Umbelliferone attenuates glycerol-induced myoglobinuric acute kidney injury through peroxisome proliferator-activated receptor-γ agonism in rats.

Rhabdomyolysis is a clinical syndrome caused by damage to skeletal muscle, which consequently releases breakdown products into circulation and causes acute kidney injury (AKI) in humans. Intramuscular injection of glycerol mimics rhabdomyolysis and associated AKI. In this study, we explored the role of umbelliferone against glycerol-induced AKI in rats. Kidney function was assessed by measuring serum creatinine, urea, electrolytes, and microproteinuria. Renal oxidative stress was quantified using thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione assay. Renal histological changes were determined using periodic acid Schiff and hematoxylin-eosin staining, and immunohistology of apoptotic markers (Bax, Bcl-2) was done. Serum creatine kinase was quantified to assess glycerol-induced muscle damage. Umbelliferone attenuated glycerol-induced change in biochemical parameters, oxidative stress, histological alterations, and renal apoptosis. Pretreatment with bisphenol A diglycidyl ether, a peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist, attenuated umbelliferone-mediated protection. It is concluded that umbelliferone attenuates glycerol-induced AKI possibly through PPAR-γ agonism in rats.

Cervical dysplasia in a patient with inherited epidermodysplasia verruciformis-A mere coincidence?

Epidermodysplasia verruciformis (EV) is a rare inherited or acquired genodermatosis caused by increased susceptibility to infection by the beta subtypes of human papillomavirus (HPV). The co-occurrence of EV with high-risk (HR) HPV infection leading to cervical dysplasia is unreported in the literature to date. We report a patient with inherited EV who developed extensive anogenital and cervical dysplasia linked to concurrent HR-HPV infection. Literature review suggests that there is a negative correlation of cervical dysplasia and cervical cancer with EV, which suggests that this patient's presentation and course are exceptional.

Stevioside protects against rhabdomyolysis-induced acute kidney injury through PPAR-γ agonism in rats.

We explored the potential role of peroxisome proliferator activated receptor-γ (PPAR-γ) in stevioside-mediated renoprotection using rhabdomyolysis-induced acute kidney injury (AKI) model in rats. Rhabdomyolysis refers to intense skeletal muscle damage, which further causes AKI. Glycerol (50% w/v, 8 ml/kg) was injected intramuscularly in rats to induce rhabdomyolysis. After 24 hr, AKI was demonstrated by quantifying serum creatinine, urea, creatinine clearance, microproteinuria, and electrolytes in rats. Further, oxidative stress was measured by assaying thiobarbituric acid reactive substances, generation of superoxide anion, and reduced glutathione levels. Additionally, serum creatine kinase (CK) level was assayed to determine glycerol-induced muscle damage in rats. Pathological changes in rat kidneys were studied using hematoxylin-eosin and periodic acid Schiff staining. Moreover, the expression of apoptotic markers (Bcl-2, Bax) in rat kidneys was demonstrated by immunohistochemistry. Stevioside (10, 25, and 50 mg/kg) was administered to rats, prior to the induction of AKI. In a separate group, bisphenol A diglycidyl ether (BADGE, 30 mg/kg), a PPAR-γ receptor antagonist was given prior to stevioside administration, which was followed by rhabdomyolysis-induced AKI in rats. The significant alteration in biochemical and histological parameters in rats indicated AKI, which was attenuated by stevioside treatment. Pretreatment with BADGE abrogated stevioside-mediated renoprotection, which is suggestive of the involvement of PPAR-γ in its renoprotective effect. In conclusion, stevioside protects against rhabdomyolysis-induced AKI, which may be attributed to modulation of PPAR-γ expression.

Advances in Monitoring and Prognostication for Lymphoma by Flow Cytometry.

Flow cytometry (FC) is a well-established method important in the diagnosis and subclassification of lymphoma. In this article, the role of FC in lymphoma prognostication will be explored, and the clinical role for FC minimal/measurable residual disease testing as a monitoring tool for mature lymphoma will be introduced. Potential pitfalls of monitoring for residual/recurrent disease following immunotherapy will be presented.

Benign Histiocyte-Rich Pseudotumor Developing Postchemotherapy and Mimicking Residual Disease.

Histiocyte-rich pseudotumors (HRPT) developing postchemoradiation therapy are a florid response to treatment and reparative change. Although these are benign processes, clinically and radiologically, these may mimic recurrent/relapsed disease. We describe a case of an adult male with history of diffuse large B-cell lymphoma (DLBCL), status postchemoradiation therapy, who developed HRPT at the site of original involvement, mimicking relapse of disease on positron emission tomography/computed tomography (PET/CT) imaging. This is one of the few reported cases of posttreatment HRPT. This entity is important to point out the limitations of PET/CT imaging in patients with lymphomas and metastatic disease and stresses the importance of an excisional biopsy for determining relapse and the need for further treatment.

PHISTc protein family members localize to different subcellular organelles and bind Plasmodium falciparum major virulence factor PfEMP-1.

Plasmodium falciparum encodes a novel repertoire of the Plasmodium helical interspersed subtelomeric (PHIST) family of exported proteins, which play diverse roles in infected red blood cells, contributing to malaria pathogenesis. PHIST proteins are central to parasite biology and modify human erythrocytes by interacting with parasite and host proteins. Here, we have attempted to understand the localization and function of two unexplored proteins of the PHISTc subfamily, PFD1140w and PF11_0503, and compared these with a well-characterized member, PFI1780w. We demonstrate that Phist domains assume different oligomeric states owing to a distinct array of subunit interface residues. Colocalization of a Maurer's cleft signature protein, P. falciparum skeleton-binding protein-1 (PfSBP-1), and P. falciparum erythrocyte membrane protein-1 (PfEMP-1) revealed different subcellular destinations for these PHIST members. We further show the binding of recombinant PHIST proteins to the cytoplasmic tail of PfEMP-1 and a novel interaction with PfSBP-1. Interestingly, PFD1140w interacts with PfEMP-1 and PfSBP-1 simultaneously in vitro leading to formation of a complex. These two distant PHISTc members also bind PfEMP-1 on distinct sites, despite sharing the Phist domain. Our data re-emphasize a supportive role for PHIST proteins in cytoadhesion, and identify a new binding partner, PfSBP-1, for members of this family. This information therefore adds another chapter to the understanding of P. falciparum biology and highlights the significance of the unexplored PHIST family.