Cyclic Voltammetry and Computational Chemistry Studies on the Evaluation of the Redox Behavior of Parabens and other Analogues

Parabens are antimicrobial preservatives widely used in pharmaceutical, cosmetic and food industries. The alkyl chain connected to the ester group defines some important physicochemical characteristics of these compounds, including the partition coefficient and redox properties. The voltammetric and computational analyses were carried out in order to evaluate the redox behavior of these compounds and other phenolic analogues. A strong correlation between chemical substituents inductive effects of parabens with redox potentials was observed. Using cyclic voltammetry and glassy carbon working electrode, only one irreversible anodic peak was observed around 0.8 V for methylparaben (MP), ethylparaben (EP), propylparaben (PP), butylparaben (BP), benzylparaben (BzP) and p-substituted phenolic analogues. The electrodonating inductive effect of alkyl groups was demonstrated by the anodic oxidation potential shift to lower values as the carbon number increases and, therefore the parabens (and other phenolic analogues) oxidation processes to the quinonoidic forms showed great dependence on the substituent pattern.

Molting dynamics and juvenile hormone titer profiles in the nymphal stages of a lower termite, Cryptotermes secundus (Kalotermitidae) - signatures of developmental plasticity

Termites are social cockroaches and this sociality is founded on a high plasticity during development. Three molting types (progressive, stationary and regressive molts) are fundamental to achieve plasticity during alate/sexual development, and they make termites a major challenge to any model on endocrine regulation in insect development. As the endocrine signatures underpinning this plasticity are barely understood, we studied the developmental dynamics and their underlying juvenile hormone OH) titers in a wood-dwelling termite. Cryptotermes secundus, which is characterized by an ancestral life style of living in dead wood and individuals being totipotent in development. The following general pattern elements could be identified during winged sexual development (i) regressive molts were accompanied by longer intermolt periods than other molting types, (ii) JH titers decreased gradually during the developmental transition from larva (immatures without wing buds), to nymph (immatures with wing buds), to winged adult, (iii) in all nymphal stages, the JH titer rose before the next molt and dropped thereafter within the first week, (iv) considerable variation in JH titers occurred in the midphase of the molting cycle of the 2nd and 3rd nymphal instar, inferring that this variation may reflect the underlying endocrine signature of each of the three molting types, (v) the 4th nymphal instar, the shortest of all, seems to be a switch point in development, as nymphs in this stage mainly developed progressively. When comparing these patterns with endocrine signatures seen in cockroaches, the developmental program of Cryprotermes can be interpreted as a co-option and repetitive use of hormonal dynamics of the post dorsal-closure phase of cockroach embryonic development. (C) 2012 Elsevier Ltd. All tights reserved.

Cyclic voltammetry and computational chemistry studies on the evaluation of the redox behavior of parabens and other analogues

Parabens are antimicrobial preservatives widely used in pharmaceutical, cosmetic and food industries. The alkyl chain connected to the ester group defines some important physicochemical characteristics of these compounds, including the partition coefficient and redox properties. The voltammetric and computational analyses were carried out in order to evaluate the redox behavior of these compounds and other phenolic analogues. A strong correlation between chemical substituents inductive effects of parabens with redox potentials was observed. Using cyclic voltammetry and glassy carbon working electrode, only one irreversible anodic peak was observed around 0.8 V for methylparaben (MP), ethylparaben (EP), propylparaben (PP), butylparaben (BP), benzylparaben (BzP) and p-substituted phenolic analogues. The electrodonating inductive effect of alkyl groups was demonstrated by the anodic oxidation potential shift to lower values as the carbon number increases and, therefore the parabens (and other phenolic analogues) oxidation processes to the quinonoidic forms showed great dependence on the substituent pattern.

Caffeine determination at a carbon fiber ultramicroelectrodes by fast-scan cyclic voltammetry

Caffeine determination using a fast-scan voltammetric procedure at a carbon fiber ultramicroelectrode (CF-UME) is described. The CF-UME was submitted to electrochemical pretreatment. Parameters such as number of acquisition cycles, scan rate, potential window, and the electrochemical surface pretreatment were optimized. Using the optimized conditions, it was possible to achieve a LDR from 10.0 up to 200 μmol L-1, with a LOD of 3.33 μmol L-1. The method has been applied in the determination of caffeine in commercial samples, with errors of 1.0-3.5% in relation to the label values and recoveries of 97-114% within the linear range.

Synthesis of unstable cyclic peroxides for chemiluminescence studies

Cyclic four-membered ring peroxides are important high-energy intermediates in a variety of chemi and bioluminescence transformations. Specifically, α-peroxylactones (1,2-dioxetanones) have been considered as model systems for efficient firefly bioluminescence. However, the preparation of such highly unstable compounds is extremely difficult and, therefore, only few research groups have been able to study the properties of these substances. In this study, the synthesis, purification and characterization of three 1,2-dioxetanones are reported and a detailed procedure for the known synthesis of diphenoyl peroxide, another important model compound for the chemical generation of electronically excited states, is provided. For most of these peroxides, the complete spectroscopic characterization is reported here for the first time.

Prostaglandin treatment at the onset of norgestomet and estradiol-based synchronization protocols did not alter the ovarian follicular dynamics or pregnancy per timed artificial insemination in cyclic Bos indicus heifers

The aim of the present study was to evaluate the effects of the PGF2˛treatment givenat the onset of a synchronization of ovulation protocol using a norgestomet (NORG) earimplant on ovarian follicular dynamics (Experiment 1) and pregnancy per AI (P/AI; Exper-iment 2) in cyclic (CL present) Bos indicus heifers. In Experiment 1, a total of 46 heiferswere presynchronized using two consecutive doses of PGF2˛12 days apart. At first dayof the synchronization protocol the heifers received implants containing 3 mg of NORGand 2 mg of estradiol benzoate (EB). At the same time, heifers were randomly assignedto receive 150 mg of d-cloprostenol (n = 23; PGF2˛) or no additional treatment (n = 23;Control). When the ear implants were removed 8 days later, all heifers received a PGF2˛treatment and 1 mg of EB was given 24 h later. The follicular diameter and interval toovulation were determined by transrectal ultrasonography. No effects of PGF2˛treat-ment on the diameter of the largest follicle present were observed at implant removal(PGF2˛= 9.8 ± 0.4 vs. Control = 10.0 ± 0.3 mm; P = 0.73) or after 24 h (PGF2˛= 11.1 ± 0.4 vs.Control = 11.0 ± 0.4 mm; P = 0.83). No differences in the time of ovulation after ear implantremoval (PGF2˛= 70.8 ± 1.2 vs. Control = 73.3 ± 0.9 h; P = 0.10) or in the ovulation rate(PGF2˛= 87.0 vs. Control = 82.6%; P = 0.64) between treatments were observed. In Experi-ment 2, 280 cyclic heifers were synchronized using the same experimental design describedabove (PGF2˛; n = 143 and Control; n = 137), at random day of the estrous cycle. All heifersreceived 300 IU of equine chorionic gonadotropin (eCG) and 0.5 mg of estradiol cypionate(as ovulatory stimulus) when the NORG ear implants were removed. Timed artificial insem-ination (TAI) was performed 48 h after implant removal and the pregnancy diagnosis wasconducted 30 days later. No effects on the P/AI due to PGF2˛treatment were observed(PGF2˛= 51.7 vs. Control = 57.7%; P = 0.29). In conclusion, PGF2˛treatment at the onset ofNORG-based protocols for the synchronization of ovulation did not alter the ovarian follic-ular responses or the P/AI in cyclic Bos indicus beef heifers synchronized for TAI.

Fatigue crack growth assessments in welded components including crack closure effects: Experiments and 3-D numerical modeling

This work provides a numerical and experimental investigation of fatigue crack growth behavior in steel weldments including crack closure effects and their coupled interaction with weld strength mismatch. A central objective of this study is to extend previously developed frameworks for evaluation of crack clo- sure effects on FCGR to steel weldments while, at the same time, gaining additional understanding of commonly adopted criteria for crack closure loads and their influence on fatigue life of structural welds. Very detailed non-linear finite element analyses using 3-D models of compact tension C ( T ) fracture spec- imens with center cracked, square groove welds provide the evolution of crack growth with cyclic stress intensity factor which is required for the estimation of the closure loads. Fatigue crack growth tests con- ducted on plane-sided, shallow-cracked C ( T ) specimens provide the necessary data against which crack closure effects on fatigue crack growth behavior can be assessed. Overall, the present investigation pro- vides additional support for estimation procedures of plasticity-induced crack closure loads in fatigue analyses of structural steels and their weldments

Dynamics of follicular growth and progesterone concentrations in cyclic and anestrous suckling Nelore cows (Bos indicus) treated with progesterone, equine chorionic gonadotropin, or temporary calf removal

The objective of this study was to investigate the effects of eCG and temporary calf removal (TCR) associated with progesterone (P4) treatment on the dynamics of follicular growth, CL size, and P4 concentrations in cyclic (n ¼ 36) and anestrous (n ¼ 30) Nelore cows. Cyclic (C) and anestrous (A) cows were divided into three groups. The control group received 2 mg of estradiol benzoate via intramuscular (IM) injection and an intravaginal device containing 1.9 g of P4 on Day 0. On Day 8, the device was removed, and the animals received 12.5 mg of dinoprost tromethamine IM. After 24 hours, the animals received 1 mg of estradiol benzoate IM. In the eCG group, cows received the same treatment described for the control group but also received 400 UI of eCG at the time of device removal. In the TCR group, calves were separated from the cows for 56 hours after device removal. Ultrasound exams were performed every 24 hours after device removal until the time of ovulation and 12 days after ovulation to measure the size of the CL. On the same day as the CL measurement, blood was collected to determine the plasma P4 level. Statistical analyses were performed with a significance level of P ≤ 0.05. In cyclic cows, the presence of the CL at the beginning of protocol resulted in a smaller follicle diameter at the time of device removal (7.4 ± 0.3 mm in cows with CL vs. 8.9 ± 0.4 mm in cows without CL; P ¼ 0.03). All cows ovulated within 72 hours after device removal. Anestrous cows treated with eCG or TCR showed follicle diameter at fixed-timed artificial insemination (A-eCG 10.2 ± 0.3 and A-TCR 10.3 ± 0.5 mm) and follicular growth rate (A-eCG 1.5 ± 0.2 and A-TCR 1.3 ± 0.1 mm/day) similar to cyclic cows (C-eCG 11.0 ± 0.6 and C-TCR 12.0 ± 0.5 mm) and (C-eCG 1.4 ± 0.2 and C-TCR 1.6 ± 0.2 mm/day, respectively; P ≤ 0.05). Despite the similarities in CL size, the average P4 concentration was higher in the A-TCR (9.6 ± 1.4 ng/mL) than in the A-control (4.0 ± 1.0 ng/mL) and C-TCR (4.4 ± 1.0 ng/mL) groups (P < 0.05). From these results, we conclude that eCG treatment and TCR improved the fertility of anestrous cows by providing follicular growth rates and size of dominant follicles similar to cyclic cows. Additionally, TCR increases the plasma concentrations of P4 in anestrous cows

Temporal changes of CB1 cannabinoid receptor in the basal ganglia as a possible structure-specific plasticity process in 6-OHDA lesioned rats

The endocannabinoid system has been implicated in several neurobiological processes, including neurodegeneration, neuroprotection and neuronal plasticity. The CB1 cannabinoid receptors are abundantly expressed in the basal ganglia, the circuitry that is mostly affected in Parkinson’s Disease (PD). Some studies show variation of CB1 expression in basal ganglia in different animal models of PD, however the results are quite controversial, due to the differences in the procedures employed to induce the parkinsonism and the periods analyzed after the lesion. The present study evaluated the CB1 expression in four basal ganglia structures, namely striatum, external globus pallidus (EGP), internal globus pallidus (IGP) and substantia nigra pars reticulata (SNpr) of rats 1, 5, 10, 20, and 60 days after unilateral intrastriatal 6-hydroxydopamine injections, that causes retrograde dopaminergic degeneration. We also investigated tyrosine hydroxylase (TH), parvalbumin, calbindin and glutamic acid decarboxylase (GAD) expression to verify the status of dopaminergic and GABAergic systems. We observed a structure-specific modulation of CB1 expression at different periods after lesions. In general, there were no changes in the striatum, decreased CB1 in IGP and SNpr and increased CB1 in EGP, but this increase was not sustained over time. No changes in GAD and parvalbumin expression were observed in basal ganglia, whereas TH levels were decreased and the calbindin increased in striatum in short periods after lesion. We believe that the structure-specific variation of CB1 in basal ganglia in the 6-hydroxydopamine PD model could be related to a compensatory process involving the GABAergic transmission, which is impaired due to the lack of dopamine. Our data, therefore, suggest that the changes of CB1 and calbindin expression may represent a plasticity process in this PD model

Role of nitric oxide and endocannabinoids in synaptic plasticity in the perirhinal cortex and in visual recognition memory

Introduction and aims of the research Nitric oxide (NO) and endocannabinoids (eCBs) are major retrograde messengers, involved in synaptic plasticity (long-term potentiation, LTP, and long-term depression, LTD) in many brain areas (including hippocampus and neocortex), as well as in learning and memory processes. NO is synthesized by NO synthase (NOS) in response to increased cytosolic Ca2+ and mainly exerts its functions through soluble guanylate cyclase (sGC) and cGMP production. The main target of cGMP is the cGMP-dependent protein kinase (PKG). Activity-dependent release of eCBs in the CNS leads to the activation of the Gαi/o-coupled cannabinoid receptor 1 (CB1) at both glutamatergic and inhibitory synapses. The perirhinal cortex (Prh) is a multimodal associative cortex of the temporal lobe, critically involved in visual recognition memory. LTD is proposed to be the cellular correlate underlying this form of memory. Cholinergic neurotransmission has been shown to play a critical role in both visual recognition memory and LTD in Prh. Moreover, visual recognition memory is one of the main cognitive functions impaired in the early stages of Alzheimer’s disease. The main aim of my research was to investigate the role of NO and ECBs in synaptic plasticity in rat Prh and in visual recognition memory. Part of this research was dedicated to the study of synaptic transmission and plasticity in a murine model (Tg2576) of Alzheimer’s disease. Methods Field potential recordings. Extracellular field potential recordings were carried out in horizontal Prh slices from Sprague-Dawley or Dark Agouti juvenile (p21-35) rats. LTD was induced with a single train of 3000 pulses delivered at 5 Hz (10 min), or via bath application of carbachol (Cch; 50 μM) for 10 min. LTP was induced by theta-burst stimulation (TBS). In addition, input/output curves and 5Hz-LTD were carried out in Prh slices from 3 month-old Tg2576 mice and littermate controls. Behavioural experiments. The spontaneous novel object exploration task was performed in intra-Prh bilaterally cannulated adult Dark Agouti rats. Drugs or vehicle (saline) were directly infused into the Prh 15 min before training to verify the role of nNOS and CB1 in visual recognition memory acquisition. Object recognition memory was tested at 20 min and 24h after the end of the training phase. Results Electrophysiological experiments in Prh slices from juvenile rats showed that 5Hz-LTD is due to the activation of the NOS/sGC/PKG pathway, whereas Cch-LTD relies on NOS/sGC but not PKG activation. By contrast, NO does not appear to be involved in LTP in this preparation. Furthermore, I found that eCBs are involved in LTP induction, but not in basal synaptic transmission, 5Hz-LTD and Cch-LTD. Behavioural experiments demonstrated that the blockade of nNOS impairs rat visual recognition memory tested at 24 hours, but not at 20 min; however, the blockade of CB1 did not affect visual recognition memory acquisition tested at both time points specified. In three month-old Tg2576 mice, deficits in basal synaptic transmission and 5Hz-LTD were observed compared to littermate controls. Conclusions The results obtained in Prh slices from juvenile rats indicate that NO and CB1 play a role in the induction of LTD and LTP, respectively. These results are confirmed by the observation that nNOS, but not CB1, is involved in visual recognition memory acquisition. The preliminary results obtained in the murine model of Alzheimer’s disease indicate that deficits in synaptic transmission and plasticity occur very early in Prh; further investigations are required to characterize the molecular mechanisms underlying these deficits.

Cyclic alternating pattern in sleep and its relationship to creativity

Background/Objectives: Sleep has been shown to enhance creativity, but the reason for this enhancement is not entirely known. There are several different physiological states associated with sleep. In addition to rapid (REM) and non-rapid eye movement (NREM) sleep, NREM sleep can be broken down into Stages (1-4) that are characterized by the degree of EEG slow wave activity. In addition, during NREM sleep there are transient but cyclic alternating patterns (CAP) of EEG activity and these CAPs can also be divided into three subtypes (A1-A3) according to speed of the EEG waves. Differences in CAP ratios have been previously linked to cognitive performances. The purpose of this study was to learn the relationship CAP activity during sleep and creativity. Methods: The participants were 8 healthy young adults (4 women), who underwent 3 consecutive nights of polysomnographic recording and took the Abbreviated Torrance Test for Adults (ATTA) on the 2 and 3rd mornings after the recordings. Results: There were positive correlations between Stage 1 of NREM sleep and some measures of creativity such as fluency (R= .797; p=.029) and flexibility ( R=.43; p=.002), between Stage 4 of Non-REM sleep and originality (R= .779; p=.034) and a global measure of figural creativity (R= .758; p=.040). There was also a negative correlation between REM sleep and originality (R= -.827; p= .042) . During NREM sleep the CAP rate, which in young people is primarily the A1 subtype, also correlated with originality (R= .765; p =.038). Conclusions: NREM sleep is associated with low levels of cortical arousal and low cortical arousal may enhance the ability of people to access to the remote associations that are critical for creative innovations. In addition, A1 CAP activity reflects frontal activity and the frontal lobes are important for divergent thinking, also a critical aspect of creativity.

Plasticity in body and peripersonal space representations

A successful interaction with objects in the environment requires integrating information concerning object-location with the shape, dimension and position of body parts in space. The former information is coded in a multisensory representation of the space around the body, i.e. peripersonal space (PPS), whereas the latter is enabled by an online, constantly updated, action-orientated multisensory representation of the body (BR) that is critical for action. One of the critical features of these representations is that both PPS and BR are not fixed, but they dynamically change depending on different types of experience. In a series of experiment, I studied plastic properties of PPS and BR in humans. I have developed a series of methods to measure the boundaries of PPS representation (Chapter 4), to study its neural correlates (Chapter 3) and to assess BRs. These tasks have been used to study changes in PPS and BR following tool-use (Chapter 5), multisensory stimulation (Chapter 6), amputation and prosthesis implantation (Chapter 7) or social interaction (Chapter 8). I found that changes in the function (tool-use) and the structure (amputation and prosthesis implantation) of the physical body elongate or shrink both PPS and BR. Social context and social interaction also shape PPS representation. Such high degree of plasticity suggests that our sense of body in space is not given at once, but it is constantly constructed and adapted through experience.

Investigation of the lithium ion mobility in cyclic model compounds and their ion conducting properties

Efficient energy storage and conversion is playing a key role in overcoming the present and future challenges in energy supply. Batteries provide portable, electrochemical storage of green energy sources and potentially allow for a reduction of the dependence on fossil fuels, which is of great importance with respect to the issue of global warming. In view of both, energy density and energy drain, rechargeable lithium ion batteries outperform other present accumulator systems. However, despite great efforts over the last decades, the ideal electrolyte in terms of key characteristics such as capacity, cycle life, and most important reliable safety, has not yet been identified. rnrnSteps ahead in lithium ion battery technology require a fundamental understanding of lithium ion transport, salt association, and ion solvation within the electrolyte. Indeed, well-defined model compounds allow for systematic studies of molecular ion transport. Thus, in the present work, based on the concept of ‘immobilizing’ ion solvents, three main series with a cyclotriphosphazene (CTP), hexaphenylbenzene (HBP), and tetramethylcyclotetrasiloxane (TMS) scaffold were prepared. Lithium ion solvents, among others ethylene carbonate (EC), which has proven to fulfill together with pro-pylene carbonate safety and market concerns in commercial lithium ion batteries, were attached to the different cores via alkyl spacers of variable length.rnrnAll model compounds were fully characterized, pure and thermally stable up to at least 235 °C, covering the requested broad range of glass transition temperatures from -78.1 °C up to +6.2 °C. While the CTP models tend to rearrange at elevated temperatures over time, which questions the general stability of alkoxide related (poly)phosphazenes, both, the HPB and CTP based models show no evidence of core stacking. In particular the CTP derivatives represent good solvents for various lithium salts, exhibiting no significant differences in the ionic conductivity σ_dc and thus indicating comparable salt dissociation and rather independent motion of cations and ions.rnrnIn general, temperature-dependent bulk ionic conductivities investigated via impedance spectroscopy follow a William-Landel-Ferry (WLF) type behavior. Modifications of the alkyl spacer length were shown to influence ionic conductivities only in combination to changes in glass transition temperatures. Though the glass transition temperatures of the blends are low, their conductivities are only in the range of typical polymer electrolytes. The highest σ_dc obtained at ambient temperatures was 6.0 x 10-6 S•cm-1, strongly suggesting a rather tight coordination of the lithium ions to the solvating 2-oxo-1,3-dioxolane moieties, supported by the increased σ_dc values for the oligo(ethylene oxide) based analogues.rnrnFurther insights into the mechanism of lithium ion dynamics were derived from 7Li and 13C Solid- State NMR investigations. While localized ion motion was probed by i.e. 7Li spin-lattice relaxation measurements with apparent activation energies E_a of 20 to 40 kJ/mol, long-range macroscopic transport was monitored by Pulsed-Field Gradient (PFG) NMR, providing an E_a of 61 kJ/mol. The latter is in good agreement with the values determined from bulk conductivity data, indicating the major contribution of ion transport was only detected by PFG NMR. However, the μm-diffusion is rather slow, emphasizing the strong lithium coordination to the carbonyl oxygens, which hampers sufficient ion conductivities and suggests exploring ‘softer’ solvating moieties in future electrolytes.rn