Evaluation of laser-speckle contrast image analysis techniques in the cortical microcirculation of piglets

A new laser speckle-contrast analysis (LASCA) technique based on multi-exposure imaging was employed to simultaneously study pial arteriolar responses with cerebrocortical perfusion changes to various vasodilator (5-10% CO(2) ventilation, bradykinin (1-10 μM), N-methyl-D-aspartate (100 μM)) vasoconstrictor (10-100 μM noradrenaline, 1M KCl), or neutral (2.1% H(2) ventilation) stimuli as well as to asphyxia in the newborn piglet. Anesthetized, ventilated animals (n=20) were fitted with closed cranial windows. Multiple exposure laser-speckle image series (1-100 ms) were obtained using a near infrared diode laser (λ=808 nm). The autocorrelation decay time (τ) of speckle fluctuations was determined over pial arterioles and parenchymal areas to express 1/τ being proportional to blood flow velocity by two different LASCA techniques: our novel multi-exposure or a single exposure (2 and 20 ms) approach. 1/τ values yielded by different LASCA techniques were not significantly different at most points. LASCA easily detected both increases and decreases in cortical blood flow (CoBF). Cortical 1/τ changes to hypercapnia closely matched quantitative CoBF data determined previously, and were also in accordance with increases of pial arteriolar blood flow, calculated from arteriolar flow velocity and cross sectional area changes. In summary, LASCA emerges as an appealing method to simultaneously study microvascular reactivity and cortical perfusion changes in the piglet.     

The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.     

Interaction with plant transcription factors can mediate nuclear import of phytochrome B

Phytochromes (phy) are red/far-red-absorbing photoreceptors that regulate the adaption of plant growth and development to changes in ambient light conditions. The nuclear transport of the phytochromes upon light activation is regarded as a key step in phytochrome signaling. Although nuclear import of phyA is regulated by the transport facilitators far red elongated hypocotyl 1 (FHY1) and fhy1-like, an intrinsic nuclear localization signal was proposed to be involved in the nuclear accumulation of phyB. We recently showed that nuclear import of phytochromes can be analyzed in a cell-free system consisting of isolated nuclei of the unicellular green algae Acetabularia acetabulum. We now show that this system is also versatile to elucidate the mechanism of the nuclear transport of phyB. We tested the nuclear transport characteristics of full-length phyB as well as N- and C-terminal phyB fragments in vitro and showed that the nuclear import of phyB can be facilitated by phytochrome-interacting factor 3 (PIF3). In vivo measurements of phyB nuclear accumulation in the absence of PIF1, -3, -4, and -5 indicate that these PIFs are the major transport facilitators during the first hours of deetiolation. Under prolonged irradiations additional factors might be responsible for phyB nuclear transport in the plant.     

Comparison of aortic and carotid arterial stiffness parameters in patients with verified coronary artery disease

Background:

Arterial stiffness parameters are commonly used to determine the development of atherosclerotic disease. The independent predictive value of aortic stiffness has been demonstrated for coronary events.

Hypothesis:

The aim of our study was to compare regional and local arterial functional parameters measured by 2 different noninvasive methods in patients with verified coronary artery disease (CAD). We also compared and contrasted these stiffness parameters to the coronary SYNTAX score in patients who had undergone coronary angiography.

Methods:

In this study, 125 CAD patients were involved, and similar noninvasive measurements were performed on 125 healthy subjects. The regional velocity of the aortic pulse wave (PWVao) was measured by a novel oscillometric device, and the common carotid artery was studied by a Doppler echo‐tracking system to determine the local carotid pulse wave velocity (PWVcar). The augmentation index (AIx), which varies proportionately with the resistance of the small arteries, was recorded simultaneously.

Results:

In the CAD group, the PWVao and aortic augmentation index (Alxao) values increased significantly (10.1 ± 2.3 m/sec and 34.2% ± 14.6%) compared to the control group (9.6 ± 1.5 m/sec and 30.9% ± 12%; P < 0.05). We observed similar significant increases in the local stiffness parameters (PWVcar and carotid augmentation index [Alxcar]) in patients with verified CAD. Further, we found a strong correlation for PWV and AIx values that were measured with the Arteriograph and those obtained using the echo‐tracking method (r = 0.57, P < 0.001 for PWV; and r = 0.65, P < 0.001 for AIx values).

Conclusions:

Our results indicate that local and regional arterial stiffness parameters provide similar information on impaired arterial stiffening in patients with verified CAD. © 2011 Wiley Periodicals, Inc. This study was supported by the Hungarian National Research Foundation (OTKA) No.78480. The authors have no other funding, financial relationships, or conflicts of interest to disclose.     

Functional outcome after surgical treatment of orbital floor fractures

In the present article, the authors want to present the results of a retrospectively evaluated consecutive series of patients with surgically treated isolated orbital floor fractures (OFF; "blow-out fractures") concerning the functional outcome after OFF and give detailed recommendations based on the clinical and radiological findings. A series of 60 patients with isolated OFF over a 5-year period needing surgically repair at the same institution were evaluated. Patient data were analysed in terms of preoperative and postoperative clinical parameters and radiological findings. The analysed parameters were type of fracture, diplopia, gaze restriction, enophthalmos, materials used for repair, surgical approach and timing of the surgical intervention. Burst type fractures were more often found than punched-out fractures. The most frequently used surgical approach was a preseptal transconjunctival approach. An overall decrease of gaze restriction (93%), diplopia (89%) and enophthalmos (86%) was observed. According to the fracture size, we used Ethisorb patches in smaller fractures and resorbable or titanium meshes or autologous bone in larger fractures in most cases. Patients who underwent surgery more than 7 days after the trauma showed better results with regard to an improvement of diplopia and motility disturbances than patients who were treated immediately. In indicated cases, the surgical repair of OFF leads to very good results if the anatomical and functional properties of the orbit and its contents are respected. The applied strategy and means presented in our study proved of value and can therefore be recommended.