The combined treatment of preimplantation mouse embryos in vitro with cadmium (CdSO4, CdF2) and X-rays

The influence of cadmium (up to 10^?4 M), fluoride (up to 10^?4 M), and X-rays (up to 18.8 Gy) on different variables of preimplantation mouse embryos in vitro has been examined. The agents were applied either singly or in combination (0.94 Gy X-rays +3×10^?7 M CdSO₄ or CdF₂; 0.94 Gy X-rays +3×10^?6 M CdSO₄ or CdF₂). The following variables were determined:

1. the microscopic visible development until 144 h post conceptionem (=144 h p.c.),
2. the average cell numbers (48 h p.c., 56 h p.c., 72 h p.c., 96 h p.c., 120 h p.c., 144 h p.c.),
3. the number of micronuclei (72 h p.c.),
4. the distribution of cell nuclei within the cell cycle (72 h p.c.).

Nearly all results of the combination experiments correspond to the sum of the single effects. Only two values (out of about 40) significantly exceed the value obtained after addition of the single effects; both values lie within the envelope of additivity.     

First experiences in using a new ultrasound mode and ultrasound contrast agent in the diagnosis of blunt renal trauma: a feasibility study in an animal model

RATIONALE AND OBJECTIVES: To evaluate the diagnostic value of the new ultrasound mode "wide-band harmonic" (WBH) using an ultrasound contrast agent in blunt renal trauma in an animal model. METHODS: A defined blunt renal trauma was induced in 10 rabbits according to published standards. Ultrasound (B-mode, color and power Doppler, WBH) was performed before and after trauma, with and without using a contrast agent (Levovist). Ultrasound features were compared with histologic findings. RESULTS: In 2 of the 10 rabbits, three focal renal intraparenchymal lesions with diameters ranging from 1.0 to 1.8 mm were found that could be identified only using WBH with contrast. Six of the 10 rabbits developed a subcapsular hematoma with a thickness of up to 1.5 mm, which was identified by conventional B-mode as well as WBH. Histologic workup confirmed these findings of intraparenchymal hematomas and did not reveal further lesions. CONCLUSIONS: Only 20% of the experimental subjects developed parenchymal lesions with diameters of 1.0 mm or larger. All these lesions were identified only using WBH. These results indicate the potential to use WBH plus contrast for the diagnosis of blunt renal trauma.     

Generation of complement C3 and expression of cell membrane complement inhibitory proteins by human bronchial epithelium cell line

BACKGROUND: The interrelationship between human airway epithelium and complement proteins may affect airway defence, airway function, and airway epithelial integrity. A study was undertaken to determine (1) whether unstimulated human bronchial epithelium generates complement proteins and expresses cell membrane complement inhibitory proteins (CIP) and (2) whether stimulation by proinflammatory cytokines affects the generation of complement and expression of cell membrane CIP by these cells. METHODS: Human bronchial epithelium cell line BEAS-2B was cultured in a serum-free medium. Cells were incubated with and without proinflammatory cytokines to assess unstimulated and stimulated generation of complement C3, C1q and C5 (by ELISA), and to examine the expression of cell membrane CIP decay accelerating factor (DAF; CD55), membrane cofactor protein (MCP; CD46), and CD59 (protectin) by flow cytometry analysis. RESULTS: Unstimulated human bronchial epithelial cell line BEAS-2B in serum-free medium generates complement C3 (mean 32 ng/10(6) cells/72 h, range 18-52) but not C1q and C5, and expresses cell membrane DAF, MCP, and CD59. Interleukin (IL)-1alpha (100 U/ml/72 h) and tumour necrosis factor (TNF-alpha; 1000 U/ml/72 h) increased generation of C3 up to a mean of 78% and 138%, respectively, above C3 generation by unstimulated cells. DAF was the only cell membrane CIP affected by cytokine stimulation. Interferon (IFN)-gamma (10 U/ml/72 h) and TNF-alpha (1000 U/ml/72 h) increased DAF expression up to a mean of 116% and 45%, respectively, above that in unstimulated cells. MCP and CD59 expression was not consistently affected by IL-1alpha, TNF-alpha, or IFN-gamma. CONCLUSIONS: Local generation of complement C3 and expression of cell membrane CIP by human bronchial epithelium and its modulation by proinflammatory cytokines might be an additional regulatory mechanism of local airway defence and may affect airway function and epithelial integrity in health and disease.     

Antiprotozoal activities of new bicyclo[2.2.2]octan-2-imines and esters of bicyclo[2.2.2]octan-2-ols.

Several bicyclo[2.2.2]octan-2-imines and esters of bicyclo[2.2.2]octan-2-ols were prepared. Their antitrypanosomal and antiplasmodial activities against Trypanosoma brucei rhodesiense (STIB 900) and the K1 strain of Plasmodium falciparum (resistant to chloroquine and pyrimethamine) were determined using microplate assays. Two of the synthesized bicyclo[2.2.2]octan-2-one 4'-phenylthiosemicarbazones showed the highest antitrypanosomal activity (IC(50)<0.3 microM) of the so far prepared 4-amino-6,7-diarylbicyclo[2.2.2]octane derivatives, but they are distinctly less active than suramine (IC(50)=0.0075 microM). Most of the 4'-phenylthiosemicarbazones and a single bicyclo[2.2.2]octan-2-yl benzoate exhibit attractive antimalarial activity (IC(50)=0.23-0.72 microM). Two bicyclooctanone oximes are even as active as chloroquine (IC(50)=0.08-0.15 microM, chloroquine: IC(50)=0.12 microM against sensitive strains).     

Comparison of artifacts produced from carbon fiber and titanium alloy needles at 1.5 T MR imaging

A novel coaxial carbon fiber-based biopsy needle set was investigated in phantom experiments and compared with a commercially available, magnetic resonance (MR)-compatible titanium alloy set using MR imaging at 1.5 T. Image artifacts observed with different MR sequences were assessed. It was found that the carbon fibers produced distinctly smaller image artifacts compared with the titanium needle. Depending on the type of MR sequence, the relative range of artifact size ratios between the carbon and titanium needles was between 0.7 (spin-echo sequence) and 0.4 (gradient-echo sequence) with the needles oriented perpendicular to the main magnetic field. Carbon fiber composites are promising materials for the design and construction of MR-compatible instruments.     

凌晨3:00皮下注射短效胰岛素治疗2型糖尿病黎明现象

目的:观察应用凌晨3:00皮下注射短效胰岛素治疗2型糖尿病黎明现象的疗效。方法:对40例有黎明现象的2型糖尿病患者,使用短效胰岛素凌晨3:00注射4~6U。抽取肘静脉血测定空腹血糖(FPG)及早餐后2h血糖(2hPG),免疫比浊法测定糖化血红蛋白(HbA1c),比较治疗前后上述指标变化。结果:本组患者FPG从治疗前(9.5±1.6)mmol/L下降至(6.0±0.4)mmol/L,治疗2个月后仍保持为(5.6±0.4)mmol/L;2hPG从治疗前(13.8±0.8)mmol/L下降至(7.4±0.4)mmol/L,在治疗2个月后保持为(7.9±0.3)mmol/L;FPG和2hPG与治疗前比较,均具有显著性差异(P<0.01)。治疗2个月后,HbA1c从治疗前(8.3±0.6)%下降至(6.5±0.3)%,与治疗前比较,有显著性差异(P<0.01)。结论:短效胰岛素强化治疗黎明现象具有快速稳定的降血糖和降糖化血红蛋白作用。     

Right-hemisphere dominance for the processing of sound-source lateralization.

Cortical processing of change in direction of a perceived sound source was investigated in 12 human subjects using whole-head magnetoencephalography. The German word "da" was presented either with or without 0.7 msec interaural time delays to create the impression of right- or left-lateralized or midline sources, respectively. Midline stimuli served as standards, and lateralized stimuli served as deviants in a mismatch paradigm. Two symmetrically linked dipoles fitted to the mismatch fields showed stronger moments in the hemisphere contralateral to the side of the deviant. The right dipole displayed equal latencies to both left and right deviants, whereas left dipole latencies were longer for ipsilateral than contralateral deviants. Frequency analysis between 20-70 Hz and statistical probability mapping revealed increased induced gamma-band activity at 53+/-2.5 Hz to both types of deviants. Right deviants elicited spectral amplitude enhancements in this frequency range, peaking at latencies of 160 and 240 msec. These effects were localized bilaterally over the angular gyri and posterior temporal regions. Coherence analysis suggested the existence of two separate interhemispheric networks. For left-lateralized deviants, both spectral amplitude enhancements at 110 and 220 msec and coherence increases were restricted to the right hemisphere. In conclusion, both mismatch dipole latencies at the supratemporal plane and gamma-band activity in posterior parietotemporal areas suggested a right hemisphere engagement in the processing of bidirectional sound-source shifts. In contrast, left-hemisphere regions responded predominantly to contralateral events. These findings may help to elucidate phenomena such as unilateral auditory neglect.     

Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity.

PURPOSE: Myeloid suppressor (Gr-1(+)/CD11b(+)) cells accumulate in the spleens of tumor-bearing mice where they contribute to immunosuppression by inhibiting the function of CD8(+) T cells and by promoting tumor angiogenesis. Elimination of these myeloid suppressor cells may thus significantly improve antitumor responses and enhance effects of cancer immunotherapy, although to date few practical options exist. EXPERIMENTAL DESIGN: The effect of the chemotherapy drug gemcitabine on the number of (Gr-1(+)/CD11b(+)) cells in the spleens of animals bearing large tumors derived from five cancer lines grown in both C57Bl/6 and BALB/c mice was analyzed. Suppressive activity of splenocytes from gemcitabine-treated and control animals was measured in natural killer (NK) cell lysis and Winn assays. The impact of myeloid suppressor cell activity was determined in an immunogene therapy model using an adenovirus expressing IFN-beta. RESULTS: This study shows that the chemotherapeutic drug gemcitabine, given at a dose similar to the equivalent dose used in patients, was able to dramatically and specifically reduce the number of myeloid suppressor cells found in the spleens of animals bearing large tumors with no significant reductions in CD4(+) T cells, CD8(+) T cells, NK cells, macrophages, or B cells. The loss of myeloid suppressor cells was accompanied by an increase in the antitumor activity of CD8(+) T cells and activated NK cells. Combining gemcitabine with cytokine immunogene therapy using IFN-beta markedly enhanced antitumor efficacy. CONCLUSIONS: These results suggest that gemcitabine may be a practical strategy for the reduction of myeloid suppressor cells and should be evaluated in conjunction with a variety of immunotherapy approaches.     

Systematic Evidence Map for Over One Hundred and Fifty Per- and Polyfluoroalkyl Substances (PFAS)

Background: Per- and polyfluoroalkyl substances (PFAS) are a large class of synthetic (man-made) chemicals widely used in consumer products and industrial processes. Thousands of distinct PFAS exist in commerce. The 2019 U.S. Environmental Protection Agency (U.S. EPA) Per- and Polyfluoroalkyl Substances (PFAS) Action Plan outlines a multiprogram national research plan to address the challenge of PFAS. One component of this strategy involves the use of systematic evidence map (SEM) approaches to characterize the evidence base for hundreds of PFAS.Objective: SEM methods were used to summarize available epidemiological and animal bioassay evidence for a set of ∼150 PFAS that were prioritized in 2019 by the U.S. EPA’s Center for Computational Toxicology and Exposure (CCTE) for in vitro toxicity and toxicokinetic assay testing.Methods: Systematic review methods were used to identify and screen literature using manual review and machine-learning software. The Populations, Exposures, Comparators, and Outcomes (PECO) criteria were kept broad to identify mammalian animal bioassay and epidemiological studies that could inform human hazard identification. A variety of supplemental content was also tracked, including information on in vitro model systems; exposure measurement–only studies in humans; and absorption, distribution, metabolism, and excretion (ADME). Animal bioassay and epidemiology studies meeting PECO criteria were summarized with respect to study design, and health system(s) were assessed. Because animal bioassay studies with ≥21-d exposure duration (or reproductive/developmental study design) were most useful to CCTE analyses, these studies underwent study evaluation and detailed data extraction. All data extraction is publicly available online as interactive visuals with downloadable metadata.Results: More than 40,000 studies were identified from scientific databases. Screening processes identified 44 animal and 148 epidemiology studies from the peer-reviewed literature and 95 animal and 50 epidemiology studies from gray literature that met PECO criteria. Epidemiological evidence (available for 15 PFAS) mostly assessed the reproductive, endocrine, developmental, metabolic, cardiovascular, and immune systems. Animal evidence (available for 40 PFAS) commonly assessed effects in the reproductive, developmental, urinary, immunological, and hepatic systems. Overall, 45 PFAS had evidence across animal and epidemiology data streams.Discussion: Many of the ∼150 PFAS were data poor. Epidemiological and animal evidence were lacking for most of the PFAS included in our search. By disseminating this information, we hope to facilitate additional assessment work by providing the initial scoping literature survey and identifying key research needs. Future research on data-poor PFAS will help support a more complete understanding of the potential health effects from PFAS exposures. https://doi.org/10.1289/EHP10343