Current therapeutical strategies for allergic rhinitis

Introduction: Allergic rhinitis is a common condition with increasing prevalence and is associated with several comorbid disorders such as bronchial asthma and atopic dermatitis. If allergen avoidance is not possible, allergen-specific immunotherapy is the only causal treatment option.

Areas covered: This review focuses on current treatments and the future outlook for allergic rhinitis. Pharmacotherapy includes mast cell stabilizers, antihistamines, glucocorticosteroids (GCSs), leukotriene receptor antagonists, and nasal decongestants. Nasal GCSs are currently regarded as the most effective treatment and are considered first-line therapy together with non-sedating antihistamines. The new formulation MP29-02 combines the nasal GCS fluticasone propionate with azelastine in one single spray and has achieved greater improvements than those under monotherapy with modern GCSs or antihistamines. Furthermore, this review discusses allergen immunotherapy alone and in combination with modern monoclonal antibodies.

Expert opinion: Despite the variety of medications for allergic rhinitis, ranging from general symptomatic agents like GCSs or decongestants, to more specific ones like histamine receptor or leukotriene blockers, to causal therapy like immunotherapy, many patients still experience treatment failures or unsatisfactory results. The ultimate goal may be to endotype every downstream pathway separately in order to offer patients individualized, targeted therapy with specific antibodies against the respective pathway.     

Motion‐compensated b‐tensor encoding for in vivo cardiac diffusion‐weighted imaging

Motion is a major confound in diffusion‐weighted imaging (DWI) in the body, and it is a common cause of image artefacts. The effects are particularly severe in cardiac applications, due to the nonrigid cyclical deformation of the myocardium. Spin echo‐based DWI commonly employs gradient moment‐nulling techniques to desensitise the acquisition to velocity and acceleration, ie, nulling gradient moments up to the 2nd order (M2‐nulled). However, current M2‐nulled DWI scans are limited to encode diffusion along a single direction at a time. We propose a method for designing b‐tensors of arbitrary shapes, including planar, spherical, prolate and oblate tensors, while nulling gradient moments up to the 2nd order and beyond. The design strategy comprises initialising the diffusion encoding gradients in two encoding blocks about the refocusing pulse, followed by appropriate scaling and rotation, which further enables nulling undesired effects of concomitant gradients. Proof‐of‐concept assessment of in vivo mean diffusivity (MD) was performed using linear and spherical tensor encoding (LTE and STE, respectively) in the hearts of five healthy volunteers. The results of the M2‐nulled STE showed that (a) the sequence was robust to cardiac motion, and (b) MD was higher than that acquired using standard M2‐nulled LTE, where diffusion‐weighting was applied in three orthogonal directions, which may be attributed to the presence of restricted diffusion and microscopic diffusion anisotropy. Provided adequate signal‐to‐noise ratio, STE could significantly shorten estimation of MD compared with the conventional LTE approach. Importantly, our theoretical analysis and the proposed gradient waveform design may be useful in microstructure imaging beyond diffusion tensor imaging where the effects of motion must be suppressed.     

Protein kinase Cδ mediates trimethyltin-induced neurotoxicity in mice in vivo via inhibition of glutathione defense mechanism

We investigated whether protein kinase C (PKC) is involved in trimethyltin (TMT)-induced neurotoxicity. TMT treatment (2.8 mg/kg, i.p.) significantly increased PKCδ expression out of PKC isozymes (i.e., α, βI, βII, δ, and ?) in the hippocampus of wild-type (WT) mice. Consistently, treatment with TMT resulted in significant increases in cleaved PKCδ expression. Genetic or pharmacological inhibition (PKCδ knockout or rottlerin) was less susceptible to TMT-induced seizures than WT mice. TMT treatment increased glutathione oxidation, lipid peroxidation, protein oxidation, and levels of reactive oxygen species. These effects were more pronounced in the WT mice than in PKCδ knockout mice. In addition, the ability of TMT to induce nuclear translocation of Nrf2, Nrf2 DNA-binding activity, and upregulation of γ-glutamylcysteine ligase was significantly increased in the PKCδ knockout mice and rottlerin (10 or 20 mg/kg, p.o. × 6)-treated WT mice. Furthermore, neuronal degeneration (as shown by nuclear chromatin clumping and TUNEL staining) in WT mice was most pronounced 2 days after TMT. At the same time, TMT-induced inhibition of phosphoinositol 3-kinase (PI3K)/Akt signaling was evident, thereby decreasing phospho-Bad, expression of Bcl-xL and Bcl-2, and the interaction between phospho-Bad and 14-3-3 protein, and increasing Bax expression and caspase-3 cleavage were observed. Rottlerin or PKCδ knockout significantly protected these changes in anti- and pro-apoptotic factors. Importantly, treatment of the PI3K inhibitor LY294002 (0.8 or 1.6 µg, i.c.v.) 4 h before TMT counteracted protective effects (i.e., Nrf-2-dependent glutathione induction and pro-survival phenomenon) of rottlerin. Therefore, our results suggest that down-regulation of PKCδ and up-regulations of Nrf2-dependent glutathione defense mechanism and PI3K/Akt signaling are critical for attenuating TMT neurotoxicity.     

Counterfactual (‘if only’) thinking in women with chronic widespread pain

The study explored the counterfactual thinking that women with chronic and widespread pain showed in response to what they themselves considered to be particularly stressful situations. Counterfactual thinking in 125 women sick‐listed due to chronic and widespread pain was investigated in terms of structure, function and control focus. The women were asked, for each of three types of problems that they indicated in a questionnaire to affect them most strongly, to describe a typical occurrence of it and to complete a counterfactual sentence in connection with it of the type ‘If only . . .’. The majority of counterfactuals pertained to predominantly somatic problems (e.g. musculo‐skeletal problems, pain and fatigue) classified as being affective rather than preparative and self‐focused rather than external, whereas in counterfactuals relating to predominantly psychological/psychosocial problems a preparative function and an external focus were more prominent. The numbers of problems listed and the numbers of situations responded to counterfactually were positively correlated. The counterfactuals, although often related to somatic problems, generally concerned psychological or psychosocial matters such as finances and paid or unpaid work. A contextual approach to elucidating counterfactual thinking based on subjects' own experiences is seen as providing valuable insight into what bothers them most. Copyright © 2006 John Wiley & Sons, Ltd.     

Clinical indications and perspectives for intraoperative cone-beam computed tomography in oral and maxillofacial surgery.

OBJECTIVES: Intraoperative cone-beam computerized tomography (CBCT) imaging has been introduced in oral and maxillofacial surgery. Using midfacial fractures as the pioneer model, this study describes the spectrum of further promising clinical indications for intraoperative CBCT and a clinical combination with intraoperative navigation. STUDY DESIGN: One hundred seventy-nine patients admitted for surgical treatment of the facial skeleton were included in the study. Intraoperatively, 3-dimensional images were generated with the mobile CBCT scanner Arcadis Orbic 3D, obtained from Siemens Medical Solutions, in a variety of indications. RESULTS: The acquisition of the data sets was uncomplicated, and image quality was sufficient to assess the postoperative result in all cases. In the example of a facial gunshot injury, a navigation system for intraoperative localization of the metal foreign bodies was used.     

Glucose concentration in the vitreous of nondiabetic and diabetic human eyes

Glycation (nonenzymatic glucosylation) of collagen may play a role in the primary pathology of the vitreous in diabetes. The extent of glycation is determined by the glucose concentration in the tissue. In this study glucose concentration was assayed in blood and vitreous samples obtained from three patient groups undergoing vitrectomy: nondiabetic patients (ND), diabetic patients with insulin-dependent diabetes mellitus (IDDM) and diabetic patients with non-insulin-dependent diabetes mellitus (NIDDM). In the ND group the glucose concentration in the vitreous (3.5 +- 1.8 mM/1) was always lower than in the blood (9.1 +- 3.5 mM/1). In the diabetic groups the vitreous glucose concentration was, with a few exceptions, generally lower than the blood glucose concentration. The vitreous glucose concentration in these groups was generally higher (IDDM 9.4+-3.3 mM/1, NIDDM 7.2+-3.9 mM/1) than in the ND group, and in 15 specimens exceeded 11 mM/1, a level increasing the probability of collagen glycation in the vitreous of diabetic patients.This study was given financial support by the Herman Järnhardt Foundation, the Inez and Joel Carlsson Foundation and by Diabetesföreningen in Malmö     

Monitoring left ventricular dilation in mice with PET.

Molecular imaging by small-animal PET is an important noninvasive means to phenotype transgenic mouse models in vivo. When investigating pathologies of the left ventricular (LV) myocardium, the serial assessment of LV volumes is important. By this, the presence of LV dilation as a sign of developing heart failure can be detected. Whereas PET is usually used to derive biochemical and molecular information, functional parameters such as ventricular volumes are generally measured using echocardiography or MRI. In this study, a novel method to monitor LV dilation in mice with PET is presented and evaluated using cardiac MRI. METHODS: A semiautomatic 3-dimensional algorithm was used to delineate the LV myocardial wall on static PET images depicting myocardial glucose metabolism ((18)F-FDG PET) for 20 mice: 10 wild-type and 10 genetically modified littermates designed to develop a dilative cardiomyopathy phenotype (cardiomyocyte-specific knockout of survivin). The volume enclosed by the 3-dimensional midmyocardial contour was calculated as a measure for LV volume for each mouse. Data were compared with ventricular volumes measured by MRI in the same animals. RESULTS: LV volumes obtained by PET and MRI correlated well (R = 0.89) for hearts with small and large left ventricles. In accordance with the hypothesis, the LV volumes were increased significantly for transgenic mice examined at an older age compared with those examined at a younger age (MRI: 160.5 +/- 25.7 microL vs. 114.7 +/- 15.2 microL [P = 0.012]; PET: 129.3 +/- 15.3 microL vs. 73.8 +/- 15.0 microL [P < 0.001], all values shown as mean +/- SD; for MRI, mean of end-diastolic and end-systolic volumes are given), whereas they did not for their wild-type littermates (MRI: 106.2 +/- 12.3 microL vs. 94.7 +/- 14.6 microL [P = 0.214]; PET: 82.6 +/- 20.9 microL vs. 65.0 +/- 16.9 microL [P = 0.185]). CONCLUSION: Evaluation and quantitation of LV dilation in both control and cardiomyopathic mice can be reliably and serially performed using small-animal PET and (18)F-FDG, yielding useful functional information in addition to metabolic data.