Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria

Quinine remains an important anti-malarial drug almost 400 years after its effectiveness was first documented. However, its continued use is challenged by its poor tolerability, poor compliance with complex dosing regimens, and the availability of more efficacious anti-malarial drugs. This article reviews the historical role of quinine, considers its current usage and provides insight into its appropriate future use in the treatment of malaria. In light of recent research findings intravenous artesunate should be the first-line drug for severe malaria, with quinine as an alternative. The role of rectal quinine as pre-referral treatment for severe malaria has not been fully explored, but it remains a promising intervention. In pregnancy, quinine continues to play a critical role in the management of malaria, especially in the first trimester, and it will remain a mainstay of treatment until safer alternatives become available. For uncomplicated malaria, artemisinin-based combination therapy (ACT) offers a better option than quinine though the difficulty of maintaining a steady supply of ACT in resource-limited settings renders the rapid withdrawal of quinine for uncomplicated malaria cases risky. The best approach would be to identify solutions to ACT stock-outs, maintain quinine in case of ACT stock-outs, and evaluate strategies for improving quinine treatment outcomes by combining it with antibiotics. In HIV and TB infected populations, concerns about potential interactions between quinine and antiretroviral and anti-tuberculosis drugs exist, and these will need further research and pharmacovigilance

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Next-generation sequencing for research and diagnostics in kidney disease

The advent of next-generation sequencing technologies has enabled genetic nephrology research to move beyond single gene analysis to the simultaneous investigation of hundreds of genes and entire pathways. These new sequencing approaches have been used to identify and characterize causal factors that underlie inherited heterogeneous kidney diseases such as nephronophthisis and congenital anomalies of the kidney and urinary tract. In this Review, we describe the development of next-generation sequencing in basic and clinical research and discuss the implementation of this novel technology in routine patient management. Widespread use of targeted and nontargeted approaches for gene identification in clinical practice will require consistent phenotyping, appropriate disease modelling and collaborative efforts to combine and integrate data analyses. Next-generation sequencing is an exceptionally promising technique that has the potential to improve the management of patients with inherited kidney diseases. However, identifying the molecular mechanisms that lead to renal developmental disorders and ciliopathies is difficult. A major challenge in the near future will be how best to integrate data obtained using next-generation sequencing with personalized medicine, including use of high-throughput disease modelling as a tool to support the clinical diagnosis of kidney diseases