Nanotherapeutics for Treatment of Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a devastating and fatal chronic lung disease. While current pharmacotherapies have improved patient quality of life, PAH drugs suffer from limitations in the form of short-term pharmacokinetics, instability, and poor organ specificity. Traditionally, nanotechnology-based delivery strategies have proven advantageous at increasing both circulation lifetimes of chemotherapeutics and accumulation in tumors due to enhanced permeability through fenestrated vasculature. Importantly, increased nanoparticle (NP) accumulation in diseased tissues has been observed pre-clinically in pathologies characterized by endothelial dysfunction and remodeled vasculature, including myocardial infarction and heart failure. Recently, this phenomenon has also been observed in preclinical models of PAH, leading to the exploration of NP-based drug delivery as a therapeutic modality in PAH. Herein, we discussed the advantages of NPs for efficacious treatment of PAH, including heightened therapeutic delivery to diseased lungs for increased drug bioavailability, as well as highlighted innovative nanotherapeutic approaches for PAH.

Coccidioidomycosis, immunoglobulin deficiency: safety challenges with CAR T cells therapy for relapsed lymphoma.

Treatment of patients with relapsed or refractory lymphoma may require allogenic hematopoietic stem cell transplant (HSCT), but treatment of post-transplant relapse disease remains very challenging. Donor lymphocyte infusion and blinatumomab have been used with limited success for the treatment of relapse. Initial data on donor-derived CAR T cells has shown this modality to be safe and highly effective in various hematological malignancies. We present a case of a patient with highly refractory, transformed follicular lymphoma who failed both autologous and allogenic HSCT. Patient achieved long-lasting complete remission with the use of donor origin CD19 CAR T-cell therapy, without any evidence of graft-versus-host disease flare. Our patient later developed disseminated coccidioidomycosis and persistent hypogammaglobulinemia. Immunotherapy using CD19 CAR T cells can be a highly effective salvage modality, especially in cases of focal lymphoma relapse. Long-term immunosuppression secondary to B cell lymphopenia, hypogammaglobulinemia, immunoglobulin subclass deficiency, fungal infections and other infectious complications need to be monitored and promptly treated as indicated.

Age of fusion of the distal radial and ulnar epiphyses from hand radiographs-A study in Kashmiri population.

Age estimation is a crucial parameter involved in investigations pertaining to civil and criminal procedures. It also aids in various examinations in forensic medicine, pediatrics, endocrinology and radiology. One of the important methods for skeletal age estimation is the age of fusion of the epiphyses. But there occur variations in the skeletal ages due to environmental, hormonal, ethnic and other factors. Hence, there arises the need for separate standards of ossification for different regions. The present study was conducted to ascertain the age of fusion of the distal radial and ulnar epiphyses in Kashmiri population. A total of 160 healthy subjects, including 80 males and 80 females with ages ranging from 12 to 20years were studied. Their chronological age was obtained and the X-ray of their left hand was taken in the A.P view after taking the consent from their parents. The starting of epiphyseal fusion in lower end of radius in male was observed at 15-16years in 20% of the male population and for females, it was observed at 13-14years in 10% of the female population. The completion of epiphyseal fusion in lower end of radius in 100% males was noticed at 18-19years and for 100% females, it was noticed at 17-18years. The starting up of epiphyseal fusion in lower end of ulna in males was observed at 14-15years in 10% of the male population and for females, it was observed at 13-14years in 10% of the female population. The completion of epiphyseal fusion in lower end of ulna in 100% males was noticed at 18-19years and for 100% females, it was noticed at 17-18years. In case of males the age of fusion of the epiphyses of lower end of radius and lower end of ulna was found to be in the same age group 18 to 19years. Also in case of females the age of fusion of the epiphyses of lower end of radius and lower end of ulna was found to be in the same age group 17 to 18years. It was further observed that females showed fusion in advance of male subjects. The findings of this study were compared with those reported from other states of India and also from other countries.

NK cells are necessary for recovery of corneal CD11c+ dendritic cells after epithelial abrasion injury.

Mechanisms controlling CD11c(+) MHCII(+) DCs during corneal epithelial wound healing were investigated in a murine model of corneal abrasion. Selective depletion of NKp46(+) CD3- NK cells that normally migrate into the cornea after epithelial abrasion resulted in >85% reduction of the epithelial CD11c(+) MHCII(+) DCs, normally present during and after epithelial wound closure. Transfer (i.v.) of spleen NK cells into NK cell-depleted mice significantly restored levels of corneal epithelial DCs (P<0.01). Immigrated NK cells were predominately positive for IFN-γ, and topical corneal anti-IFN-γ reduced epithelial DCs by 79% (P<0.01). IFN-γ(-/-) mice had 69% fewer DCs than WT controls (P<0.01), and topical rIFN-γ applied to NK cell-depleted corneas increased epithelial DCs significantly (P<0.01). The contribution of ICAM-1, an adhesion molecule involved in leukocyte migration, expressed on healing corneal epithelium, was evaluated. ICAM-1(-/-) mice exhibited >70% reduction in epithelial DC recovery in the first 48 h after epithelial abrasion (P<0.01). These interventions reveal an early turnover of DCs in the epithelium after injury, and ICAM-1, NK cells, and IFN-γ are necessary for the immigration phase of this turnover.