Membrane knobs are required for the microcirculatory obstruction induced by Plasmodium falciparum-infected erythrocytes.

We have studied the pathophysiology of the vascular obstruction induced by Plasmodium falciparum-parasitized erythrocytes with the use of an ex vivo microcirculatory preparation perfused with red cells infected with knobless and knobby clones of the FCR-3 strain. We find that parasitized erythrocyte membrane knobs are indispensable for the generation of the circulatory obstruction. Uninfected erythrocytes incubated in culture and erythrocytes infected with early or late forms of the knobless clones or the early forms of the knobby clone all failed to obstruct the microcirculation, although exhibiting various effects on bulk viscosity and peripheral resistance during flow. In contrast, late forms of the knobby clone produced significantly higher peripheral resistance during flow and significant obstruction as detected by changes in time of pressure flow recovery as well as by direct videorecorded microscopic observation. Optical and electron microscopy showed that the adherence of parasitized cells to the endothelium was limited to the venules and involved the knobs in junctions. In addition, we were able to follow the sequence of events during obstruction: initial red-cell adherence to the venular endothelium (sometimes only transitory) followed by progressive recruitment at the venule surface, finally leading to total obstruction that involved parasitized and nonparasitized erythrocytes. Sometimes, retrograde aggregation would extend the obstruction to the capillaries or even precapillary arterioles. These results show that knobs are necessary and sufficient to produce vascular obstruction and that other factors (spleen, immunological, etc.) can only have a modulating role. These results also exclude the possibility that the exclusive adherence to venules is the consequence of "plasma factors" found in the malaric patients.     

The effect of lengthening the gastrocnemius muscle in chronic therapy resistant plantar fasciitis

BackgroundThe aetiology of chronic therapy resistant plantar fasciitis (CTRPF) is multifactorial with more focus in recent times on the gastroc-soleus complex. This study evaluates the effect of lengthening the gastrocnemius muscle in CTRPF.MethodsAll patients with CRTPF complaints for at least one year underwent the same standard conservative treatment prior to surgery. 32 patients failed this treatment and underwent gastrocnemius recession. Silfverskiöld test, questionnaires and plantar pressure measurements were obtained at 5 visits.ResultsOne year follow up showed a significantly increase in dorsiflexion of the ankle (16 degrees), a decrease in VAS; 78 (SD: 19) to 20 (SD: 24) and significant improved functional scores. Plantar pressure measurements showed an increase of pressure under the medial proximal part of the midfoot and the 1 st metatarsal and a decrease under the hallux.ConclusionsA gastrocnemius recession results in a significant gain in dorsiflexion, altered loading of the foot and good clinical outcome in patients with CTRPF.Level of EvidenceLevel 2     

Inflamed fibronectin: an altered fibronectin enhances neutrophil adhesion

Recent investigations have emphasized the role of activated granulocytes in mediating vascular endothelial injury in the pathogenesis of shock lung. In vitro studies have indicated that tight adherence of the neutrophil to the endothelium is crucial for the development of cellular injury. Fibronectin is critical to cell-to- substratum and cell-to-cell interactions. Since fibronectin resides in plasma, on endothelial cell surfaces and is secreted into cell matrices, the adhesive properties of fibronectin must be modulated, lest universal cell agglomeration occur, yet be enhanced when cell attachment is appropriate. In these studies, treatment of fibronectin- coated surfaces with neutrophil release products increased the adhesion of activated neutrophils. Similarly, endothelial cells treated with neutrophil release products become a more adherent substrate for neutrophils. This enhanced adherence generated by treatment of fibronectin with neutrophil supernatants is inhibitable by heat and the lysosomal proteinase inhibitor, pepstatin-A. Neutrophil release products cause proteolytic fragmentation of fibronectin and enhanced fibronectin immunofluorescence on endothelial cells. In addition, neutrophils are more injurious to endothelial cells that have been pretreated with neutrophil release products. Neutrophils may enhance their own adherence to endothelial cells by altering fibronectin, and this altered, or "inflamed," fibronectin may serve as an amplifier of inflammation.     

Changes in glucose level affect rod function more than cone function in the isolated, perfused cat eye.

The glucose concentration (gl) in mammalian serum incorporates a normal range of variation of several millimoles. We studied the effects of such variations on light-evoked electrical signals in the in vitro arterially perfused cat eye, avoiding extraocular regulatory mechanisms that might confound data interpretation. Changes in gl from the nominal control value of 5 mmol/l were maintained for 5-40 min. Stimuli of near rod threshold intensity were presented in full dark adaptation, and stimuli of higher intensity were presented in the presence of a white background for cone responses. We recorded the dc-electroretinogram (ERG), the scotopic threshold response (STR), the optic nerve response (ONR), and the transretinal slow P-III and transepithelial retinal pigment epithelium c-wave from the subretinal space. The ocular standing potential changed by up to +/- 2 mV in parallel with an increase and decrease in gl, independent of the adaptation condition. Our results show that the rod-ERG, STR, and rod-driven optic nerve response (ONR) have a marked sensitivity to small changes in gl (+/- 1 to 3 mmol/l). The field potentials increased and decreased in parallel with changes in gl. The cone ERG and cone ONR, in contrast, failed to respond consistently to increases in gl and revealed decreases in amplitudes only with an extreme decrease in gl. Decrease in gl, down to 2 mmol/l and less, is known to induce drastic behavioral and electrophysiologic phenomena in the central nervous system. Our results imply that the "normal" glucose level, at least in the cat, could be marginal for rod-mediated retinal function. The results also suggest a marked difference in metabolic mechanisms for cone versus rod photoreceptors.     

Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse

The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in ApcMin mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male ApcMin mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.      

菊叶三七生物碱成分的研究

从菊科蒂叶三七植物中分离出六个生物碱,对其中四个进行了鉴定。光谱数据证明:生物碱Ⅰ和Ⅱ分别为已知的千里光碱(senecionine,Ⅰ)和千里光菲灵碱(seneciphylline,Ⅱ),生物碱Ⅲ和Ⅳ为新成分,分别命名为菊三七碱甲(sineciphyllinine,Ⅲ)和菊三七碱乙[(E)-seneciphylline,Ⅳ]。     

Color Conversion Light-Emitting Diodes Based on Carbon Dots: A Review

This paper reviews the state-of-the-art technologies, characterizations, materials (precursors and encapsulants), and challenges concerning multicolor and white light-emitting diodes (LEDs) based on carbon dots (CDs) as color converters. Herein, CDs are exploited to achieve emission in LEDs at wavelengths longer than the pump wavelength. White LEDs are typically obtained by pumping broad band visible-emitting CDs by an UV LED, or yellow–green-emitting CDs by a blue LED. The most important methods used to produce CDs, top-down and bottom-up, are described in detail, together with the process that allows one to embed the synthetized CDs on the surface of the pumping LEDs. Experimental results show that CDs are very promising ecofriendly candidates with the potential to replace phosphors in traditional color conversion LEDs. The future for these devices is bright, but several goals must still be achieved to reach full maturity.     

Effect of Parasympathetic Stimulation on Brain Activity During Appraisal of Fearful Expressions

Autonomic nervous system activity is an important component of human emotion. Mental processes influence bodily physiology, which in turn feeds back to influence thoughts and feelings. Afferent cardiovascular signals from arterial baroreceptors in the carotid sinuses are processed within the brain and contribute to this two-way communication with the body. These carotid baroreceptors can be stimulated non-invasively by externally applying focal negative pressure bilaterally to the neck. In an experiment combining functional neuroimaging (fMRI) with carotid stimulation in healthy participants, we tested the hypothesis that manipulating afferent cardiovascular signals alters the central processing of emotional information (fearful and neutral facial expressions). Carotid stimulation, compared with sham stimulation, broadly attenuated activity across cortical and brainstem regions. Modulation of emotional processing was apparent as a significant expression-by-stimulation interaction within left amygdala, where responses during appraisal of fearful faces were selectively reduced by carotid stimulation. Moreover, activity reductions within insula, amygdala, and hippocampus correlated with the degree of stimulation-evoked change in the explicit emotional ratings of fearful faces. Across participants, individual differences in autonomic state (heart rate variability, a proxy measure of autonomic balance toward parasympathetic activity) predicted the extent to which carotid stimulation influenced neural (amygdala) responses during appraisal and subjective rating of fearful faces. Together our results provide mechanistic insight into the visceral component of emotion by identifying the neural substrates mediating cardiovascular influences on the processing of fear signals, potentially implicating central baroreflex mechanisms for anxiolytic treatment targets.