Cranberry proanthocyanidins are cytotoxic to human cancer cells and sensitize platinum‐resistant ovarian cancer cells to paraplatin

Polyphenolic extracts of the principal flavonoid classes present in cranberry were screened in vitro for cytotoxicity against solid tumor cells lines, identifying two fractions composed principally of proanthocyanidins (PACs) with potential anticancer activity. Matrix‐Assisted Laser Desorption/Ionization Time‐Of‐Flight Mass Spectrometry (MALDI‐TOF‐MS) analysis of the proanthocyanidins (PACs) fractions indicated the presence of A‐type PACs with 1–4 linkages containing between 2–8 epicatechin units with a maximum of 1 epigallocatechin unit. PACs exhibited in vitro cytotoxicity against platinum‐resistant human ovarian, neuroblastoma and prostate cancer cell lines (IC₅₀ = 79–479 µg/mL) but were non‐cytotoxic to lung fibroblast cells (IC₅₀ > 1000 µg/ml). SKOV‐3 ovarian cancer cells treated with PACs exhibited classic apoptotic changes. PACs acted synergistically with paraplatin in SKOV‐3 cells. Pretreatment of SKOV‐3 cells with PACs (106 µg/ml) resulted in a significant reduction of the paraplatin IC₅₀ value. Similarly, in a BrdU incorporation assay, co‐treatment of SKOV‐3 cells with PACs and paraplatin revealed reduced cell proliferation at lower concentrations than with either individually. In SKOV‐3 cell cultures co‐treated with PAC‐1 and paraplatin, an HPLC analysis indicated differential quantitative presence of various PAC oligomers such as DP‐8, ‐9, ‐11 and ‐14 indicating either selective binding or uptake. Cranberry proanthocyanidins exhibit cell‐line specific cytotoxicity, induce apoptotic markers and augment cytotoxicity of paraplatin in platinum‐resistant SKOV‐3 ovarian cancer cells. Copyright © 2009 John Wiley & Sons, Ltd.     

Hyperglycemia in COVID-19 infection without diabetes mellitus: Association with inflammatory markers

BACKGROUND New onset hyperglycemia is common in patients with severe coronavirus disease 2019(COVID-19) infection. Cytokine storm due to COVID-19 infection is an essential etiology for new-onset hyperglycemia, but factors like direct severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-induced pancreatic β-cell failure have also been postulated to play a role.AIM We plan to investigate further the mechanisms underlying SARS-CoV-2 infectioninduced hyperglycemia, particularly the rationale ...     

Anti-arthritic activity of boswellic acids in bovine serum albumin (BSA)-induced arthritis

The effect of boswellic acids on bovine serum albumin (BSA)-induced arthritis in rabbits was studied. Oral administration of boswellic acids (25, 50 and 100 mg/kg/day) significantly reduced the population of leucocytes in a BSA-injected knee and changed the electrophoretic pattern of the synovial fluid proteins. The local injection of boswellic acids (5, 10 and 20 mg) into the knee 15 min prior to BSA challenge also significantly reduced the infiltration of leucocytes into the knee joint, reduced the infiltration of leucocytes into the pleural cavity and inhibited the migration of PMN in vitro. The leucocyte-inhibitory activity of boswellic acids was not due to its cytotoxic effect. The boswellic acids did not show any detergent or surfactant properties.     

‘Hints’ in the horn: diagnostic clues in the stratum corneum

The stratum corneum or horny layer is the uppermost layer of the epidermis, and is mainly responsible for the skin's barrier function. In spite of its complexity at the ultrastructural and molecular level, the features accessible to visualization on conventional histology are relatively limited. Nevertheless, knowledge of subtle clues that one may observe in the stratum corneum can prove useful in a wide range of situations in dermatopathology. We herein review a selection of common and rare entities in which the horny layer may reveal significantly important hints for the diagnosis. These clues include parakeratosis and its different patterns (focal, confluent, alternating, associated with spongiosis, epidermal hyperplasia or lichenoid changes), subcorneal acantholysis, infectious organisms in the stratum corneum (including fungal, bacterial and parasitic), thickening or thinning of the stratum corneum and the presence of different kinds of pigment. Even when normal, the horny layer may prove to be useful when seen in association with severe epidermal damage, a combination of features testifying to the acute nature of the underlying pathological process.     

Bacteremias in liver transplant recipients: shift toward gram-negative bacteria as predominant pathogens.

During the 1990s, gram-positive bacteria emerged as major pathogens after liver transplantation. We sought to determine whether the pathogens associated with bacteremias in liver transplant recipients have changed. Patients included 233 liver transplant recipients transplanted between 1989 and 2003. The proportion of all infections due to bacteremias increased significantly over time (P <.0001). Of other major infections, a trend toward a decrease in fungal infections (P =.089) and a significant decrease in cytomegalovirus (CMV) disease (P =.0004) were documented. Whereas the proportion of bacteremias due to gram-negatives increased from 25% in the period of 1989-1993 to 51.8% in 1998-03, that of gram-positive bacteria decreased from 75% in the period of 1989-93 to 48.2% in the period of 1998-2003. Methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most frequent pathogens in bacteremic patients. The incidence of bacteremias due to MRSA and Pseudomonas aeruginosa has remained unchanged (P <.20); however, that due to enteric gram-negative bacteria, particularly Klebsiella pneumoniae has increased (P =.02). Klebsiella pneumoniae isolates in the current quartile were not clonally related. In conclusion, bacteremias as a proportion of all infections in liver transplant recipients have increased significantly over time, due in part to a decline in infections due to other major pathogens, e.g., fungi, primarily Candida species, and CMV. Gram-negative bacteria have emerged as predominant pathogens in bacteremic liver transplant recipients.     

One-stage repair of cardiac and arch anomalies without circumlatory arrest

Indian Journal of Thoracic and Cardiovascular Surgery -