the past decade have greatly facilitated dissection of the sleep circuits. This has set the stage for understanding how a variety of environmental and physiological factors influence sleep. The ability to initiate and terminate sleep on command will also help us to elucidate its functions within and beyond the brain

Ostriches Sleep like Platypuses

Mammals and birds engage in two distinct states of sleep, slow wave sleep (SWS) and rapid eye movement (REM) sleep. SWS is characterized by slow, high amplitude brain waves, while REM sleep is characterized by fast, low amplitude waves, known as activation, occurring with rapid eye movements and reduced muscle tone. However, monotremes (platypuses and echidnas), the most basal (or ‘ancient’) group of living mammals, show only a single sleep state that combines elements of SWS and REM sleep, suggesting that these states became temporally segregated in the common ancestor to marsupial and eutherian mammals. Whether sleep in basal birds resembles that of monotremes or other mammals and birds is unknown. Here, we provide the first description of brain activity during sleep in ostriches (Struthio camelus), a member of the most basal group of living birds. We found that the brain activity of sleeping ostriches is unique. Episodes of REM sleep were delineated by rapid eye movements, reduced muscle tone, and head movements, similar to those observed in other birds and mammals engaged in REM sleep; however, during REM sleep in ostriches, forebrain activity would flip between REM sleep-like activation and SWS-like slow waves, the latter reminiscent of sleep in the platypus. Moreover, the amount of REM sleep in ostriches is greater than in any other bird, just as in platypuses, which have more REM sleep than other mammals. These findings reveal a recurring sequence of steps in the evolution of sleep in which SWS and REM sleep arose from a single heterogeneous state that became temporally segregated into two distinct states. This common trajectory suggests that forebrain activation during REM sleep is an evolutionarily new feature, presumably involved in performing new sleep functions not found in more basal animals

Hepatic alterations are accompanied by changes to bile acid transporter-expressing neurons in the hypothalamus after traumatic brain injury

Annually, there are over 2 million incidents of traumatic brain injury (TBI) and treatment options are non-existent. While many TBI studies have focused on the brain, peripheral contributions involving the digestive and immune systems are emerging as factors involved in the various symptomology associated with TBI. We hypothesized that TBI would alter hepatic function, including bile acid system machinery in the liver and brain. The results show activation of the hepatic acute phase response by 2 hours after TBI, hepatic inflammation by 6 hours after TBI and a decrease in hepatic transcription factors, Gli 1, Gli 2, Gli 3 at 2 and 24 hrs after TBI. Bile acid receptors and transporters were decreased as early as 2 hrs after TBI until at least 24 hrs after TBI. Quantification of bile acid transporter, ASBT-expressing neurons in the hypothalamus, revealed a significant decrease following TBI. These results are the first to show such changes following a TBI, and are compatible with previous studies of the bile acid system in stroke models. The data support the emerging idea of a systemic influence to neurological disorders and point to the need for future studies to better define specific mechanisms of action

Interactions between components of dietary supplements: a case of quercetin and vitamin C

W pracy przedstawiono wyniki badań nad wpływem pH środowiska na aktywność przeciwrodnikową kwercetyny w obecności witaminy C (kwasu askorbinowego). Stwierdzono, że aktywność przeciwrodnikowa kwercetyny, zmierzona w teście TEAC (Trolox Equivalent Antioxidant Capacity), ulega znacznemu obniżeniu w pH 4,5-9,0 w wyniku interakcji z kwasem askorbinowym. Wykonano odpowiednie obliczenia kwantowo-chemiczne w celu wyjaśnienia obserwowanego antagonistycznego oddziaływania pomiędzy tymi przeciwutleniaczami.In the present study, the effect of pH of the surrounding medium on the radical-scavenging activity of quercetin in the presence of vitamin C (ascorbic acid) was investigated. It was found that at pH 4.5-9.0 radical-scavenging activity of quercetin in the TEAC (Trolox Equivalent Antioxidant Capacity) assay is strongly reduced by ascorbic acid as a result of their interactions. Some relevant quantum-chemical calculations were performed to get some insight into the mechanism of observed antagonistic interaction between these two popular antioxidants

Synthesis, thermal stability, and antioxidant activity of long-chain alkyl esters of ferulic acid

Tłuszcze naturalne bogate w jedno- i wielonienasycone kwasy tłuszczowe są podstawowymi składniami żywności, które w istotny sposób wpływają na prawidłowe funkcjonowanie organizmu człowieka. Niestety tłuszcze te charakteryzują się niską stabilnością, głównie ze względu na dużą podatność na procesy utleniania. Stosuje się wiele zabiegów w celu wyeliminowania tych niekorzystnych przemian. Wykorzystywane obecnie przeciwutleniacze komercyjne, pomimo licznych zalet, mogą wzbudzać kontrowersje związane z niepożądaną aktywnością biologiczną lub niską stabilnością w warunkach przetwarzania żywności. Z tego powodu dąży się do poszukiwania nowych przeciwutleniaczy, które mogłyby stanowić alternatywę dla obecnie stosowanych przeciwutleniaczy. Celem niniejszej pracy było opracowanie metody otrzymywania wybranych, długołańcuchowych estrów kwasu ferulowego. Dokonano identyfikacji otrzymanych przeciwutleniaczy na podstawie wyników badań spektroskopowych i analizy elementarnej. Przeprowadzono analizę termiczną estrów, która obejmowała analizę termograwimetryczną (TG) oraz skaningową kalorymetrię różnicową. Uzyskane wyniki porównano z wynikami uzyskanymi dla wolnego kwasu ferulowego oraz danymi literaturowymi dotyczącymi popularnych przeciwutleniaczy komercyjnych. W pracy dokonano również wstępnego porównania właściwości przeciwutleniających ferulanu tetradcylu i BHT.Natural lipids, rich in mono- and polyunsaturated fatty acids, are basic components of food; they significantly impact the accurate functioning of human organism. Unfortunately, those lipids are characterized by instability owing to their high susceptibility to oxidation processes. Many treatment procedures are applied to eliminate those adverse changes. In spite of their many advantages, the currently used commercial antioxidants may arouse controversy attributed to the undesirable biological activity or low stability under the food processing conditions. Therefore, there are attempts at searching for new antioxidants that might be an alternative to the presently used antioxidants. The objective of the research study was to develop a method to synthesize long-chain alkyl esters of ferulic acid. The antioxidants produced were identified based on the results of spectroscopic investigations and elemental analysis. A thermal analysis of esters was performed, which comprised thermogravimetry (TG) and differential scanning calorimetry (DSC). The results obtained were compared with the results obtained for the free ferulic acid and with data in the reference literature on commercial antioxidants. In the research study, the antioxidant activity of tetradecyl ferulate and of BHT were pre-compared