Charlespilegaard3229

A clinical trial done by Schimmer et al resulted in poor outcomes which prompted studies on alternative clioquinol-based applications, such as new combinations, new delivery methods, or new clioquinol-derived analogues. In addition, numerous patents claim alternative uses of clioquinol for cancer therapy. CONCLUSION Clioquinol exhibits anti-cancer activities in many cancer types preclinically. Low therapeutic efficacy in a clinical trial has prompted new studies that aim in discovering more effective clioquinol-based cancer therapies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.BACKGROUND Inflammatory process is one of the mechanisms by which our body upholds us from pathogens such as parasites, bacteria, viruses, and other harmful microorganisms. Inflammatory stimuli activate many intracellular signaling pathways such as nuclear factor-kB (NF-kB) pathway and three mitogen-activated protein kinase (MAPK) pathways which are mediated through extracellular-signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38. The p38 has evolved as an enticing target in treating many persistent inflammatory diseases. Hence, designing novel p38 inhibitors targeting MAPK pathways has acquired significance. OBJECTIVE Peruse to identify the lead target to discover novel p38MAPK inhibitors with different scaffolds having improved selectivity over the prototype drugs. METHODS Structure and the binding sites of p38MAPK were focused. Various scaffolds designed for inhibition and the molecules which have entered the clinical trials are discussed. RESULTS This review aspires to present the available information on the structure and the 3D binding sites of p38MAPK, various scaffolds designed for imidazole, urea, benzamide, azoles, quinoxaline, chromone, ketone as a potent p38MAPK inhibitors and their SAR studies and the molecules which have entered the clinical trials. CONCLUSION Development of successful selective p38MAPK inhibitors in inflammatory diseases are in progress despite of all challenges. It was speculated that p38MAPK also plays an important role in treating diseases such as neuroinflammation, arterial inflammation, vascular inflammation, cancer and so on which are posing the world with treatment challenges. In this review, clinical trials of drugs are discussed related to inflammatory and its related diseases. Research is in progress to design and develop novel p38MAPK inhibitors with minimal side effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.BACKGROUND In HIV negative population metabolic syndrome and steatosis are related to poorer neurocognitive (NC) performance. We set out to find if similar relation exists in people living with HIV (PLWH). METHODS we included male PLWH aged 20-65, with undetectable viral load for at least 6 months. Data on levels of education, anthropometric measurements, CD4 levels, ART, markers of metabolic syndrome, smoking and concurrent treatment were collected from database. Concentrations of TNF-α and IL-6 were measured. An ultrasound was used to establish the presence of steatosis, visceral fat thickness and carotid intima media thickness. An extensive NC assessment was done by an experienced neuropsychologist. Cognitive domains were defined as executive functions, divergent reasoning, visuo-constructional abilities, delayed recall and working memory and learning and were measured using a battery of 12 tests. RESULTS 88 PLWH were included (mean age 39,9 years), 51% on PIs, 46% on NNRTI; 20,4% had metabolic syndrome, 42% patients had steatosis. Weak but statistically significant negative correlations were found between the presence of metabolic syndrome, steatosis and VFT and cognitive domains (divergent reasoning, delayed recall and working memory). Poorer perfomrance in the domains of divergent reasoning and in the working memory were found in participants with steatosis (p=0,048 and 0,033 respectivly). CONCLUSION Although the sample size was relatively small our results show consistent correlations between the observed neurocognitive variables and metabolic parameters. As central obesity is one of the contributors to NCI it would be one of the modifiable factors to prevent further neurocognitive decline. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.General anesthetics are a class of drugs that target the central nervous system and are widely used for various medical procedures. General anesthetics produce many behavioral changes required for clinical intervention including amnesia, hypnosis, analgesia, and immobility; while may also induce side effects like respiration and cardiovascular depressions. Understanding the mechanism of general anesthesia is essential for the development of selective general anesthetics which can preserve wanted pharmacological actions and exclude the side effects and underlying neural toxicities. However, the exact mechanism of how general anesthetics work is still elusive. Various molecular targets have been identified as specific targets for general anesthetics. Among these molecular targets, ion channels are the most principal category, including ligand gated ionotropic receptors like γ-aminobutyric acid, glutamate and acetylcholine receptors, voltage-gated ion channels like voltage-gated sodium channel, calcium channel and potassium channels, and some second massager coupled channels. For neural functions of the central nervous system, synaptic transmission is the main procedure for which information is transmitted between neurons through brain regions, and intact synaptic function is fundamentally important for almost all the nervous functions including consciousness, memory, and cognition. IDF-11774 ic50 Therefore, it is important to understand the effects of general anesthetics on synaptic transmission via modulations of specific ion channels and relevant molecular targets, which can lead to the development of safer general anesthetics with selective actions. The present review will summarize the effects of various general anesthetics on synaptic transmissions and plasticity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.