Regional changes of brain serotonin and its metabolite 5-hydroxyindolacetic Acid and development of immunosuppression in submissive mice

The production of submissive behavior in C57BL/6J mice during 10 or 20 days of social confrontations resulted in increases in serotonin (5-HT) content in the amygdala, hippocampus, nucleus caudatus, Al1, A10, A9, and hypothalamus. The level of 5-hydroxyindolacetic acid (5-HIAA) was higher in most structures after 20 daily encounters compared to animals tested for 10 days. The ratio 5-HIAA/5-HT was increased in the nucleus raphe, accumbens, A9, and hypothalamus in mice displaying submission during 10 and 20 confrontations. The experience of defeats during 10 days accompanied with 5-HT system activation in a number of brain structures (nucleus raphe, accumbens, and A9) produced immunosuppression. With increasing number of confrontations the ratio 5-HIAA/5-HT was decreased in the same structures and a tendency to the immune response elevation appeared.     

Ultrasound imaging of the infraorbital foramen and simulation of the ultrasound-guided infraorbital nerve block using a skull model

Purpose

Infraorbital nerve block is used for intraoperative and postoperative analgesia in nasal and oral surgery procedures, as well as in the chronic pain settings. Ultrasound guidance has not been described in the literature. The aim of the study was to assess the quality of ultrasound imaging of the infraorbital foramen and develop an “in-plane” technique of the block using a skull model.

Methods

The infraorbital foramina were assessed on five skull models immersed in the water bath. Ultrasound-guided simulation of an in-plane infraorbital nerve block was then performed. Slightly curved needle was placed close to the foramina and its visibility was recorded. Success rate and time to locate infraorbital foramina, success rate and time to insert the needle close to the foramina under ultrasound and correlation between the ultrasound and caliper measurements were evaluated and recorded. Data for the left and right foramen were compared.

Results

The infraorbital foramina were successfully located using ultrasound in all 20 cases. Simulation of infraorbital nerve block was also successful in all measurements. The time difference between locating or simulating blockade of the left and right infraorbital foramina was not statistically significant. Correlation between ultrasound measurement and direct measurement using a caliper was satisfactory for the distances between the inferior orbital rim and the inferior margin of the infraorbital foramen but poor for the distances between the lower rim of the orbit and the superior margin of the foramen.

Conclusions

This experimental study suggests that the infraorbital foramen is easily located using ultrasound and an “in-plane” ultrasound-guided technique for infraorbital nerve blockade is feasible on the model.     

New Chemically Resistant Coating Systems with Progressive Incorporation of Hazardous Waste in Polyurethane and Epoxy Matrices

New types of highly chemically resistant coating systems, primarily intended for concrete and metal substrates, were designed and experimentally verified in the paper. Secondary raw materials in optimal amounts, including solidified hazardous waste (e.g., end product and cement bypass dust), were used as microfillers. The polymer coating systems, containing pre-treated hazardous waste (HW), showed high abrasion resistance and excellent adhesion to metal and concrete surfaces. Based on polyurethane and epoxy resins, the coatings can be used in environments where aggressive chemical media act, such as sewers and the chemical industry. The developed polymeric coating systems showed even better properties than the compared reference coating systems. The chemical resistance of the three-layer coating systems was evaluated both visually and based on changes in mechanical properties, such as hardness and adhesion. The microstructure of the coating systems was also monitored using a digital optical microscope and a scanning electron microscope with energy dispersive X-ray analysis (SEM-EDX) after chemical stress. It was observed that the particles of HW were fully incorporated into the polymer matrix of the coating systems.     

Crack-Resistant Cements under Drying: Results from Ring Shrinkage Tests and Multi-Physical Modeling

Cementitious materials exhibit shrinkage strain on drying, leading easily to crack formation when internally or externally restrained. It is known that cements with a slow strength gain show higher crack resistance under external drying. The ring shrinkage test can be considered an accelerated method for cracking tendency due to existing historical correlations between ring cracking time and long-term surface concrete cracking. The experimental campaign used ring shrinkage tests on 25 mortars, covering 10 commercial cements and 15 cements produced on demand, covering Portland cements and blended cements up to a 30% slag substitution. The results show that the restrained ring cracking time generally increases with lower Blaine fineness and higher slag substitution in 6 to over 207 days’ span. Upper limits for crack-resistant cements were proposed for 2-day compressive strength and Blaine fineness, in the case of Portland cements: 27.7 MPa and 290 m²/kg, respectively. A hygro-mechanical model successfully replicated strain evolution with crack formation and brittle failure. Only two out of ten commercial cements were classified as crack-resistant, while the ratio increased to 10 out of 15 cements which were produced on demand.     

Clinical and laboratory prognostic factors in patients with metastatic renal cell carcinoma treated with sunitinib and sorafenib after progression on cytokines

ObjectivesThe aim of this retrospective study was to analyze prognostic factors in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors (TKIs) sunitinib or sorafenib after progression on cytokine therapy.Materials and methodsA national database of patients treated with targeted agents was used as the data source. A total of 319 patients treated with sunitinib (n = 181) or sorafenib (n = 138) after progression on cytokine therapy were analyzed.ResultsPrognostic factors significantly associated with poor overall survival in a multivariable Cox model included the time from diagnosis to the start of treatment with TKIs<1 year, increased neutrophil counts, increased lactate dehydrogenase, and Eastern Oncology Cooperative Group performance status 2 or higher. The parameters showing statistically significant association with progression-free survival included time from diagnosis to the beginning of treatment with TKI<1 year, increased lactate dehydrogenase, and Eastern Oncology Cooperative Group performance status 2 or higher. We have also validated the International Metastatic Renal Cell Carcinoma Database Consortium prognostic model in our cohort of patients.ConclusionWe demonstrate that the International Database Consortium prognostic model performs well for European patients treated with TKIs, including sunitinib or sorafenib, after progression on cytokines and suggest that a reduction from original 6 down to 4 parameters is possible.     

Spontaneous Openings of NMDA Receptor Channels in Cultured Rat Hippocampal Neurons

Spontaneous and N-methyl-D-aspartate (NMDA)-evoked single-channel currents were studied in outside-out patches isolated from cultured rat hippocampal neurons. Both spontaneous and NMDA-evoked single-channel currents reversed at potentials close to 0 mV and exhibited multiple amplitude levels of similar amplitude. Both spontaneous and NMDA-evoked single-channel currents were inhibited by Mg²⁺ in a voltage-dependent manner and by 7-chlorokynurenic acid. The activity of spontaneous single-channel currents was reduced by the competitive NMDA receptor antagonists, but by one to three orders of magnitude less than expected assuming that the spontaneous activity is due to an ambient NMDA receptor agonist present in the extracellular solution. Our results suggest that, similar to other ligand-gated ion channels, NMDA receptor channels have a dual mode of activation - spontaneous and agonist induced.     

Cardiac CD68+ and stabilin-1+ macrophages in wound healing following myocardial infarction: From experiment to clinic

Myocardial infarction (MI) remains the leading cause of mortality and morbidity throughout the world. Macrophages are key innate immune cells that play a significant role in transition from the inflammatory to the regenerative phase during wound healing following MI. The scavenger receptor stabilin-1 is one of the most interesting macrophage biomarkers. This receptor contributes to wound healing, angiogenesis, and tissue remodeling. We suggested a research protocol using macrophage biomarkers to study the cellular basis of cardiac remodeling and healing in patients with acute MI. The purpose of the research was to translate experimental knowledge regarding macrophage subsets and their biomarkers in post-infarction myocardial regeneration into results observed in clinical settings. The study included 41 patients with fatal MI type 1. All patients were divided into four groups according to the timeline of MI histopathology. In addition to routine histopathological analysis, macrophage infiltration was assessed by immunohistochemistry. We used CD68 as a marker for the cells of the macrophage lineage and stabilin-1 as an M2-like macrophage biomarker. The number of CD68+ and stabilin-1+ macrophages in the infarct area increased and peaked in the regenerative phase and did not decrease in the late stage of MI. In the peri-infarct area, the number of CD68+ macrophages increased in the inflammatory phase, peaked during the reparative phase, and did not decrease in the late phase, while the number of stabilin-1+ macrophages increased in the regenerative phase and remained unchanged. Additionally, in the reparative phase, we observed increase in the number of CD68+ and stabilin-1+ macrophages in the non-infarct area. The research protocol suggested allowed us to translate experimental knowledge regarding macrophage subsets and their biomarkers in post-infarction myocardial regeneration into clinical data. Taken together, these results demonstrated biphasic cardiac macrophage response following acute MI somewhat similar to that in a murine model. The increase in stabilin-1+ macrophage infiltration noticed in the myocardium during the regenerative phase and the strong positive correlation between the number of these cells and timeline of MI histopathology enabled us to propose stabilin-1 as a diagnostic macrophage biomarker in myocardium wound healing in patients with acute MI.     

Bone mineral imaged in vivo by 31P solid state MRI of human wrists

Purpose:

To implement solid state ³¹P MRI (³¹P SMRI) in a clinical scanner to visualize bone mineral.

Materials and Methods:

Wrists of seven healthy volunteers were scanned. A quadrature wrist ³¹P transmit/receive coil provided strong B₁ and good signal‐to‐noise ratio (SNR). A ¹H‐³¹P frequency converter was constructed to enable detection of the ³¹P signal by means of the ¹H channel. Data points lost in the receiver dead time were recovered by a second acquisition with longer dwell time and lower gradient strength.

Results:

Three‐dimensional ³¹P images, showing only bone mineral of the wrist, were obtained with a clinical 3 Tesla (T) scanner. In the best overall case an image with isotropic resolution of ～5.1 mm and SNR of 30 was obtained in 37 min. ³¹P NMR properties (resonance line width 2 kHz and T₁ 17–19 s) of in vivo human bone mineral were measured.

Conclusion:

In vivo ³¹P SMRI visualization of human wrist bone mineral with a clinical MR scanner is feasible with suitable modifications to circumvent the scanners' limitations in reception of short‐T₂ signals. Frequency conversion methodology is useful for implementing ³¹P SMRI measurements on scanners which do not have multinuclear capability or for which the multinuclear receiver dead time is excessive. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.