Current medicinal chemistry
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Chronic obstructive pulmonary disease (COPD) is an increasing global health problem and cause of death. COPD is a chronic inflammatory disease predominantly affecting small airways and lung parenchyma that leads to progressive airway obstruction. However, current therapies fail to prevent either disease progression or mortality. ⋯ A new promising approach is reversal of corticosteroid resistance through increasing histone deacetylase-2 (HDAC2) activity. This might be achieved by existing treatments such as theophylline, nortriptyline and macrolides, or more selectively by PI3 kinase-δ inhibitors. Thus although there have been major advances in the development of long-acting bronchodilators for COPD, it has proved difficult to find anti-inflammatory treatments that are safe and effective.
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Tuberculosis (TB), an ongoing public health threat, is worsened by the emergence of drug resistance. With an estimated 630000 cases per year of multidrug resistant (MDR)-TB, and 9% of those being extensively drug resistant (XDR)-TB, there is an urgent need for new and more effective anti-TB drugs. ⋯ In spite of the difficulties and alleged lack of interest from the pharmaceutical industry for the discovery and development of new antibiotics, several new or repurposed drugs are being evaluated in clinical trials. This review article summarizes the information available and presents an update on the drugs currently in clinical trials for TB and briefly introduces some new compounds in pre-clinical development.
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Sphingolipids are a class of lipids that have important functions in a variety of cellular processes such as, differentiation, proliferation, senescence, apoptosis and chemotherapeutic resistance. The most widely studied bioactive shingolipids include ceramides, dihydroceramide (dhCer), ceramide-1-phosphate (C1P), glucosyl-ceramide (GluCer), sphingosine and sphingosine-1-phosphate (S1P). Although the length of fatty acid chain affects the physiological role, ceramides and sphingosine are known to induce apoptosis whereas C1P, S1P and GluCer induce proliferation of cells, which causes the development of chemoresistance. ⋯ These approaches mainly aim to up-regulate the levels of apoptotic shingolipids while the proliferative ones are down-regulated, or to directly deliver cytotoxic sphingolipids like short-chain ceramide analogs to tumor cells. It is suggested that a combination therapy with conventional cytotoxic approaches while preventing the conversion of ceramide to S1P and consequently increasing the ceramide levels would be more beneficial. This review compiles the current knowledge about sphingolipids, and mainly focuses on novel agents modulating sphingolipid pathways that represent recent therapeutic strategies for the treatment of cancer.
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Controlled Clinical Trial
The role of oxidative stress in anti-tumor necrosis factor antibody treatment in Crohn's disease.
Administration of anti-tumor necrosis factor alpha antibodies [anti-TNF]-alpha represents a therapeutic approach aimed to diminish the effects of tumor necrosis factor [TNF]- alpha in Crohn's disease [CD]. Blockade of its action should be related to various changes including those in immune and inflammatory response. There is a growing body of experimental data to suggest that the chronically inflamed intestine may be subjected to considerable oxidative stress. ⋯ The levels of DIE slightly decreased in M 1 and significantly in M 5, together with the slight increase of the FOACP and SEACP in M 1 and significant increase in M 5. We conclude, that oxidative stress may be important in the pathogenesis and perpetuation of tissue injury in CD patients. The decreasing levels of DIE together with the increase of the FOCP and SEACP after infliximab treatment together with changes of markers of inflammatory activity, can participate in the improvement of clinical status of patients with CD.
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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.