A gold speciation that adds a second layer to synergistic gold-copper toxicity in Cupriavidus metallidurans.

The metal-resistant bacterium Cupriavidus metallidurans occurs in metal-rich environments. In auriferous soils, the bacterium is challenged by a mixture of copper ions and gold complexes, which exert synergistic toxicity. The previously used, self-made Au(III) solution caused a synergistic toxicity of copper and gold that was based on the inhibition of the CupA-mediated efflux of cytoplasmic Cu(I) by Au(I) in this cellular compartment. In this publication, the response of the bacterium to gold and copper was investigated by using a commercially available Au(III) solution instead of the self-made solution. The new solution was five times more toxic than the previously used one. Increased toxicity was accompanied by greater accumulation of gold atoms by the cells. The contribution of copper resistance determinants to the commercially available Au(III) solution and synergistic gold-copper toxicity was studied using single- and multiple-deletion mutants. The commercially available Au(III) solution inhibited periplasmic Cu(I) homeostasis, which is required for the allocation of copper ions to copper-dependent proteins in this compartment. The presence of the gene for the periplasmic Cu(I) and Au(I) oxidase, CopA, decreased the cellular copper and gold content. Transcriptional reporter gene fusions showed that up-regulation of gig, encoding a minor contributor to copper resistance, was strictly glutathione dependent. Glutathione was also required to resist synergistic gold-copper toxicity. The new data indicated a second layer of synergistic copper-gold toxicity caused by the commercial Au(III) solution, inhibition of the periplasmic copper homeostasis in addition to the cytoplasmic one.IMPORTANCEWhen living in auriferous soils, Cupriavidus metallidurans is not only confronted with synergistic toxicity of copper ions and gold complexes but also by different gold species. A previously used gold solution made by using aqua regia resulted in the formation of periplasmic gold nanoparticles, and the cells were protected against gold toxicity by the periplasmic Cu(I) and Au(I) oxidase CopA. To understand the role of different gold species in the environment, another Au(III) solution was commercially acquired. This compound was more toxic due to a higher accumulation of gold atoms by the cells and inhibition of periplasmic Cu(I) homeostasis. Thus, the geo-biochemical conditions might influence Au(III) speciation. The resulting Au(III) species may subsequently interact in different ways with C. metallidurans and its copper homeostasis system in the cytoplasm and periplasm. This study reveals that the geochemical conditions may decide whether bacteria are able to form gold nanoparticles or not.

Photocontrolled Reversible Amyloid Fibril Formation of Parathyroid Hormone-Derived Peptides.

Peptide fibrillization is crucial in biological processes such as amyloid-related diseases and hormone storage, involving complex transitions between folded, unfolded, and aggregated states. We here employ light to induce reversible transitions between aggregated and nonaggregated states of a peptide, linked to the parathyroid hormone (PTH). The artificial light-switch 3-{[(4-aminomethyl)phenyl]diazenyl}benzoic acid (AMPB) is embedded into a segment of PTH, the peptide PTH25-37, to control aggregation, revealing position-dependent effects. Through in silico design, synthesis, and experimental validation of 11 novel PTH25-37-derived peptides, we predict and confirm the amyloid-forming capabilities of the AMPB-containing peptides. Quantum-chemical studies shed light on the photoswitching mechanism. Solid-state NMR studies suggest that ß-strands are aligned parallel in fibrils of PTH25-37, while in one of the AMPB-containing peptides, ß-strands are antiparallel. Simulations further highlight the significance of π-π interactions in the latter. This multifaceted approach enabled the identification of a peptide that can undergo repeated phototriggered transitions between fibrillated and defibrillated states, as demonstrated by different spectroscopic techniques. With this strategy, we unlock the potential to manipulate PTH to reversibly switch between active and inactive aggregated states, representing the first observation of a photostimulus-responsive hormone.

The specific expression patterns of sensory neuron membrane proteins are retained throughout the development of the desert locust Schistocerca gregaria.

The desert locust Schistocerca gregaria detects odorants through olfactory sensory neurons (OSNs) that are surrounded by non-neuronal support cells (SCs). OSNs and SCs are housed in cuticle structures, named sensilla found abundantly on the antenna in all developmental stages of the hemimetabolic insect. In insects, multiple proteins expressed by OSNs and SCs are indicated to play a pivotal role in the detection of odorants. This includes insect-specific members of the CD36 family of lipid receptors and transporters called sensory neuron membrane proteins (SNMPs). While the distribution pattern of the SNMP1 and SNMP2 subtypes in OSNs and SCs across different sensilla types has been elucidated for the adult S. gregaria antenna, their localization in cells and sensilla of different developmental stages is unclear. Here, we determined the SNMP1 and SNMP2 expression topography on the antenna of the first, third and fifth instar nymphs. Through FIHC experiments we found that in all developmental stages SNMP1 is expressed in OSNs and SCs of the trichoid and basiconic sensilla while SNMP2 is restricted to the SCs of the basiconic and coeloconic sensilla thus resembling the adult arrangement. Our results demonstrate that both SNMP types have defined cell- and sensilla-specific distribution patterns established already in the first instar nymphs and retained into the adult stage. This conserved expression topography underlines the importance of SNMP1 and SNMP2 in olfactory processes throughout the development of the desert locust.

Psychopharmacological treatment of mood and anxiety disorders during pregnancy.

Many women with psychiatric disorders want to become mothers and only a minority seek advise prior to becoming pregnant. In those women, in whom pregnancy can be planned, the decision, if a medication is required for stabilisation and which one to choose if this is the case, is easier to make than in women in whom pregnancy occurs unplanned. The physician has to weigh the risk that a relapse of the psychiatric disorder during pregnancy poses to the foetus against the reproductive risk of psychotropic drugs. This presentation is intended to assist in understanding the general principles of pharmacotherapy during pregnancy as well as the morphological, perinatal and neurobehavioural toxicity of antidepressants, antipsychotics, benzodiazepines and mood stabilisers.

Perimenopause and Postmenopause - Diagnosis and Interventions. Guideline of the DGGG and OEGGG (S3-Level, AWMF Registry Number 015-062, September 2020).

Aim The aim of the interdisciplinary S3-guideline Perimenopause and Postmenopause - Diagnosis and Interventions is to provide help to physicians as they inform women about the physiological changes which occur at this stage of life and the treatment options. The guideline should serve as a basis for decisions taken during routine medical care. This short version lists the statements and recommendations given in the long version of the guideline together with the evidence levels, the level of recommendation, and the strength of consensus. Methods The statements and recommendations are largely based on methodologically high-quality publications. The literature was evaluated by experts and mandate holders using evidence-based medicine (EbM) criteria. The search for evidence was carried out by the Essen Research Institute for Medical Management (EsFoMed). To some extent, this guideline also draws on an evaluation of the evidence used in the NICE guideline on Menopause and the S3-guidelines of the AWMF and has adapted parts of these guidelines. Recommendations Recommendations are given for the following subjects: diagnosis and therapeutic interventions for perimenopausal and postmenopausal women, urogynecology, cardiovascular disease, osteoporosis, dementia, depression, mood swings, hormone therapy and cancer risk, as well as primary ovarian insufficiency.

Altered representation of expected value in the orbitofrontal cortex in mania.

OBJECTIVE: Increased responsiveness to appetitive and reduced responsiveness to aversive anticipatory cues may be associated with dysfunction of the brain reward system in mania. Here we studied neural correlates of gain and loss expectation in mania using functional magnetic resonance imaging (fMRI). METHOD: Fifteen manic patients and 26 matched healthy control individuals performed a monetary incentive delay task, during which subjects anticipated to win or lose a varying amount of money. Varying both magnitude and valence (win, loss) of anticipatory cues allowed us to isolate the effects of magnitude, valence and expected value (magnitude-by-valence interaction). RESULTS: Response times and total gain amount did not differ significantly between groups. FMRI data indicated that the ventral striatum responded according to cued incentive magnitude in both groups, and this effect did not significantly differ between groups. However, a significant group difference was observed for expected value representation in the left lateral orbitofrontal cortex (OFC; BA 11 and 47). In this region, patients showed increasing BOLD responses during expectation of increasing gain and decreasing responses during expectation of increasing loss, while healthy subjects tended to show the inverse effect. In seven patients retested after remission OFC responses adapted to the response pattern of healthy controls. CONCLUSIONS: The observed alterations are consistent with a state-related affective processing bias during the expectation of gains and losses which may contribute to clinical features of mania, such as the enhanced motivation for seeking rewards and the underestimation of risks and potential punishments.

[Bipolar disorder, pregnancy and the postpartum--risks and possibilities of pharmacotherapy]. / Psychopharmaka in Schwangerschaft und Stillzeit--Risiken und Möglichkeiten bei Frauen mit einer bipolaren affektiven Störung.

Pregnancy and the postpartum are times of increased risk for women with bipolar disorder to develop mood episodes, especially depressions that may require pharmacotherapy. If mood stabilizing agents are discontinued prior or due to pregnancy, the risk for relapse increases dramatically. On the other hand, there is no psychotropic drug that is completely risk-free for the unborn. Some mood stabilizing medications are teratogenic, others can cause severe perinatal complications. Thus, the decision whether to treat the pregnant women with psychotropic drugs is difficult to make. In this paper, the reproductive risks of mood stabilizing agents, antidepressants, neuroleptics and benzodiazepines for the fetus are reviewed. During the postpartum period severe mood disorders can occur. The signs and symptoms of these disorders are reviewed and therapeutic strategies are discussed.

Sanctioning of Illegal and Dangerous Ruck Cleanouts During the 2018 Super Rugby Competition.

Rugby is a high contact sport that results in many injuries. The majority of injuries at senior elite levels result from contact phases during match-play. It is estimated that 10% of all match injuries are associated with the ruck in professional and community rugby. Surveillance of legal and illegal ruck cleanouts and the sanctions imposed by the on-field referees will help identify whether referees are actually enforcing the law according to the laws of the game, which will consequently contribute to the creation and implementation of further injury prevention strategies. Players should play the game in accordance with the laws of the game and be mindful of their own safety and that of others. Coaches and trainers of the game have the responsibility to ensure that players are prepared in a manner that comply with the World Rugby (WR) laws of the game and safe practices. Laws and law amendments are fundamental to the development of sport and introduced for a variety of reasons. The aim of this study was to investigate the rate of sanctioning of illegal and dangerous ruck cleanouts during the 2018 Super Rugby competition by using Nacsport Basic+ video software; 120 round robin matches from the 2018 Super Rugby competition were coded and analyzed. The analysis of the intra reliability showed an almost perfect (>0.95) agreement between all the performance indicators. In total, 22,281 ruck cleanouts were coded of which 9% (n = 2111) were illegal ruck cleanouts and 93% were not sanctioned by the referees; 57% (1087 out of 1953) of the illegal ruck cleanouts not sanctioned by the referees were deemed dangerous. The majority of dangerous illegal ruck cleanouts not sanctioned by the referees were "shoulder charge" (88%, n = 280), "neck roll" (86%, n = 100), and "contact above the shoulder" (81%, n = 201). To aid injury prevention efforts in rugby, future research studies should investigate why on-field referees are not sanctioning all illegal and dangerous ruck cleanouts according to WR Laws of the Game.

Odor-related brain hyper-reactivity in euthymic bipolar disorder: An fMRI and ERP study.

Previous studies on olfactory function in patients with bipolar disorder (BD) are limited and contradictory. The current study aimed to comprehensively analyze the olfactory function of patients with euthymic BD using psychophysical, electrophysiological and neuroimaging techniques. Twenty-one patients with BD in remission and 20 healthy controls were tested with the "Sniffin' Sticks" olfactory test. Block-design fMRI data to a pleasant and an unpleasant stimulus were acquired while recording intensity and hedonic ratings. Olfactory event-related potentials (OERP) to the same stimuli were additionally recorded. Results show no differences between patients and healthy controls in terms of self-rated olfactory function and tested olfactory domains (odor threshold, discrimination or identification) (p>0.05). Compared to healthy controls, patients showed an increased fMRI activation in multiple cortical and subcortical regions as a response to olfactory stimulation, as well as larger amplitudes of OERPs regardless of the hedonic valence of the odor. All in all, patients with euthymic BD showed a stronger central responsiveness to odorous stimuli in fMRI and OERPs despite of normal psychophysical results, indicating the probable existence of an odor-related over-reactive brain network in the remission phase of BD.

The effects of maternal dietary supplementation of cholecalciferol (vitamin D3) and 25(OH)D3 on sow and progeny performance.

A total of 69 sows (DNA Line 200 × 400) and their progeny were used to determine if feeding a combination of vitamin D3 and 25(OH)D3 influences neonatal and sow vitamin D status, muscle fiber morphometrics at birth and weaning, and subsequent growth performance. Within 3 d of breeding, sows were allotted to one of three dietary treatments fortified with 1,500 IU/kg vitamin D3 (CON), 500 IU/kg vitamin D3 + 25 µg/kg 25(OH)D3 (DL), or 1,500 IU/kg vitamin D3 + 50 µg/kg 25(OH)D3 (DH). When pigs were sacrificed at birth, there were no treatment effects for all fiber morphometric measures (P > 0.170), except primary fiber number and the ratio of secondary to primary muscle fibers (P < 0.016). Pigs from CON fed sows had fewer primary fibers than pigs from sows fed the DH treatment (P = 0.014), with pigs from sows fed DL treatment not differing from either (P > 0.104). Pigs from CON and DL fed sows had a greater secondary to primary muscle fiber ratio compared to pigs from DH sows (P < 0.022) but did not differ from each other (P = 0.994). There were treatment × time interactions for all sow and pig serum metabolites (P < 0.001). Therefore, treatment means were compared within the time period. At all time periods, sow serum 25(OH)D3 concentrations differed for all treatments with the magnitude of difference largest at weaning (P < 0.011), where serum 25(OH)D3 concentration was always the greatest when sows were fed the DH diet. At birth, piglets from DH fed sows had greater serum 25(OH)D3 concentrations than piglets from sows fed the DL treatment (P = 0.003), with piglets from sows fed CON treatment not differing from either (P > 0.061). At weaning, serum concentrations of 25(OH)D3 in piglets from all sow treatments were different (P < 0.001), with the greatest concentration in piglets from DH sows, followed by CON, and followed by DL. There were no treatment × time interactions for any of the metabolites measured in milk and no treatment or time main effects for 24,25(OH)2D3 concentration (P > 0.068). Colostrum collected within 12 h of parturition contained less (P = 0.001) 25(OH)D3 than milk collected on day 21 of lactation. Regardless of time, concentrations of 25(OH)D3 in milk were different (P < 0.030), with the largest 25(OH)D3 concentration from DH fed sows, followed by DL, and then CON. In conclusion, combining vitamin D3 and 25(OH)D3 in the maternal diet improves the vitamin D status of the dam and progeny and it increases primary muscle fiber number at birth.

Neuroleptic-induced parkinsonism is associated with olfactory dysfunction.

OBJECTIVE: There is increasing evidence for olfactory deficits in patients with extrapyramidal disorders, but little is known about their occurrence in patients with drug-induced extrapyramidal symptoms (EPS). The present study was performed to investigate olfactory function in depressed patients with drug-induced parkinsonism under treatment with D2-blocking neuroleptic drugs compared to depressed controls on similar neuroleptic dose without EPS (no-EPS), and neuroleptic-naive depressed controls (no-NL). METHODS: A total of 79 depressed patients with (N = 59) and without psychotic features (N = 20) were included in the study. Psychotic patients were treated with D2 blocking neuroleptic drugs. Of the neuroleptic-treated patients, 15 developed EPS. In all patients psychophysical olfactory testing was performed using "Sniffin' Sticks" which included assessment of odor thresholds for phenylethylalcohol (PEA), odor identification, and odor discrimination. RESULTS: Patients in the EPS group had significantly lower olfactory scores than patients in the no-EPS or no-NL groups. Patients in the no-NL and no-EPS groups were not significantly different from each other in terms of olfactory function. Using partial correlations controlling for the patients' age, significant correlations were observed for EPS patients between severity of EPS and odor thresholds and odor identification, but not for odor discrimination. This indicated that olfactory function decreased with increasing severity of EPS symptoms. CONCLUSIONS: Our data show that olfactory deficits may be drug-induced in patients with primary affective disorder with a sensitivity toward developing EPS.

Planar chromatographic screening and quantification of coumarin in food, confirmed by mass spectrometry.

A sensitive quantitative screening of coumarin in 43 commercially available cinnamons and cinnamon-containing foods was developed via HPTLC. Complex samples like cinnamon, tea, breakfast cereals, milk rice, jam, cinnamon stars and buns were extracted with methanol only. Separation was performed on silica gel with a mixture of n-hexane, ethyl acetate and ammonia. The specific detection via derivatization with an ethanolic potassium hydroxide solution resulted in fluorescent coumarin zones, measured at 365/>400nm after stabilization. Limits of detection and quantification were 200 and 400pg/band, respectively. Over all different sample types, the contents ranged from 0.3 to 5129mg/kg with a mean repeatability and mean intermediate precision of 4% each. HPTLC-MS of selected zones, eluted via the TLC-MS Interface into MS, confirmed the identity of coumarin. Effect-directed detection as bioanalytical tool for risk assessment showed coumarin to be active against Aliivibrio fischeri bacteria down to 100ng/band.

Fingerprinting and characterization of anthocyanins in 94 colored wheat varieties and blue aleurone and purple pericarp wheat crosses.

Colored wheat varieties and crosses were analyzed to figure out their anthocyanin profiles, and thus, their potential as health-related food. After method development, the obtained 94 anthocyanin fingerprints allowed the clear differentiation of the blue aleurone and purple pericarp genotypes as well as their breeding lines. The method was trimmed so that the complete analysis of the whole grain flour including sample preparation of up to 20 samples on one plate took less than 3 h (<9 min per sample) and total costs including sample preparation were <1.0 Euro/sample. Sample preparation of the complex wheat matrix was reduced to a minimum (only acidified methanol extraction of the ground whole wheat grain). Separation was well achieved on amino phases with a mixture of ethyl acetate, 2-butanone, water and formic acid. It was superior to the separation on either normal or reversed phases and more robust with regard to intrinsic pH variances of the sample extracts. Pattern recognition of anthocyanins was simply performed by visual detection (the image), a key feature of high-performance thin-layer chromatography. Wheat varieties and crosses with higher anthocyanin contents were easily selectable, and thus, successfully made out. Prominent anthocyanin zones were characterized by electrospray ionization mass spectrometry. Their sugar moiety was characterized via methanolysis and compared with the sugars available freely in the whole wheat grain. The developed profiling is a fast and efficient screening tool with option for quantification or identification on the same HPTLC plate.

Male reproductive system and spermatogenesis of Limodromus assimilis (Paykull 1790).

Based on advanced light and electron microscopy, we describe the male reproductive system and sperm development of Limodromus assimilis. The genital tract consists of pairs of uni-follicular testes, spermatic ducts with diverticula regions, seminal vesicles, accessory glands, an unpaired ejaculatory duct and an aedeagus containing an internal sac equipped with sclerotic scales. Based on their morphology, we draw conclusions about their functions. After spermatogenesis within the follicle, the spermatozoa become released from the sperm cysts. The single spermatozoa move into the diverticula of the vasa deferentia I. Here, they become attached to central rods (spermatostyles), forming secondary conjugates (spermiozeugmata). The coordinated flagella movement of the conjugates possibly improves sperm velocity. Using super-resolution microscopy, we identified highly condensed reticulate chromatin in the lancet-shaped spermatozoa heads and the mitochondrial derivates of the flagella, likely formed by genomic and mitochondrial DNA, respectively. The results show, for the first time, sperm bundle formation in a Platynini species mainly corresponding to that found in Pterostichini species.

Risk and resilience markers in bipolar disorder: brain responses to emotional challenge in bipolar patients and their healthy siblings.

OBJECTIVE: The authors previously identified depression-specific differences in brain responses to an emotional challenge in patients with bipolar and unipolar mood disorder. In this study, potential markers of bipolar risk and resilience were examined in a new cohort of lithium-responsive bipolar patients and their healthy siblings. METHOD: Changes in regional cerebral blood flow (rCBF) were measured with [(15)O]water positron emission tomography after induction of transient sadness in nine euthymic lithium responders and nine healthy siblings. The patterns of change in these groups were compared, and then they were contrasted with previous findings on bipolar responders to valproate. RESULTS: Common to all three groups with induced sadness were rCBF increases in the dorsal/rostral anterior cingulate and anterior insula and decreases in the orbitofrontal and inferior temporal cortices. Distinguishing the groups were decreases in the medial frontal cortex in the patients but an increase in this region in the siblings. DISCUSSION: Common changes with emotional challenge were identified in bipolar patients and their healthy siblings. These were not seen previously in healthy subjects without a family history of mood disorder, suggesting a potential marker of bipolar risk. The siblings' unique increases in the medial frontal cortex appear to identify a compensatory response in this at-risk group, as this pattern was not seen previously in healthy subjects without depression risk factors. This differential change pattern in patients and their siblings highlights the role of the anterior cingulate and medial frontal regions in mediating resiliency and vulnerability in bipolar disorder families.

Associação entre hábitos orais e má oclusão com problemas respiratórios em escolares de 5 anos / Association between oral habits and malocclusion with respiratory problems in 5-year-old schoolchildren

Introdução Toda má oclusão apresenta origem multifatorial, e dentre os fatores que a desencadeiam estão os hábitos. O surgimento de um hábito pode estar relacionado com o emocional, o fisiológico ou com o aprendizado condicionado do indivíduo. Objetivo Analisar as relações entre hábitos e más oclusões associado a problemas respiratórios em escolares de 5 anos. Material e método Foi realizado um estudo transversal com uma amostra de 753 crianças pertencentes à rede municipal de ensino da cidade de Araraquara, SP. Foram realizados exames clínicos para avaliação da má oclusão (Foster & Hamilton), além de aplicado questionários aos pais para avaliação de condição socioeconômica e demográfica, qualidade de vida relacionada à saúde bucal (ECOHIS) e hábitos. A análise dos dados foi feita pela análise bivariada por teste qui-quadrado seguida de modelo de regressão logística múltipla considerando nível de significância de 5%. Resultado A prevalência de crianças com problemas respiratórios e/ou alergias foi de 46,9%, com má oclusão foi de 58,7% e com algum tipo de hábito oral deletério foi de 12,0%. Apresentaram mais chance de ter problemas respiratórios e/ou alergias crianças do sexo masculino (1,40 vezes mais) e crianças com algum hábito oral deletério (1,95 vezes mais). Conclusão Observou-se que apresentaram maior chance de problemas respiratórios e/ou alergias as crianças do sexo masculino, crianças com algum hábito oral deletério e que apresentavam bruxismo.

Introduction All malocclusion has a multifactorial origin, and among the factors that trigger it are the habits. The appearance of a habit can be related to the emotional, physiological or conditioned learning of the individual. Objective Evaluate the relationship between habits and malocclusions associated with respiratory problems in 5-year-old students. Material and method A cross-sectional study were carried out with a sample of 753 children belonging to the municipal education network of the city of Araraquara-SP. Clinical exams were performed for malocclusion evaluation (Foster & Hamilton), applying questionnaires to the parents for evaluation of socioeconomic and demographic condition, oral health related quality of life (ECOHIS) and habits. Data analysis was performed by bivariate analysis using chi-square test followed by multiple logistic regression model considering 5% significance level. Result The prevalence of children with respiratory problems and/or allergies was 46.9%, with malocclusion was 58.7% and with some type of deleterious oral habit was 12.0%. Male children were 1.40 times more likely to present respiratory problems or allergies and children with some deleterious oral habits were 1.95 times more likely to present respiratory problems or allergies. Conclusion It was observed that male children, children that presented deleterious oral habits, and children with bruxism are more likely to have respiratory problems and/or allergies.

Comparison and characterization of soybean and sunflower lecithins used for chocolate production by high-performance thin-layer chromatography with fluorescence detection and electrospray mass spectrometry.

The scarce availability of nongenetically modified soybeans on the world market represents a growing problem for food manufacturers. Hence, in this study the effects of substituting soybean with sunflower lecithin were investigated with regard to chocolate production. The glycerophospholipid pattern of the different lecithin samples was investigated by high-performance thin-layer chromatography fluorescence detection (HPTLC-FLD) and by HPTLC-positive ion electrospray ionization mass spectrometry (ESI(+)-MS) via the TLC-MS Interface and by scanning HPTLC-matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOFMS). Especially, the contents of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were of interest due to the influencing effects of these two glycerophospholipids on the rheological parameters of chocolate production. The lecithin substitution led to only slight differences in the rheological parameters of milk and dark chocolate. Limits of detection (LODs) and limits of quantification (LOQs) of seven glycerophospholipids were studied for three detection modes. Mean LODs ranged from 8 to 40 mg/kg for HPTLC-FLD and, using a single-quadrupole MS, from 10 to 280 mg/kg for HPTLC-ESI(+)-MS as well as from 15 to 310 mg/kg for HPTLC-FLD-ESI(+)-MS recorded after derivatization with the primuline reagent.

State and trait influences on mood regulation in bipolar disorder: blood flow differences with an acute mood challenge.

BACKGROUND: Even in remission, patients with bipolar disorder (BD) remain sensitive to external stressors that can trigger new episodes. Imitating such stressors by the controlled transient exposure to an emotional stimulus may help to identify brain regions modulating this sensitivity. METHODS: Transient sadness was induced in 9 euthymic and in 11 depressed subjects with BD. Regional blood flow (rCBF) changes were measured using (15)O-water positron emission tomography. RESULTS: Common changes in both groups were increased rCBF in anterior insula and cerebellum and decreased rCBF in dorsal-ventral-medial frontal cortex, posterior cingulate, inferior parietal, and temporal cortices. Decreases in dorsal ventral medial frontal cortices occurred in both groups, but subjects in remission showed a greater magnitude of change. Unique to remitted subjects with BD were rCBF increases in dorsal anterior cingulate and in premotor cortex. Lateral prefrontal rCBF decreases were unique to depressed subjects with BD. At baseline, remitted subjects showed a unique increase in dorsal anterior cingulate and orbitofrontal cortex. CONCLUSIONS: Common rCBF changes in remitted and depressed subjects identifies potential sites of disease vulnerability. Unique cingulate and orbitofrontal changes both at baseline and with induced sadness seen in the absence of prefrontal rCBF decreases may identify regional interactions important to the euthymic state in this population.

Relevance of the catatonic syndrome to the mixed manic episode.

BACKGROUND: Catatonic symptoms have been associated with mixed mania in the older psychiatric literature, however, to date no systematic studies have been performed to assess their frequency in these patients. METHOD: Ninety-nine patients with bipolar disorder manic or mixed episode were assessed for the presence of catatonia. RESULTS: Thirty-nine patients fulfilled criteria for mixed mania of whom 24 were catatonic. Among the patients with pure mania, only three were catatonic. Eighteen catatonic patients with mixed mania required admission to the acute care unit (ACU). LIMITATIONS: Our findings only apply to severely ill patients with mixed mania who require ACU admission. Nevertheless, it is important to know, that the likelihood of overlooking catatonia in less severely ill patients with mixed mania is low and that it does not need to be routinely assessed on a general ward. CONCLUSIONS: Catatonia is frequent in mania and linked to the mixed episode. Catatonia in mixed mania is likely to be found among the severely ill group of patients with mixed mania, who require emergency treatment.