Current medicinal chemistry
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Temperature control, airway management and support of circulation remain the gold-standards for the majority of neonates requiring resuscitation at birth. For the minority of neonates in which the basic steps of resuscitation fail to reverse an adverse situation, drug administration is justifiable. The 2010 International Liaison Committee on Resuscitation (ILCOR) guidelines for newborn resuscitation state: "Drugs are rarely indicated in resuscitation of the newly born infant. ⋯ These are best given via an umbilical venous catheter". Even though drugs have been used in neonatal resuscitation for long, their doses, order and route of administration have been issues of debate among neonatologists, mainly due to the lack of data in human studies. This review will examine existing evidence behind the medications currently used in neonatal resuscitation.
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microRNAs (miRNAs) are 21-22 nucleotide non-coding RNAs that regulate gene expression and play fundamental roles in biological processes. These small molecules bind to target mRNAs, leading to translational repression and/or mRNA degradation. Aberrant miRNA expression is associated with several human diseases such as cancer, cardiovascular disorders, inflammatory diseases and gynecological pathology. ⋯ Recently, miRNAs have been detected in serum and plasma, and circulating miRNA expression profiles have now been associated with a range of different tumor types. Their accessibility in peripheral blood and stability given the fact that miRNAs circulate confined within exosomes, make researchers foster hope in their role as emerging biomarkers of cancer and other disorders. The development of therapies that might block the expression or mimic the functions of miRNAs could represent new therapeutic strategies for any of the aforementioned gynecological disorders.
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Glutamate has been implicated in the pathogenesis of several diseases on the central nervous system, but recent studies have also suggested that it can be involved also in the onset and course of peripheral neuropathies. Given the increasing evidence of this possibility, several attempts have been performed in order to modulate its activity. Among them, glutamate carboxypeptidase II (GCP II) inhibition demonstrated promising results in different models of peripheral nerve damage, including diabetic and toxic neuropathies.
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Deeper understanding of DNA repair mechanisms and their potential value as therapeutic targets in oncology heralded the clinical development of poly(ADP-ribose) polymerase (PARP) inhibitors. Although initially developed to exploit synthetic lethality in models of cancer associated with defective DNA repair, our burgeoning knowledge of PARP biology has resulted in these agents being exploited both in cancer with select chemotherapeutic agents and in non-malignant diseases. In this review article, we briefly review the mechanisms of DNA repair and pre-clinical development of PARP inhibitors before discussing the clinical development of the various PARP inhibitors in depth.
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Lung injuries that impact the alveolus, such as emphysema, pulmonary fibrosis, and acute lung injury, are costly and prevalent problems. Moreover, the extent of alveolar injury and impairment of gas exchange is strongly associated with prognosis and survival. ⋯ Techniques to explore selfrenewal and multipotency have been rigorously applied to these putative stem-progenitor cell populations and the data thus far is compelling. This review provides background to the study of alveolar regeneration with the aim to provide context to the recent discoveries of putative stem-progenitor cells that may contribute to this process.