Management of immune cytopenias in patients with systemic lupus erythematosus — Old and new

There are various immune cytopenias associated with systemic lupus erythematosus (SLE). The most common one is anemia; however, there are different etiologies for the anemia caused by SLE. Anemia could be due to chronic disease, secondary to renal insufficiency, blood loss, drug induced or autoimmune hemolysis. There are other very rare causes of anemia secondary to SLE which include red cell aplasia, aplastic anemia, and microangiopathic hemolytic anemia. Treatment of the anemia would be according to the cause. Leukopenia, neutropenia, and lymphopenia are hematologic complications associated with SLE, and in majority of cases no treatment is required. Thrombocytopenia is one of the complications of SLE and is usually treated by steroids. However, there are significant numbers of patients which will either not respond to or relapse after treatment. This article summarizes immune cytopenias seen in patients with SLE, and it also discusses management of these cytopenias.     

Targeting TGFbeta signaling for cancer therapy

Transforming growth factor (TGF) betas are multifunctional polypeptides that regulate several cellular functions, including cell growth and differentiation, extra cellular matrix production, motility and immunosuppression. The growth-inhibiting properties of TGFbeta have gained much attention into its role as a tumor suppressor. There is, however, now increasing evidence that TGFbeta switches roles, from tumor suppressor to tumor promoter, as the tumor progresses. Given the integral role of TGFbeta in the tumor progression, it follows that TGFbeta signaling offers an attractive target for cancer therapy. Several strategies including the use of antisense oligonucleotides for TGFbeta, TGFbeta antibodies, dominant negative TGFbeta receptor II, and small drug-molecules to inhibit TGFbeta receptor I kinase have shown great promise in the preclinical studies. These new findings, coupled with progressing clinical trials indicate that inhibition of TGFbeta signaling may, indeed, be a viable option to cancer therapy. This review summarizes the TGFbeta signaling, the dual role of TGFbeta--as a tumor suppressor and tumor promoter, and various strategies targeted against TGFbeta signaling for cancer therapy. The next few years promise to better our understanding of approaching cancer therapy with an eye to the inhibition of TGFbeta signaling.     

Curcumin reduces the expression of interleukin 1β and the production of interleukin 6 and tumor necrosis factor alpha by M1 macrophages from patients with Behcet's disease

Objective: Behcet's disease (BD) is an auto-inflammatory disorder. Curcumin as a bio-active agent has anti-inflammatory properties. Effects of curcumin on the pathogenesis of BD are still not clear. In this study, we investigated the effect of curcumin on the inflammatory cytokines expression and production in M1 macrophages from BD patients compared with healthy controls.

Methods: Monocytes were collected from 10 healthy controls and 20 active BD patients, differentiated to macrophages by macrophage-colony stimulating factor for 7?d. Macrophages were then treated with interferon gamma, lipopolysaccharide, and curcumin (10 or 30?µg/ml) for 24?h. Analysis of tumor necrosis factor-alpha (TNFα), interleukin 1β (IL-1β), and IL-6 mRNA expression and protein production was performed using SYBR Green qPCR and ELISA method.

Results: Treatment with 30?µg/ml curcumin significantly down-regulated mRNA expression of IL-1β (p?<?.05) and protein production of IL-6 (p?p?p?Conclusions: We demonstrated that curcumin can inhibit the expression and production of inflammatory cytokines in M1 macrophages from BD patients. Our results suggest that curcumin can modulate inflammatory signaling more specifically in macrophages from BD patients than healthy macrophages.     

Functionalized Magnetonanoparticles in Visualization of Intracranial Tumors on MRI

Purpose

The development of nonradioactive and targeted magnetonanoparticles (MNP) capable of crossing the blood–brain barrier (BBB) and of concentrating in and enhancing the contrast of intracranial tumors on magnetic resonance imaging (MRI).

Procedure

Nonradioactive 2-deoxy-d-glucose (2DG) was covalently attached to magnetonanoparticles composed of iron oxide and dextran and prepared for intravenous (tail) injection in the naïve rats and mouse models of glioma. MR images were acquired at 3 and 7 T.

Results

2DG-MNP increased tumor visibility and improved delineation of tumor margins. Histopathology confirmed that 2DG-MNP crossed the BBB and accumulated within brain parenchyma.

Conclusion

Nonradioactive 2DG-MNP can cross an intact BBB on and improve visualization of tumor and tumor margins on MRI.     

Eosinophilic pulmonary syndrome as a manifestation of GVHD following hematopoietic stem cell transplantation in three patients

Eosinophilic pulmonary syndrome is an uncommon problem in SCT recipients that can mimic an infectious process. We report the occurrence of eosinophilic pulmonary syndrome in three patients following allogeneic hematopoietic stem cell transplantation (HSCT), and postulate that this entity is part of the clinicopathologic spectrum of pulmonary GVHD. In all three cases, active chronic GVHD of the skin preceded or coincided with the development of pulmonary involvement. Other common features included peripheral blood eosinophilia, diffuse bilateral pulmonary infiltrates and lung biopsies showing pronounced infiltrates of eosinophils involving the small bronchioles. All patients responded promptly to systemic steroid therapy, with improvement of their pulmonary symptoms and the resolution of peripheral blood eosinophilia. Clinicians should be aware that eosinophilic pulmonary syndrome can occur following HSCT, may be associated with other manifestations of chronic GVHD, and generally responds well to corticosteroid therapy.     

Imaging brain neuronal activity using functionalized magnetonanoparticles and MRI

This study explored the use of non-radioactive 2-deoxy glucose (2DG)-labeled magnetonanoparticles (MNP) and magnetic resonance imaging (MRI) to detect functional activity during rest, peripheral stimulation, and epileptic seizures, in animal models. Non-radioactive 2DG was covalently attached to magnetonanoparticles composed of iron oxide and dextran and intravenous (tail) injections were performed. 2DG-MNP was injected in resting and stimulated na?ve rodents and the subsequent MRI was compared to published (14)C-2DG autoradiography data. Reproducibility and statistical significance was established in one studied model. Negative contrast enhancement (NCE) in acute seizures and chronic models of epilepsy were investigated. MRI NCE due to 2DG-MNP particles was compared to that of plain (unconjugated) MNP in one animal. NCE due to 2DG-MNP particles at 3?T, which is approved for human use, was also investigated. Histology showed presence of MNP (following intravenous injection) in the brain tissues of resting na?ve animal. 2DG-MNP intraparenchymal uptake was visible on MRI and histology. The locations of NCE agreed with published results of 2DG autoradiography in resting and stimulated animals and epileptic rats. Localization of epileptogenicity was confirmed by subsequent depth-electrode EEG (iEEG). Non-radioactive 2DG-MNP can cross the blood-brain barrier (BBB) and may accurately localize areas of increased activity. Although, this proof-of-principle study involves only a limited number of animals, and much more research and quantification are necessary to demonstrate that 2DG-MNP, or MNPs conjugated with other ligands, could eventually be used to image localized cerebral function with MRI in humans, this MNP-MRI approach is potentially applicable to the use of many bioactive molecules as ligands for imaging normal and abnormal localized cerebral functions.     

A Model for Frequency Dependence of Conductivities of the Live Human Skull

A mathematical model (() A, where, conductivity, =2f applied frequency (Hz), A (amplitude) and (unitless) search parameters) was used to fit the frequency dependence of electrical conductivities of compact, spongiosum, and bulk layers of the live and, subsequently, dead human skull samples. The results indicate that the fit of this model to the experimental data is excellent. The ranges of values of A and were, spongiform (12.0-36.5, 0.0083-0.0549), the top compact (5.02-7.76, -0.137-0.0144), the lower compact (2.31-10.6, 0.0267-0.0452), and the bulk (7.46-10.6, 0.0133-0.0239). The respective values A and for the respective layers of the dead skull samples were (40.1-89.7, -0.0017-0.0287), (5.53-14.5, -0.0296 - -0.0061), (4.58-15.9, -0.0226-0.0268), and (12.7-25.3, -0.0158-0.0132).     

A newly developed removable dental device for fused 3-D MRI/MEG Imaging

Recently 3-D imaging techniques have been used to shed light on the role of abnormal brain functions in such conditions as nocturnal bruxism and orofacial pain. In order to achieve precise 3-D image fusion between magnetic resonance images (MRI) and magnetoencephalography (MEG) data, we developed a removable dental device which attaches rigidly to the teeth. Using this device, correlation of MEG and MRI data points was achieved by the co-registration of 3 or more fiducial points. Using a Polhemus 3-space digitizer the locations of the points were registered on MEG and then a small amount of high-water-content material was placed at each point for registering these same points on MRI. The mean reproducibility of interpoint distances, determined for 2 subjects, was between 0.59 and 0.82 mm. Using a Monte Carlo statistical analysis we determined that the accuracy of a posterior projection from the fiducial points to any point within the strata of the brain is ±3.3 mm. The value of this device is that it permits reasonably precise and repeatable co-registration of these points and yet it is easily removed and replaced by the patient. Obviosly such a device could also be adapted for use in diagnosis and analysis of brain functions related with other various sensory and motor functions (e.g. taste, pain, clenching) in maxillofacial region using MRI and MEG.