Paradoxical sleep-promoting effects of brain extract from paradoxical sleep-deprived rats

Brain extract was obtained from whole brains of donor rats following four days of paradoxical sleep deprivation (PSD). Intraperitoneal injection of this brain extract in normal (i.e., not pretreated) recipient rats led to a significant increase of paradoxical sleep (PS) which was beginning at the third hour postinjection and still present on the day after treatment. Both PS episode number and PS episode duration were increased by the PSD extract, whereas slow-wave sleep was not influenced. Brain extract of nondeprived control rats, on the other hand, had no significant effects. In the present experiments, an extract volume obtained from two donor brains was transferred to one recipient. Compared to our earlier investigations (one donor brain/one recipient) this higher "dose" of PSD extract exerted a more pronounced and prolonged effect. These results support the idea that some PS-inducing factor(s) accumulating in the brain during PS deprivation may be involved in the regulation of paradoxical sleep.     

Effects of Zinc Exposure on Earthworms, Lumbricus terrestris, in an Artificial Soil

Earthworms have the potential to act as trophic links for pollutants that accumulate in urban soils. However, many pollutants may act as micronutrients at low concentrations and toxins at higher concentration. When pollutants are also micronutrients, bioaccumulations may initially increase trophic transfer as pollutant concentration increase, but at higher levels toxic effects may limit population size and the potential for trophic transfer. We found support for this model among earthworms exposed to a range of soil Zn levels. Worms showed increasing bioaccumulation of Zn with increasing Zn soil concentrations, but at higher Zn levels worm growth rates decreased.     

Tagesperiodische Schwankungen der cancerostatischen Wirkungsstärke von N-Oxyd-Lost beim Ehrlich-Ascites-Carcinom der Maus

Zusammenfassung Der Wirkungsgrad des Mitomens (N-Oxyd-Lost) auf das Ehrlich-Ascites-Carcinom der Maus zeigt deutliche Tagesschwankungen: In den frühen Abendstunden vor dem Maximum der Mitoseaktivität verabreicht, wirkt das Präparat nur schwach, in den frühen Morgenstunden vor dem Minimum der Mitoseaktivität verabfolgt, wirkt es stark. Der tageszeitlich verschiedene Wirkungsgrad kommt nicht nur in Unterschieden der überlebensrate, sondern auch in Unterschieden der Ascitesmenge zum Ausdruck und ist statistisch signifikant. Die festgestellte tagesabhängige Wirksamkeit steht mit dem allgemein angenommenen Wirkungsmechanismus des Mitomens als sog. Ruhekerngift gut in Einklang.

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Summary The effectiveness of the mitomen (mustard-N-oxide) on the Ehrlich ascites carcinoma of the mouse shows distinct daily fluctuations: If it is given in the early evening hours before the maximum mitotic activity it acts only weakly. If administered in the early morning hours before the minimum of mitotic activity it acts intensely. The differences in effectiveness during the day are made evident not only from the variations in the rate of survival, but also from the differences in the extent of ascites. They prove to be statistically significant. The daily fluctuations in the effectiveness as ascertained is in accordance with the generally assumed mechanism of the mitomen as a so-called poison of the resting nucleus.

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Interlaboratory studies with a proposed patch test design to evaluate the irritation potential of surfactants

Background: Development of cosmetic products and household detergents necessitates comparative study designs to assess the skin tolerance of products. In initial tests, the epicutaneous patch test for irritation is widely used. Objectives: This study was conducted to develop a protocol that would facilitate a comparison of results obtained when tests are conducted by different laboratories. Methods:‘In‐house’ and standardized patch test protocols were used to assess irritation potentials of surfactant‐based products in intra‐ and interlaboratory studies using defined surfactant samples. Results: The various in‐house protocols tested did not consistently produce equivalent results. In order to develop a study design that yields comparable results, various factors were identified and adjusted. The standardized study protocol includes occlusive application of 70 µl of the test substance to the back of 30 subjects, defined reading times and schemes, assessments based mainly on erythema, and inclusion of sodium laureth sulfate and sodium dodecyl sulfate as positive controls as well as water as a negative control. Conclusions: Use of the standardized protocol and training of assessors improved the reliability and consistency of results whereby the irritation potentials of the references and test samples were ranked similarly by the laboratories.     

Headache induced by a nitric oxide donor (nitroglycerin) responds to sumatriptan. A human model for development of migraine drugs

Experimental "vascular" headache in humans may be used in characterizing new migraine drugs. The effects of sumatriptan on nitroglycerin-(NTG)-induced headache and arterial responses were therefore studied. Following a double-blind randomized crossover design, 10 healthy volunteers received sumatriptan 6 mg s.c. or placebo succeeded by 20 min NTG (0.12 mg/kg/min) infusion. Headache was rated on a 10 points scale. Temporal and radial artery diameters and velocity in the middle cerebral artery (MCA) were measured with ultrasound. Sumatriptan reduced the NTG-induced headache, median score 1.5 versus 4 after placebo ( p <0.01) and decreased temporal and radial artery diameters 75±3 and 86±3% of baseline respectively ( p <0.05), Blood velocity in the MCA was unaffected. The NTG model may prove to be a valuable tool in the development of future migraine drugs. The results suggest that NTG headache in non-migraineurs may share mechanisms with migraine headache.     

Left aortic arch, retro-esophageal aortic segment, right descending aorta and right patent ductus arteriosus--a very rare "vascular ring" malformation

A vascular ring formed by a left aortic arch, a retro-esophageal segment, a right descending aorta and right-sided ductus or ligamentum arteriosum is a very rare anomaly up to now; only 16 cases have been reported in the literature. This report presents the case of an infant suffering from the symptoms of airway and esophageal compression, who was successfully operated on for this anomaly at the age of 5 months. The diagnosis was established by means of esophagogram and angiography. Diagnostic criteria and guidelines for therapy are discussed.     

16层螺旋CT血管造影对冠状动脉狭窄的评价

目的:分析16层螺旋CT血管造影(MSCTA)无创性评价冠状动脉(冠脉)狭窄的价值.方法:80例临床初诊疑为冠心病,既往无冠脉成形术和搭桥术史的患者,行冠脉16层MSCTA后(其中9例在CT扫描前心率超过80次/min的患者应用了β受体阻滞剂),回顾性重建心电门控轴位图像,并分别采用容积成像、多平面重建、曲面重建、最大密度投影等后处理方法,对所有冠脉及其分支进行重建,统计可供临床评价的、管径≥1.5 mm的冠脉段,以选择性冠脉造影(SCA)为标准,对比分析MSCTA诊断冠脉显著性狭窄(管腔平均直径缩小>50%)的准确性.结果:94%(989/1056)的冠脉节段和94%(290/310)的冠脉主支可供评价,(6%)67/1056段不能评价的主要原因分别为:心脏运动伪影39段,致密钙化20段和管腔显影不良8段.除外不能评价的冠脉,按节段和主支分类,与SCA相比,MSCTA诊断冠脉显著性狭窄的差异无统计学意义,其敏感性、特异性、阳性和阴性预期值分别为93%、99%、87%、99%和95%、98%、91%及99%.结论:在患者心率<80次/min时,16层MSCTA即可获得较好的图像质量用于评价冠脉并判断其狭窄程度,是一种值得临床医生信赖的检查冠脉有无狭窄的无创伤性方法.     

The RAR-RXR as well as the RXR-RXR pathway is involved in signaling growth inhibition of human CD34+ erythroid progenitor cells

Previous studies have shown that retinoic acid (RA), similar to tumor necrosis factor-alpha (TNF-alpha), can act as a bifunctional regulator of the growth of bone marrow progenitors, in that it can stimulate granulocyte-macrophage colony-stimulating factor (GM-CSF)- or interleukin-3 (IL-3)-induced GM colony formation, but potently inhibit G-CSF-induced growth. The present study, using highly enriched human CD34+ as well as Lin- murine bone marrow progenitor cells, demonstrates a potent inhibitory effect of 9-cis-RA on burst-forming unit-erythroid (BFU-E) colony formation regardless of the cytokine stimulating growth. Specifically, 9-cis-RA potently inhibited the growth of BFU-E response to erythropoietin (Epo) (100%), stem cell factor (SCF) + Epo (92%), IL- 3 + Epo (97%), IL-4 + Epo (88%), and IL-9 + Epo (100%). Erythroid colony growth was also inhibited when CD34+ progenitors were seeded at one cell per well, suggesting a direct action of RA. Using synthetic ligands to retinoic acid receptors (RARs) and retinoid X receptors (RXRs) that selectively bind and activate RAR-RXR or RXR-RXR dimers, respectively, we dissected the involvement of the two retinoid response pathways in the regulation of normal myeloid and erythroid progenitor cell growth. Transactivation studies showed that both the RAR (Ro 13- 7410) and RXR (Ro 25-6603 and Ro 25-7386) ligands were highly selective at 100 nmol/L. At this concentration, Ro 13-7410 potently inhibited G- CSF-stimulated myeloid as well as SCF + Epo-induced erythroid colony growth. At the same concentration, Ro 25-6603 and Ro 25-7386 had little or no effect on G-CSF-induced colony formation, whereas they inhibited 75% and 53%, respectively, of SCF + Epo-stimulated BFU-E colony growth. Thus, the RAR-RXR response pathway can signal growth inhibition of normal bone marrow myeloid and erythroid progenitor cells. In addition, we demonstrate a unique involvement of the RXR-RXR pathway in mediating growth inhibition of erythroid but not myeloid progenitor cells.     

Plastic-adherent progenitor cells in mobilized peripheral blood progenitor cell collections

The use of peripheral blood progenitor cells (PBPC) to reconstitute hematopoiesis after high-dose chemoradiotherapy is now commonplace in the treatment of malignancies. Attempts to characterize these cells have concentrated primarily on their phenotype and their content of clonogenic colony-forming cells (CFC). We have used a plastic-adherent delta (P delta) assay system to evaluate the quantity and quality of more primitive cells in addition to the conventional measurements of CFC and CD34-positive cells. The leukapheresis products from 20 patients mobilized using cyclophosphamide (Cy) and granulocyte colony- stimulating factor (G-CSF) were examined for progenitor cell content. The mean number of mononuclear cells (MNC), colony-forming units- granulocyte/macrophage (CFU-GM), and CD34-positive cells from two leukaphereses per patients were 7.9 x 10(8)/kg, 47.3 x 10(4)/kg, and 10.5 x 10(6)/kg, respectively. The mean number of P delta progenitors was 9.3 x 10(4)/kg. Limiting dilution analyses showed the frequency of P delta progenitors in PBPC to be between 1 and 5.3 per 10(5) MNC and that each P delta progenitor has the proliferative capability to generate an overall mean of 4.5 CFU-GM. Of the 20 patients, 16 underwent autografting with PBPC alone. Fifteen patients engrafted neutrophils and platelets within 16 days. One patient had delayed engraftment associated with inadequate etoposide clearance. Statistical analysis showed a strong correlation between numbers of CFU-GM and CD34 positivity. The numbers of plastic-adherent P delta progenitor cells did not correlate with CFU-GM or CD34-positive cells. We conclude that the plastic-adherent P delta progenitor cell assay is capable of measuring primitive hematopoietic cells and that it may be useful for the investigation of primitive progenitors in PBPC harvests.     

A novel protein-repellent dental composite containing 2-methacryloyloxyethyl phosphorylcholine

Secondary caries due to biofilm acids is a primary cause of dental composite restoration failure.To date,there have been no reports of dental composites that can repel protein adsorption and inhibit bacteria attachment.The objectives of this study were to develop a protein-repellent dental composite by incorporating 2-methacryloyloxyethyl phosphorylcholine(MPC) and to investigate for the first time the effects of MPC mass fraction on protein adsorption,bacteria attachment,biofilm growth,and mechanical properties.Composites were synthesized with 0(control),0.75%,1.5%,2.25%,3%,4.5%and 6%of MPC by mass.A commercial composite was also tested as a control.Mechanical properties were measured in three-point flexure.Protein adsorption onto the composite was determined by the microbicinchoninic acid method.A human saliva microcosm biofilm model was used.Early attachment at 4 h,biofilm at 2 days,live/dead staining and colony-forming units(CFUs) of biofilms grown on the composites were investigated.Composites with MPC of up to 3%had mechanical properties similar to those without MPC and those of the commercial control,whereas 4.5%and 6%MPC decreased the mechanical properties(P<0.05).Increasing MPC from 0 to 3%reduced the protein adsorption on composites(P<0.05).The composite with 3%MPC had protein adsorption that was 1/12 that of the control(P<0.05).Oral bacteria early attachment and biofilm growth were also greatly reduced on the composite with 3%MPC,compared to the control(P<0.05).In conclusion,incorporation of MPC into composites at 3%greatly reduced protein adsorption,bacteria attachment and biofilm CFUs,without compromising mechanical properties.Protein-repellent composites could help to repel bacteria attachment and plaque build-up to reduce secondary caries.The protein-repellent method might be applicable to other dental materials.