Modulation of Th1- and Th2-type immune response in infant mouse after prenatal exposure to volatile organic compound

胎児期､乳児期は化学物質に対して高感受性の時期であるとも云われており､多種多様な化学物質による子供の健康影響とそのメカニズムを把握することは生体機能の正常な発達の観点から重要と考えられている。本研究では低濃度トルエンの胎児期曝露が仔マウスの全身および局所でのTh1/Th2免疫応答に及ぼす影響についてグラム陽性菌細胞壁成分ペプチドグリカン(PGN; peptidoglycan)との併用, 非併用下で検討した。その結果､5,50ppm トルエンのみもしくはPGN刺激との併用曝露は血中や脾臓においてTh1及びTh2型免疫応答に関係するいくつかの免疫パラメーター(総Ig抗体サブクラスの産生レベルや転写因子T-bet, GATA-3, Foxp3のmRNA発現等)をかく乱することを明らかした

The pupil in glaucoma

Glaucoma is the most common preventable cause of blind-registration in elderly Western populations. Case-finding is crucial for the prevention of blindness. There is no single test that can reliably diagnose glaucoma, especially early cases. The relative afferent pupillary detect (RAPD) is known to be sensitive in the detection of optic nerve pathology. The clinical swinging flash light test is well used for this purpose. However, the test requires skill and careful interpretation, and the sensitivity of the test is limited to ≥0.3 log units of relative pupillomotor deficit. Some of the newly-built commercially available pupillometers measure the pupil parameters with accuracy. These instruments have mainly been used in the area of refractive surgery. This thesis considers the applicability of the commercially available pupillometer P3000 to the diagnosis of glaucoma. In this thesis a pupillometer (P3000) was calibrated before the stimulus parameters were tested for their best suitability for the RAPD test. The stimulus and outcome parameters were optimised. The chosen stimulus configuration (0.4s-1.6s on-off combination) produced repeatable results. The eyes were dark adapted only for 30 seconds before each test sequence for practical use in clinics. The pupillographic RAPD was calculated from the pupil constriction amplitudes calibrated in response to 3 levels of light stimulus. Data was collected on normal and glaucomatous subjects. There was no significant diurnal variation in the RAPD noted for both cohorts and the immediate repeatability was high. The final test was used in a methods comparison study to detect glaucoma against the gold standard of clinical diagnosis. The area under the Receiver Operating Characteristic curve for the detection of all grades of unilateral or bilateral glaucoma was in the region of 0.81 for the cohort of 101 normal and 117 glaucoma patients. Pupillometry may be helpful as an adjunctive test in the detection of glaucoma

In utero and Lactational Exposure to Acetamiprid Induces Abnormalities in Socio-Sexual and Anxiety-Related Behaviors of Male Mice

Neonicotinoid, a widely-used pesticide group designed to selectively bind to insect nicotinic acetylcholine receptors, were considered to be relatively safe for mammalian species. However, it has been found to activate vertebrate nicotinic acetylcholine receptors than ever anticipated, and could be toxic to the mammalian brain. In the present study, we evaluated the developmental neurotoxicity of acetamiprid (ACE), one of the most-widely used neonicotinoid, in C57BL/6J mice whose mothers were administered ACE via gavage at doses of either 0 mg/kg (control), 1.0 mg/kg (low-dose) or 10.0 mg/kg (high-dose) from gestational day 6 to lactation day 21. As possible endpoints, a battery of behavior tests, socio-sexual and anxiety-related behaviors, as well as testosterone level and the number of vasopressin-immunoreactive cells in the paraventricular nucleus of the hypothalamus were examined. In addition, behavioral flexibility was assessed for mice in a group-housed environment using an IntelliCage, a fully automated mouse behavioral analysis system. In adult male mice exposed to ACE at both low and high doses, significant reduction of anxiety level was found in the light-dark transition test. Males in the low-dose group also showed a significant increase in sexual and aggressive behaviors. In contrast, neither the anxiety nor the sexual behavior of females was altered. No impairments in testosterone level, the number of vasopressin-immunoreactive cells, and behavioral flexibility were detected in either sex. These results suggest the possibility that in utero and lactational ACE exposure interferes with the development of the neural circuits required for executing socio-sexual and anxiety-related behaviors in male mice specifically

Nanoparticles and Neurotoxicity

Humans are exposed to nanoparticles (NPs; diameter < 100 nm) from ambient air and certain workplaces. There are two main types of NPs; combustion-derived NPs (e.g., particulate matters, diesel exhaust particles, welding fumes) and manufactured or engineered NPs (e.g., titanium dioxide, carbon black, carbon nanotubes, silver, zinc oxide, copper oxide). Recently, there have been increasing reports indicating that inhaled NPs can reach the brain and may be associated with neurodegeneration. It is necessary to evaluate the potential toxic effects of NPs on brain because most of the neurobehavioral disorders may be of environmental origin. This review highlights studies on both combustion-derived NP- and manufactured or engineered NP-induced neuroinflammation, oxidative stress, and gene expression, as well as the possible mechanism of these effects in animal models and in humans

Leprosy post-exposure prophylaxis with single-dose rifampicin

_Objective:_ Leprosy post-exposure prophylaxis with single-dose rifampicin (SDRPEP) has proven effective and feasible, and is recommended by WHO since 2018. This SDR-PEP toolkit was developed through the experience of the leprosy postexposure prophylaxis (LPEP) programme. It has been designed to facilitate and standardise the implementation of contact tracing and SDR-PEP administration in regions and countries that start the intervention. _Results:_ Four tools were developed, incorporating the current evidence for SDRPEP and the methods and learnings from the LPEP project in eight countries. (1) th

Leprosy post-exposure prophylaxis with single-dose rifampicin (LPEP): an international feasibility programme

Background Innovative approaches are required for leprosy control to reduce cases and curb transmission of Mycobacterium leprae. Early case detection, contact screening, and chemoprophylaxis are the most promising tools. We aimed to generate evidence on the feasibility of integrating contact tracing and administration of single-dose rifampicin (SDR) into routine leprosy control activities. Methods The leprosy post-exposure prophylaxis (LPEP) programme was an international, multicentre feasibility study implemented within the leprosy control programmes of Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka, and Tanzania. LPEP explored the feasibility of combining three key interventions: systematically tracing contacts of individuals newly diagnosed with leprosy; screening the traced contacts for leprosy; and administering SDR to eligible contacts. Outcomes were assessed in terms of number of contacts traced, screened, and SDR administration rates. Findings Between Jan 1, 2015, and Aug 1, 2019, LPEP enrolled 9170 index patients and listed 179 769 contacts, of whom 174782 (97·2%) were successfully traced and screened. Of those screened, 22 854 (13·1%) were excluded from SDR mainly because of health reasons and age. Among those excluded, 810 were confirmed as new patients (46 per 10 000 contacts screened). Among the eligible screened contacts, 1182 (0·7%) refused prophylactic treatment with SDR. Overall, SDR was administered to 151 928 (86·9%) screened contacts. No serious adverse events were reported. Interpretation Post-exposure prophylaxis with SDR is safe; can be integrated into different leprosy control programmes with minimal additional efforts once contact tracing has been established; and is generally well accepted by index patients, their contacts, and health-care workers. The programme has also invigorated local leprosy control through the availability of a prophylactic intervention; therefore,

Early Exposure to Intermediate-Frequency Magnetic Fields Alters Brain Biomarkers without Histopathological Changes in Adult Mice

Recently we have reported that intermediate-frequency magnetic field (IF-MF) exposure transiently altered the mRNA expression levels of memory function-related genes in the hippocampi of adult male mice. However, the effects of IF-MF exposure during brain development on neurological biomarkers have not yet been clarified. In the present study, we investigated the effect of IF-MF exposure during development on neurological and immunological markers in the mouse hippocampus in 3- and 7-week-old male mice. Pregnant C57BL/6J mice were exposed to IF-MF (21 kHz, 3.8 mT) for one hour per day from organogenesis period day 7 to 17. At adolescence, some IF-MF-exposed mice were further divided into exposure, recovery, and sham-exposure groups. The adolescent-exposure groups were exposed again to IF-MF from postnatal day 27 to 48. The expression of mRNA in the hippocampi was examined using a real-time RT-PCR method, and microglia activation was examined by immunohistochemical analysis. The expression levels of NR1 and NR2B as well as transcription factors (CaMKIV, CREB1), inflammatory mediators (COX2, IL-1 b,TNF-α), and the oxidative stress marker heme-oxygenase (HO)-1 were significantly increased in the IF-MF-exposed mice, compared with the control group, in the 7-week-old mice, but not in the 3-week-old mice. Microglia activation was not different between the control and other groups. This study provides the first evidence that early exposure to IF-MF reversibly affects the NMDA receptor, its related signaling pathways, and inflammatory mediators in the hippocampus of young adult mice; these changes are transient and recover after termination of exposure without histopathological changes

Image compression using conjugate symmetric sequency-ordered complex hadamard transform [CS-SCHT]

In this report, image compression using a new transform called Sequency-ordered Complex Hadamard Transform (CS-SCHT) is presented with simulation results and computer based implementation demo. This compression method is specifically introduced for reducing computational complexity, archiving reasonably high-quality images of scanned documents with lowering cost for future real-time implementation. Transform matrix of the CS-SCHT possesses sequency ordering and its spectrum is a conjugated symmetric. Comparison of energy compaction capabilities of commonly used transforms such as discrete cosine transforms (DCT), sequence ordered Walsh transform (SOWT) and CS-SCHT are given. Computational load of the CS-SCHT is also compared against the above mentioned commonly used transforms. Derivation and proof of its properties are discussed and analyzed with applications in image compression. Mean-square-error (MSE) and Peak Signal to Noise Ratio (PSNR) performances are considered as standard measures of image quality. Simulation results from MATLAB and low level programming language C# proved that the CS-SCHT is promising to be developed in such application.Bachelor of Engineerin