Angiogenic factors stimulate mast-cell migration

Mast cells accumulate at sites of angiogenesis. The factor(s) that control mast-cell recruitment at these sites have yet to be defined. We sought to determine if angiogenic factors result in mast-cell chemotaxis. In this study, we observed that platelet-derived growth factor-AB (PDGF-AB), vascular endothelial cell growth factor (VEGF), and basic fibroblast growth factor (bFGF) each cause directed migration of murine mast cells at picomolar concentrations, with a typical bell- shaped dose-response curve. Another potent angiogenic factor, platelet- derived endothelial cell growth factor (PD-ECGF), appears to promote chemokinesis of mast cells, whereas tumor necrosis factor-alpha, a weak angiogenic factor, is less robust but still functions as a mast cell chemotactic factor. Epidermal growth factor (EGF), a growth factor with minimal angiogenic properties, was ineffective as a mast cell chemotactic factor. A checkerboard analysis confirmed the directional chemotactic response of PDGF-AB, VEGF, and bFGF, while indicating the chemokinetic response induced by PD-ECGF. Cross-desensitization of growth-factor-induced directed migration was observed between PDGF-AB and bFGF, and also between PDGF-AB and PD-ECGF. Tyrosine kinase- inhibitor genistein effectively dampened the chemotactic responses, whereas pertussis toxin had no effect. In summary, our findings suggest that factors known to act on endothelial cells and stimulate neovascularization may simultaneously serve to recruit mast cells to these sites. The local accumulation of mast cells is believed to facilitate new vessel formation through complex cell:cell interactions.     

Magnetic and spectroscopic properties of Ni–Zn–Al ferrite spinel: from the nanoscale to microscale

This article presents the annealing effect on the structural, elastic, thermodynamic, optical, magnetic, and electric properties of Ni_0.6Zn_0.4Fe_1.5Al_0.5O₄ (NZFAO) nanoparticles (NPs). The samples were successfully synthesized by the sol–gel method followed by annealing of the as-synthesized at 600, 800, 900, 1050, and 1200 °C. This approach yielded the formation of a highly crystalline structure with crystallite size ranging from 17 nm to 40 nm. X-ray diffraction (XRD), scanning electron microscopy (SEM) techniques, as well as energy disperse spectroscopy (EDS), Fourier transform infrared (FTIR) and Raman spectroscopy, were used in order to determine the structural and morphological properties of the prepared samples. Rietveld XRD refinement reveals that Ni–Zn–Al ferrite nanoparticles crystallize in inverse cubic (Fd$\bar{3}$m) spinel structure. Using FTIR spectra, the elastic and thermodynamic properties were estimated. It was observed that the particle size had a pronounced effect on elastic and thermodynamic properties. Magnetic measurements were performed up to 700 K. The prepared ferrite samples present the highest Curie temperature, which decreases with increasing particle size and which is consistent with finite-size scaling. The thickness of the surface shell of about 1 nm was estimated from size-dependent magnetization measurements using the core–shell model. Besides, spin resonance, magnetostriction, temperature coefficient of resistance (TCR), and electrical resistivity properties have been scientifically studied and appear to be different according to their size. The optical properties of synthesized NZFAO nanoparticles were investigated, and the differences caused by the particle sizes are discussed on the basis of the phonon confinement effect. This effect was also inspected by the Raman analysis. Tuning of the physical properties suggests that the Ni–Zn–Al ferrite samples may be promising for multifunctional diverse applications.

This article presents the annealing effect on the structural, elastic, thermodynamic, optical, magnetic, and electric properties of Ni_0.6Zn_0.4Fe_1.5Al_0.5O₄ (NZFAO) nanoparticles (NPs).     

Structural,optical and dielectric properties of Cu1.5Mn1.5O4 spinel nanoparticles

In this study, a Cu_1.5Mn_1.5O₄ spinel was successfully synthesized by a sol–gel method at 500 °C for 5 h and characterized by different techniques. X-ray diffraction (XRD), Fourier transformation infrared (FTIR) spectroscopy and Raman spectroscopic analyses confirmed the formation of a spinel cubic structure with the Fd$\bar{3}$m space group. The SEM proves that the grain size of our compound is of the order of 48 nm. Crystallite sizes determined from three estimates are closer to the grain size obtained from the SEM, indicating the single domain nature of the sample. The optical properties of UV-visible spectroscopy for our sample showed that the gap value is equal to 3.82 eV, making our compound a good candidate for optoelectronic applications. For electrical properties, impedance spectroscopy was performed at a frequency range of 40 ≤ frequency ≤ 10⁶ Hz. This suggested hoping conduction due to three theoretical models. The latter can be attributed to the correlated barrier hopping (CBH) model in region I, overlapping large polaron tunneling (OLPT) in region II and non-overlapping small polaron tunneling (NSPT) mechanism in region III. One dielectric relaxation is detected from the dielectric impedance and modulus, attributed to grain contributions. This behavior was confirmed by both Nyquist and Argand''s plots of dielectric impedance at different measuring temperatures.

In this study, a Cu_1.5Mn_1.5O₄ spinel was successfully synthesized by a sol–gel method at 500 °C for 5 h and characterized by different techniques.     

Fluorescence in situ hybridization mapping of translocations and deletions involving the short arm of human chromosome 12 in malignant hematologic diseases

Translocations and deletions of the short arm of chromosome 12 [t(12p) and del(12p)] are common recurring abnormalities in a broad spectrum of hematologic malignant diseases. We studied 20 patients and one cell line whose cells contained 12p13 translocations and/or 12p deletions using fluorescence in situ hybridization (FISH) with phage, plasmid, and cosmid probes that we previously mapped and ordered on 12p12-13. FISH analysis showed that the 12p13 translocation breakpoints were clustered between two cosmids, D12S133 and D12S142, in 11 of 12 patients and in one cell line. FISH analysis of 11 patients with deletions demonstrated that the deletions were interstitial rather than terminal and that the distal part of 12p12, including the GDI-D4 gene and D12S54 marker, was deleted in all 11 patients. Moreover, FISH analysis showed that cells from 3 of these patients contained both a del(12p) and a 12p13 translocation and that the affected regions of these rearrangements appeared to overlap. We identified three yeast artificial chromosome (YAC) clones that span all the 12p13 translocation breakpoints mapped between D12S133 and D12S142. They have inserts of human DNA between 1.39 and 1.67 Mb. Because the region between D12S133 and D12S142 also represents the telomeric border of the smallest commonly deleted region of 12p, we also studied patients with a del(12p) using these YACs. The smallest YAC, 964c10, was deleted in 8 of 9 patients studied. In the other patient, the YAC labeled the del(12p) chromosome more weakly than the normal chromosome 12, suggesting that a part of the YAC was deleted. Thus, most 12p13 translocation breakpoints were clustered within the sequences contained in the 1.39 Mb YAC and this YAC appears to include the telomeric border of the smallest commonly deleted region. Whether the same gene is involved in both the translocations and deletions is presently unknown.     

Diabetes Patients' Experiences With the Implementation of Insulin Therapy and Their Perceptions of Computer-Assisted Self-Management Systems for Insulin Therapy

Background

Computer-assisted decision support is an emerging modality to assist patients with type 2 diabetes mellitus (T2DM) in insulin self-titration (ie, self-adjusting insulin dose according to daily blood glucose levels). Computer-assisted insulin self-titration systems mainly focus on helping patients overcome barriers related to the cognitive components of insulin titration. Yet other (eg, psychological or physical) barriers could still impede effective use of such systems.

Objective

Our primary aim was to identify experiences with and barriers to self-monitoring of blood glucose, insulin injection, and insulin titration among patients with T2DM. Our research team developed a computer-assisted insulin self-titration system, called PANDIT. The secondary aim of this study was to evaluate patients’ perceptions of computer-assisted insulin self-titration. We included patients who used PANDIT in a 4-week pilot study as well as patients who had never used such a system.

Methods

In-depth, semi-structured interviews were conducted individually with patients on insulin therapy who were randomly recruited from a university hospital and surrounding general practices in the Netherlands. The interviews were transcribed verbatim and analyzed qualitatively. To classify the textual remarks, we created a codebook during the analysis, in a bottom-up and iterative fashion. To support examination of the final coded data, we used three theories from the field of health psychology and the integrated model of user satisfaction and technology acceptance by Wixom and Todd.

Results

When starting insulin therapy, some patients feared a lifelong commitment to insulin therapy and disease progression. Also, many barriers arose when implementing insulin therapy (eg, some patients were embarrassed to inject insulin in public). Furthermore, patients had difficulties increasing the insulin dose because they fear hypoglycemia, they associate higher insulin doses with disease progression, and some were ignorant of treatment targets. Patients who never used a computer-assisted insulin self-titration system felt they had enough knowledge to know when their insulin should be adjusted, but still believed that the system advice would be useful to confirm their reasoning. Furthermore, the time and effort saved with automated insulin advice was considered an advantage. Patients who had used PANDIT found the system useful if their glycemic regulation improved. Nevertheless, for some patients, the absence of personal contact with their caregiver was a drawback. While guidelines state that adjustment of basal insulin dose based on fasting plasma glucose values is sufficient, both patients who had and those who had not used PANDIT felt that such a system should take more patient data into consideration, such as lifestyle and diet factors.

Conclusions

Patients encounter multiple obstacles when implementing insulin therapy. Computer-assisted insulin self-titration can increase patient awareness of treatment targets and increase their confidence in self-adjusting the insulin dose. Nevertheless, some barriers may still exist when using computer-assisted titration systems and these systems could also introduce new barriers.     

Study of physical properties of a ferrimagnetic spinel Cu1.5Mn1.5O4: spin dynamics,magnetocaloric effect and critical behavior

The present work reports a detailed study of the spin dynamics, magnetocaloric effect and critical behaviour near the magnetic phase transition temperature, of a ferrimagnetic spinel Cu_1.5Mn_1.5O₄. The dynamic magnetic properties investigated using frequency-dependent ac magnetic susceptibility fitted using different phenomenological models such as Neel–Arrhenius, Vogel–Fulcher and power law, strongly indicate the presence of a cluster-glass-like behavior of Cu_1.5Mn_1.5O₄ at 40 K. The magnetization data have revealed that our compound displays an occurrence of second-order paramagnetic (PM) to ferrimagnetic (FIM) phase transition at the Curie temperature T_C = 80 K as the temperature decrease. In addition, the magnetic entropy change (ΔS_M) was calculated using two different methods: Maxwell relations and Landau theory. An acceptable agreement was found between both sets of data, which proves the importance of both electron interaction and magnetoelastic coupling in the magnetocaloric effect (MCE) properties of Cu_1.5Mn_1.5O₄. The relative cooling power (RCP) reaches 180.13 (J kg⁻¹) for an applied field at 5 T, making our compound an effective candidate for magnetic refrigeration applications. The critical exponents β, γ and δ as well as transition temperature T_C were extracted from various techniques indicating that the magnetic interaction in our sample follows the 3D-Ising model. The validity of the critical exponents is confirmed by applying the Windom scaling hypothesis.

The present work reports a detailed study of the spin dynamics, magnetocaloric effect and critical behaviour near the magnetic phase transition temperature, of a ferrimagnetic spinel Cu_1.5Mn_1.5O₄.     

Comparison of enoxaparin and unfractionated heparin in endovascular interventions for the treatment of peripheral arterial occlusive disease: a randomized controlled trial

Summary. Background: Although unfractionated heparin (UFH) is an effective antithrombotic agent in endovascular interventions for the treatment of peripheral occlusive arterial disease (PAOD), it produces a highly variable anticoagulant response. Intravenous (i.v.) enoxaparin might be an effective and safe alternative. Patients and methods: In a prospective, open‐label, randomized, single‐center trial, 210 patients with PAOD (Fontaine stage IIb to IV) were randomly assigned in a 1 (UFH): 2 (enoxaparin) fashion to receive an i.v. bolus of 60 units UFH per kg body weight or 0.5 mg enoxaparin per kg body weight, respectively, before endovascular intervention. The primary composite endpoint assessed the clinical performance of enoxaparin by comparing the peri‐interventional rate of thromboembolia/occlusion (efficacy) of endovascularly reconstructed areas, of bleeding according to the Global Utilization of Streptokinase and t‐PA for Occluded Coronary Arteries (GUSTO) criteria (safety) and of any necessary re‐intervention for any percutaneous transluminal angioplasty (PTA)‐related bleeding. The secondary endpoint evaluated anti‐factor (F)Xa levels during intervention. Results: The primary composite endpoint showed a better performance of enoxaparin (10.5% vs. 2.5% absolute difference – 8.0%; P < 0.05). The concomitant use of acetylsalicylic acid (ASA) significantly (P < 0.05) increased the risk of a complication in the UFH group, but not in the enoxaparin group. Within 15 min, anti‐Xa levels were reached by 63.7% of patients treated with enoxaparin and only by 39.1% with UFH. Conclusion: Enoxaparin has a better performance than UFH in endovascular interventions for the treatment of PAOD. In patients with concomitant use of ASA, the risk of complications with UFH increases significantly compared with enoxaparin.     

糖尿病大鼠骨代谢变化与立普妥、胰岛素的干预效应

目的:近年细胞培养实验发现他汀类药物可以促进骨形成,采用动物实验观察胰岛素和他汀类药物立普妥对糖尿病大鼠骨代谢的影响,为糖尿病伴骨质疏松的治疗提供实验依据。方法:实验于2005-08/2006-01在大连医科大学病理教研室完成。①实验分组:SD雄性大鼠55只,随机选择10只为空白对照组,余45只经鼠尾静脉注射链尿佐菌素造成糖尿病大鼠模型。其中40只符合造模标准,随机分为糖尿病未治疗组、胰岛素治疗组、立普妥治疗组及胰岛素 立普妥治疗组,每组10只。②实验方法:所有大鼠皆给予相同普通饮食。胰岛素治疗组及胰岛素 立普妥治疗组于实验第4天接受中效胰岛素治疗,6～8U/d分两次颈背部皮下注射。胰岛素剂量按每只鼠每周血糖进行调整。立普妥治疗组及胰岛素 立普妥治疗组于实验第4天给予立普妥1.25mg/kg灌胃。糖尿病未治疗组和空白对照组给予等量生理盐水灌胃。③实验评估:9周末用乙醚麻醉,每组取4只大鼠去眼球取血之后处死。14周末应用同样方法处死剩余大鼠。均取腰椎骨,常规脱钙石蜡包埋,行苏木精-伊红染色。骨组织形态计量学测量平均骨小梁厚度和平均骨小梁间距或弥散度。血中Ⅰ型胶原氨基端肽测定采用竞争性放射免疫检测方法(碘标记)。结果:实验期间大鼠死亡5只,其中糖尿病未治疗组1只于第3周死亡,胰岛素组2只于第6周死亡,胰岛素 立普妥治疗组2只于第7周死亡。①骨组织病理形态学变化:9周末立普妥治疗组、胰岛素 立普妥治疗组及糖尿病未治疗组光镜下见骨质疏松表现。14周末立普妥治疗组及胰岛素治疗组骨组织微观结构恢复至空白对照组水平。②平均骨小梁厚度:9周末:糖尿病未治疗组、胰岛素治疗组、立普妥治疗组及胰岛素 立普妥治疗组均明显低于空白对照组(P<0.01)。14周末:糖尿病未治疗组及胰岛素 立普妥治疗组均明显低于空白对照组(P<0.05)。③平均骨小梁间距或弥散度:9周末:糖尿病未治疗组及胰岛素 立普妥治疗组均明显高于空白对照组(P<0.05)。14周末:糖尿病未治疗组及胰岛素 立普妥治疗组均明显高于空白对照组(P<0.05)。④Ⅰ型胶原氨基端肽水平:9周末:立普妥治疗组和胰岛素 立普妥治疗组均明显高于空白对照组(P<0.01)。14周末:胰岛素治疗组、立普妥治疗组和胰岛素 立普妥治疗组均明显高于空白对照组(P<0.01)。结论:①糖尿病大鼠造模9周出现明显的骨质疏松。②糖尿病大鼠骨质变化表现为骨吸收超过骨形成作用,主要以骨吸收增强为主。③立普妥及胰岛素可以促进糖尿病大鼠骨质的形成,抑制糖尿病大鼠骨质疏松的发生发展。