Effect of engineered superparamagnetic iron oxide nanoparticles in targeted cardiac precursor cell delivery by MRI.

A scientific approach is presented describing the fabrication of nanoprobe (GloTrack) that can act as cardiac precursor label to segregate cells from cardiac/non cardiac origins and traced by magnetic resonance imaging (MRI). Signal regulatory protein alpha (SIRPA) and kinase domain receptor (KDR) recognizing antibodies, form a layer on super paramagnetic iron oxide nanoparticle - poly-ethylene glycol (SPION-PEG) complex, and bind to protein expressed on the surface of cardiac muscle cells. Physical attributes size, distribution, labelling efficiency, echocardiogram (ECG) changes and bio-distribution by MRI were analysed. The results indicate that GloTrack has an average size of 471 nm, exhibits negative potential and promotes labelling efficiency. The bio-distribution of GloTrack in in vivo experiments was traceable in 7T MRI showing high accumulation of GloTrack in cardiac muscles as compared to the liver and spleen. ECG data revealed that GloTrack segregated cardiac precursors has the potential benefit in treating heart failure, thereby paving way in the development of minimal cell manipulation with targeted cell delivery approaches.

Safe emergency evacuation of a Tertiary Care Hospital during the "once in a century" floods in Chennai, India.

The coastal city of Chennai, India, was inundated by unprecedented heavy rains during the last week of November 2015, in what was billed as a "once in a century" floods. Over 350 people lost their lives in the floods. Global Hospital, a 250-bedded tertiary care hospital in Chennai, was heavily flooded leaving more than 100 patients and their relatives stranded inside with access totally cutoff from the rest of the world. This article describes how these patients, many in the Intensive Care Unit on ventilators, were safely managed within the hospital for over 48 h on very limited power supply and resources and then safely evacuated by fishing boats to three other city hospitals. Careful planning, anticipating hazards, identifying critical areas, effective communication and team work contributed to the successful management of this situation.

Fluorescent magnetic iron oxide nanoparticles for cardiac precursor cell selection from stromal vascular fraction and optimization for magnetic resonance imaging.

Fluorescent magnetic iron oxide nanoparticles have been used to label cells for imaging as well as for therapeutic purposes. The purpose of this study was to modify the approach to develop a nanoprobe for cell selection and imaging with a direct therapeutic translational focus. The approach involves physical coincubation and adsorption of superparamagnetic iron oxide nanoparticle-polyethylene glycol (SPION-PEG) complexes with a monoclonal antibody (mAb) or a set of antibodies. Flow cytometry, confocal laser scanning microscopy, transmission electron microscopy, iron staining, and magnetic resonance imaging were used to assess cell viability, function, and labeling efficiency. This process has been validated by selecting adipose tissue-derived cardiac progenitor cells from the stromal vascular fraction using signal regulatory protein alpha (SIRPA)/kinase domain receptor (KDR) mAbs. These markers were chosen because of their sustained expression during cardiomyocyte differentiation. Sorting of cells positive for SIRPA and KDR allowed the enrichment of cardiac progenitors with 90% troponin-I positivity in differentiation cultures. SPION labeled cardiac progenitor cells (1×10(5) cells) was mixed with gel and used for 3T magnetic resonance imaging at a concentration, as low as 12.5 µg of iron. The toxicity assays, at cellular and molecular levels, did not show any detrimental effects of SPION. Our study has the potential to achieve moderate to high specific cell selection for the dual purpose of imaging and therapy.

A study on FoxP3 and Tregs in paired samples of peripheral blood and synovium in rheumatoid arthritis.

There is an increasing evidence suggesting the role of fork head boxP3 (FoxP3) in the development and the regulation of CD4(+)CD25(+) Treg cells. T-cell regulatory mechanisms in rheumatoid arthritis patients were evaluated by the contributing factors such as pro-inflammatory cytokines, circulating immune complexes, HLA DR expression, ligand binding biomarkers, FoxP3 expression in paired samples of peripheral blood (PB) and synovial fluid (SF). These cellular responses were further correlated with the humoral immune responses such as anti-cyclic citrullinated peptides IgG (CCP), circulating immune complex-c1q IgG (CIC), immunoglobulin G (IgG) and immunoglobulin M (IgM) of the rheumatoid arthritis factor (RAF). The results suggest a definitive role of Tregs in the homeostatic control because there is an increase in FoxP3 (37%) and HLA-DR (45%) expression in the synovial fluid as compared to PB. Furthermore, humoral responses as a downstream effector mechanism are positively correlated with the pathogenesis of rheumatoid arthritis (RA). A positive relationship exists between quantitative anti-CCP production and the expression of HLA-DR. The study relates an increased and pivotal role of B cell activation in the synovial fluid thereby permitting the need to ablate the targeted B cell immune responses.

Pigmented perivascular epithelioid cell tumor of the liver: report of a rare case with brief review of literature.

The perivascular epithelioid cell tumor (PEComa) family of tumors includes angiomyolipoma, lymphangioleiomyomatosis, clear cell sugar tumor of the lung, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and rare clear cell tumors of other anatomical sites (PEComas-NOS). Among the PEComas-NOS, pigmented variants are extremely rare. The case concerns a 50-year-old female who presented with pain in right hypochondrium. The resected specimen included a 24 × 18 × 9 cm mass. The tumor was histologically characterized by both spindle and epithelioid cells with round to oval nuclei and clear to eosinophilic cytoplasm containing abundant melanin pigment. The stroma demonstrated intervening, thin, fibrovascular septa. Immunohistochemically, the tumor cells were strongly positive for HMB-45, weak positive for smooth muscle actin (SMA), and negative for Hep Par 1, Glypican 3, MUM-1, and S-100 protein. The patient had no evidence of disease 24 months after surgery. Pathologists and clinicians should know about the existence of pigmented perivascular epithelioid cell tumor of the liver.

Retrospective analysis of T and B cells flow-cross matches in renal transplant recipients.

Complement-mediated cytotoxic antibodies in conventional cross match, often result in misappropriation of true positives and borderline positives which are detrimental to allograft survival. Flow cross matches (FCXM) are sensitive to capture even non complement fixing cytotoxic antibodies. This retrospective study evaluates the utility of FCXM in effectively predicting acute allograft rejection. A total of 17 cases were processed for FCXM (T and B cell) of whom seven had no rejection episodes, while the remaining 11 had acute rejection despite negative cross match and panel reacting antibodies being negative (less than 20%). The sensitivity and specificity of the FCXM outcome demonstrated that positive B-cell FCXM has potential to be a good tool in pre-transplant screening. The current analysis proposes the possible utility of B-cell positive FCXM as a more sensitive parameter in predicting acute allograft rejection prior to transplantation.