Administration of rIL-33 Restores Altered mDC/pDC Ratio, MDSC Frequency, and Th-17/Treg Ratio during Experimental Cerebral Malaria.

The onset of malaria causes the induction of various inflammatory markers in the host's body, which in turn affect the body's homeostasis and create several cerebral complications. Polarization of myeloid-derived suppressor cells (MDSCs) from the classically activated M1 to alternatively activated M2 phenotype increases the secretion of pro-inflammatory molecules. Treatment with recombinant IL-33 (rIL-33) not only alters this MDSC's polarization but also targets the glycolysis pathway of the metabolism in MDSCs, rendering them less immunosuppressive. Along with that, the Helper T-cells subset 17 (Th17)/T regulatory cells (Tregs) ratio is skewed towards Th17, which increases inflammation by producing more IL-17. However, treating with rIL-33 also helps to restore this ratio, which brings back homeostasis. During malaria infection, there is an upregulation of IL-12 production from dendritic cells along with a distorted myeloid dendritic cells (mDC)/plasmacytoid dendritic cells (pDC) ratio towards mDCs promoting inflammation. Administering rIL-33 will also subvert this IL-12 production and increase the population of pDC in the host's immune system during malaria infection, thus restoring mDC/pDC to homeostasis. Therefore, treatment with rIL-33 to reduce the pro-inflammatory signatures and maintenance of immune homeostasis along with the increase in survivability could be a potential therapeutic approach for cerebral malaria.

Giant Scrotal Lymphoedema: A Case Series.

Giant scrotal lymphoedema is a rare condition caused by obstruction, aplasia, or hypoplasia of lymphatic vessels draining the external genitalia. While this condition can be congenital or acquired, the most common acquired cause of such lymphatic obstruction worldwide is lymphatic filariasis (LF). We present a case series analysis of three patients of giant scrotal lymphoedema who were successfully treated for the condition in the Department of General Surgery, King George's Medical University (KGMU), Lucknow, with satisfactory post-operative recovery and minimal recurrence. The first patient was a 45-year-old who had been living with the condition for 10 years, and the resected scrotal tissue weighed 35 kg. The second patient was a 45-year-old who was diagnosed with filariasis five years back before the condition set in, and the resected scrotal tissue weighed 32 kg. The third patient was a 22-year-old young man who had been diagnosed with the condition 10 years back, and the resected scrotal tissue weighed 25 kg. Proper pre-operative evaluation was conducted in all three patients to establish the diagnosis of scrotal lymphoedema. The urethral catheterisation was conducted, which additionally helped to identify penile tissue intraoperatively. Careful exploration of scrotal tissue was conducted along with delineation of the penis from scrotal oedema. The surgical approach involved debulking scrotal lymphoedema with the reconstruction of scrotal skin while preserving penile tissue. Patients with giant scrotal lymphoedema face the social stigma that creates physical disability. Hence, they end up seeking medical help from tertiary care centres after the disease has reached advanced stages and fibrosis has set in. However, single-stage debulking, along with reconstructive surgery (referred to as reduction scrotoplasty), yields promising results even in cases of very bulky scrotal lymphoedema, weighing up to 35 kg, as per our study.

Administration of soluble gp130Fc disrupts M-1 macrophage polarization, dendritic cell activation, MDSC expansion and Th-17 induction during experimental cerebral malaria.

Regulatory effect of IL-6 on various immune cells plays a crucial role during experimental cerebral malaria pathogenesis. IL-6 neutralization can restore distorted ratios of myeloid dendritic cells and plasmacytoid dendritic cells as well as the balance between Th-17 and T-regulatory cells. IL-6 can also influence immune cells through classical and trans IL-6 signalling pathways. As trans IL-6 signalling is reportedly involved during malaria pathogenesis, we focused on studying the effects of trans IL-6 signalling blockade on various immune cell populations and how they regulate ECM progression. Results show that administration of sgp130Fc recombinant chimera protein lowers the parasitemia, increases the survivability of Plasmodium berghei ANKA infected mice, and restores the distorted ratios of M1/M2 macrophage, mDC/pDC, and Th-17/Treg. IL-6 trans signalling blockade has been found to affect both expansion of myeloid derived suppressor cells (MDSCs) and expression of inflammatory markers on them during Plasmodium berghei ANKA infection indicating that trans IL-6 signalling might regulate various immune cells and their function during ECM. In this work for the first time, we delineate the effect of sgp130Fc administration on influencing the immunological changes within the host secondary lymphoid organ during ECM induced by Plasmodium berghei ANKA infection.

Evaluation of genetic markers linked to hemophilia A locus: an Indian experience.

Hemophilia A is an X-linked recessive bleeding disorder caused by defects in factor VIII gene (F8). Our study examines variations of single nucleotide polymorphism (SNP) in F8 in the Indian population and establishes the utility of a combination of SNP and microsatellite markers for the successful identification of carriers in the affected families.