Necessity to Measure PCBs and Organochlorine Pesticide Concentrations in Human Umbilical Cords for Fetal Exposure Assessment

Three types of tissue samples—umbilical cord (UC), umbilical cord serum (CS), and maternal serum (MS)—have often been used to assess fetal exposure to chemicals. In order to know the relationship of contamination between mothers and fetuses, we measured persistent chemicals in comparable sets of the three tissue samples. Also, we analyzed the association between the chemicals in maternal and fetal tissues to know which tissue is the best sample for fetal exposure assessment. On a wet basis, the chemical concentrations were of the order MS > CS > UC, except for some chemicals such as cis-chlordane and endosulfan. On a lipid basis, the concentrations in UC were nearly equal or often higher than in MS, but the concentrations in CS were usually lower than in others. Hexachlorocyclohexanes and penta-, hexa-, and heptachlorinated biphenyls showed an association between the concentrations in UC versus MS, and UC versus CS. These chemicals also showed high correlation coefficients between the chemical concentrations in UC of first babies and maternal age. These chemicals were closely related to each other when grouped on the basis of their concentrations using cluster analysis. In conclusion, we insist that UC is the best sample to assess fetal contamination status of persistent chemicals. There is a possibility that the assessment based on the contamination levels in CS result in an underestimation

Neuroradiological and neurofunctional examinations for the patients with 22q11.2 deletion

Since neuroradiological features of patients with 22q11.2 deletion syndrome are not well-understood, examinations using functional imaging were performed in this study. Brain magnetic resonance imaging(MRI) and 1H-magnetic resonance spectroscopy(MRS) were performed using a clinical 3-tesla MR imager in 4 patients with 22q11.2 deletion syndrome (2 boys and 2 girls; 2~6 years.) and 20 age- and sex-matched healthy control subjects. Furthermore, interictal 123I- iomazenil (IMZ) single photon emission computed tomography(SPECT) was examined in two of the four patients. Among 4 patients with 22q11.2 deletion syndrome, 2 patients showed polymicrogyria and 1 patient showed agyria. Those patients with brain malformations also showed abnormal brain artery and decreased accumulation of IMZ in 123I-IMZ SPECT. Although all 4 patients showed epileptic discharges in electroencephalogram(EEG), one patient with polymicrogyria had no seizure episode. Decreases in γ-aminobutyric acid(GABA) corresponding to the areas of polymicrogyria and/or epileptic discharges in EEG were shown in all patients except for the patient with agyria. Although consistent evidence was not seen in patients with 22q11.2 deletion syndrome in this study, brain malformations and disturbances of the GABAergic nervous system would be underlying mechanisms of the neurodevelopmental abnormalities in this syndrome

Issues for application of virtual microscopy to cytoscreening, perspectives based on questionnaire to Japanese cytotechnologists

To clarify the issues associated with the applications of virtual microscopy to the daily cytology slide screening, we conducted a survey at a slide conference of cytology. The survey was conducted specifically to the Japanese cytology technologists who use microscopes on a routine basis. Virtual slides (VS) were prepared from cytology slides using NanoZoomer (Hamamatsu Photonics, Japan), which is capable of adjusting focus on any part of the slide. A total of ten layers were scanned from the same slides, with 2 micrometer intervals. To simulate the cytology slide screening, no marker points were created. The total data volume of six slides was approximately 25 Giga Bytes. The slides were stored on the Windows 2003 Server, and were made accessible on the web to the cytology technologists. Most cytotechnologists answered "Satisfied" or "Acceptable" to the VS resolution and drawing speed, and "Dissatisfied" to the operation speed. To the ten layered focus, an answer "insufficient" was slightly more frequent than the answer "sufficient", while no one answered "fewer is acceptable" or "no need for depth". As for the use of cytology slide screening, answers "usable, but requires effort" and "not usable" were about equal in number. In a Japanese cytology meeting, a unique VS system has been used in slide conferences with markings to the discussion point for years. Therefore, Japanese cytotechnologists are relatively well accustomed to the use of VS, and the survey results showed that they regarded VS more positively than we expected. Currently, VS has the acceptable resolution and drawing speed even on the web. Most cytotechnologists regard the focusing capability crucial for cytology slide screening, but the consequential enlargement of data size, longer scanning time, and slower drawing speed are the issues that are yet to be resolved

Evaluation of the GABAergic nervous system in autistic brain : 123I-iomazenil SPECT study

Purpose: To evaluate the GABAA receptor in the autistic brain, we performed 123I-IMZ SPECT in patients with ASD. We compared 123I-IMZ SPECT abnormalities in patients who showed intellectual disturbance or focal epileptic discharge on EEG to those in patients without such findings. Subjects and methods: The subjects consisted of 24 patients with ASD (mean age, 7.3±3.5years), including 9 with autistic disorder (mean age, 7.0±3.7years) and 15 with Asperger’s disorder (mean age, 7.5±3.2years). We used 10 non-symptomatic partial epilepsy patients (mean age, 7.8±3.6years) without intellectual delay as a control group. For an objective evaluation of the 123I-IMZ SPECT results, we performed an SEE (Stereotactic Extraction Estimation) analysis to describe the decrease in accumulation in each brain lobule numerically. Results In the comparison of the ASD group and the control group, there was a dramatic decrease in the accumulation of 123I-IMZ in the superior and medial frontal cortex. In the group with intellectual impairment and focal epileptic discharge on EEG, the decrease in accumulation in the superior and medial frontal cortex was greater than that in the group without these findings. Conclusion The present results suggest that disturbance of the GABAergic nervous system may contribute to the pathophysiology and aggravation of ASD, since the accumulation of 123I-IMZ was decreased in the superior and medial frontal cortex, which is considered to be associated with inference of the thoughts, feelings, and intentions of others (Theory of Mind)

Study of parameters in focus simulation functions of virtual slide

As a special function of Virtual Slide (VS) for thick specimens like cytology slides, multilayer (Z-stack) simulated focus and focus fusion were introduced. From the standpoint of surgical pathologist, the optimum parameters for multilayer focus simulation were examined. First, minimal thickness of the layer was checked by measuring thickness of small cells counting the number of the layers that come into focus. Then the optimal number of layers to scan, total thickness, was tried. Small-sized cell nuclei showed around 2μm or less thickness. As minimal thickness of one layer for focus simulation, less than 2 μm is required. Papillary cell mass of urothelial carcinoma, aspiration cytology specimen of breast or thyroid, and uterine cervical smear showed different optimal thickness. Cells piling up more than 4 to 5 layer are difficult to make close up observation. Total 15 (to 30) μm thick scan was enough for most specimens. The “focus fusion” image is single layer image synthesized from multiple layer images. Several layer thicknesses were examined, and there was negligible difference between the focus fusion image synthesized from 0.25 and 1μm thick layers. In the focus fusion image synthesized from 3μm thick layers, some cells not to come into focus. The “focus fusion” seems to contain all the cells in one plane, and easy for screening. To emphasize the existence of myoepithelial cells in fibroadenoma of breast, or to clarify the 3-dimensional tissue structure, multilayer image was better. From our results, 10 layers with 1.5μm thick each provide sufficient information in most specimens

ジヘイショウ ノ シンダン チリョウ サイゼンセン

In this paper we review the pathophysiology of autism.1）The amygdala theory of autismThe network of neural regions that comprise the social brain includes the amygdala. There isa reduction in volume of amygdala in children with autism. The concentration of N-acetylaspartateis also decreased in amygdala of autistic brain. The amygdala is therefore proposed to be one ofseveral neural regions that are abnormal in autism.2）Mirror neuron dysfunction in autismChildren with autism underwent fMRI while imitating and observing emotional expressions.They showed no mirror neuron activity in the inferior frontal gyrus（pars opercularis）. Notably,activity in this area was inversely related to symptom severity in the social domain, suggestingthat a dysfunctional mirror neuron system may underlie the social deficits observed in autism

RIM1 confers sustained activity and neurotransmitter vesicle anchoring to presynaptic Ca2+ channels.

International audienceThe molecular organization of presynaptic active zones is important for the neurotransmitter release that is triggered by depolarization-induced Ca2+ influx. Here, we demonstrate a previously unknown interaction between two components of the presynaptic active zone, RIM1 and voltage-dependent Ca2+ channels (VDCCs), that controls neurotransmitter release in mammalian neurons. RIM1 associated with VDCC beta-subunits via its C terminus to markedly suppress voltage-dependent inactivation among different neuronal VDCCs. Consistently, in pheochromocytoma neuroendocrine PC12 cells, acetylcholine release was significantly potentiated by the full-length and C-terminal RIM1 constructs, but membrane docking of vesicles was enhanced only by the full-length RIM1. The beta construct beta-AID dominant negative, which disrupts the RIM1-beta association, accelerated the inactivation of native VDCC currents, suppressed vesicle docking and acetylcholine release in PC12 cells, and inhibited glutamate release in cultured cerebellar neurons. Thus, RIM1 association with beta in the presynaptic active zone supports release via two distinct mechanisms: sustaining Ca2+ influx through inhibition of channel inactivation, and anchoring neurotransmitter-containing vesicles in the vicinity of VDCCs

Function of the frontal lobe in autistic individuals: a proton magnetic resonance spectroscopic study

Purpose. In this investigation, we studied differences in chemical metabolites in certain brain regions between autistic patients and normal control subjects. Methods. Proton magnetic resonance spectroscopy (1H-MRS) was used to evaluate functional activity in these regions. Specific regions studied were right and left dorsolateral prefrontal cortex(DLPFC) and the anterior cingulated cortex(ACC). Results. In the ACC, the N-acetylaspartate(NAA)/creatine/phosphocreatine(Cr) ratio in autistic patients (n=31) was significantly lower than that in control subjects (n=28). The decrease in the NAA/Cr ratio for the ACC was much greater in the group with worst social ability. NAA/Cr for the left DLPFC and social ability of autistic patients also correlated well. Furthermore, NAA/Cr for the left DLPFC in the group with intelligence quotient (IQ) below 50 was significantly less than in controls. NAA/Cr for the right DLPFC in autistic patients was not decreased compared to controls, and did not correlate with IQ or social ability. Conclusions. These findings suggest neuronal dysfunction in the ACC and left DLPFC in autism, and also a relationship between social disability and metabolic dysfunction in these regions. Dysfunction in the ACC and the left DLPFC may contribute to the pathogenesis of autism

Transient Receptor Potential 1 Regulates Capacitative Ca2+ Entry and Ca2+ Release from Endoplasmic Reticulum in B Lymphocytes〉

Capacitative Ca2+ entry (CCE) activated by release/depletion of Ca2+ from internal stores represents a major Ca2+ influx mechanism in lymphocytes and other nonexcitable cells. Despite the importance of CCE in antigen-mediated lymphocyte activation, molecular components constituting this mechanism remain elusive. Here we demonstrate that genetic disruption of transient receptor potential (TRP)1 significantly attenuates both Ca2+ release-activated Ca2+ currents and inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release from endoplasmic reticulum (ER) in DT40 B cells. As a consequence, B cell antigen receptor–mediated Ca2+ oscillations and NF-AT activation are reduced in TRP1-deficient cells. Thus, our results suggest that CCE channels, whose formation involves TRP1 as an important component, modulate IP3 receptor function, thereby enhancing functional coupling between the ER and plasma membrane in transduction of intracellular Ca2+ signaling in B lymphocytes

Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(c) (Sanofi-Aventis Farmacêutica Ltda, Brazil, reference product) and Levaquin(c) (Janssen-Cilag Farmacêutica Ltda, Brazil, test product) was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters Cmax, Tmax, Kel, T1/2el, AUC0-t and AUC0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI) for the ratio of Cmax, AUC0-t and AUC0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for Cmax, AUC0-t and AUC0-inf were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(c) and Levaquin(c) are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies.A bioequivalência média de duas formulações de levofloxacino disponíveis no Brasil, Tavanic(c) (Sanofi-Aventis Farmacêutica Ltda, Brasil, produto referência) e Levaquin(c) (Janssen-Cilag Farmacêutica Ltda, Brasil, produto teste) foi determinada por meio da realização de ensaio aleatório, aberto, cruzado, com dois períodos e duas sequências, em 26 voluntários sadios em condições de jejum. Amostras de sangue dos voluntários foram obtidas ao longo de um período de 48 horas após administração de dose única de 500 mg de levofloxacino. As concentrações plasmáticas do fármaco foram determinadas por método cromatográfico validado. Os parâmetros farmacocinéticos Cmax, Tmax, Kel, T1/2el, AUC0-t e AUC0-inf foram calculados por análise não compartimental. A bioequivalência foi determinada pelo cálculo de intervalos de confiança 90% (IC 90%) para as razões entre os valores de Cmax, AUC0-t e AUC0-inf obtidos para os produtos teste e referência, usando dados transformados logaritmicamente. A tolerabilidade foi avaliada pelo acompanhamento dos sinais vitais e resultados de exames laboratoriais, por consultas e por relato espontâneo dos voluntários. ICs 90% para Cmax, AUC0-t e AUC0-inf foram 92.1% - 108.2%, 90.7% - 98.0%, e 94.8% - 100.0%, respectivamente. Os eventos adversos observados foram náusea e cefaleia. Concluiu-se que os produtos Tavanic(c) e Levaquin(c) são bioequivalentes, uma vez que os ICs 90% estão dentro da faixa de 80%-125% proposta pelas agências reguladora