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Other Experimental Antiepileptic Drugs
Published in Stanley R. Resor, Henn Kutt, The Medical Treatment of Epilepsy, 2020
Gabapentin (GBP) (1-aminomethyl) cyclohexaneacetic acid, with a molecular weight of 171.24, is an amino acid with an isoelectric point of 7.14 (see structure on p. 665). It is more lipid soluble than GABA, and therefore its zwitterion penetrates the CNS to a greater extent. Although it is structurally similar to GABA, it does not bind to GABA receptors, nor does it inhibit the uptake of GABA in to synaptosomes. Therefore, it is unlikely that GBP acts directly through known GABA mechanisms.
Definition, risk factors, and epidemiology of osteoporosis
Published in Peter V. Giannoudis, Thomas A. Einhorn, Surgical and Medical Treatment of Osteoporosis, 2020
These findings support the idea that new mechanisms for the pathogenesis of osteoporosis should be considered; by determining these molecular pathways, the risk of the disease developing can be more easily detected. A subsequent differential gene expression analysis of the same population of postmenopausal women identified 3 out of 70 differentially expressed genes (signal transducer and activator of transcription 1 [STAT1]; guanylate binding protein 1 [GBP1]; and chemokine [C-X-C motif] ligand 10 CXCL10) as playing a significant role in osteoclastogenesis (63). Other less well-known mechanisms of osteoblast differentiation may also be involved in osteoporosis as a polymorphic variant of the sulfide quinone reductase-like (SQRDL) gene coding for a mitochondria protein, which catalyzes the conversion of sulfide to persulfides and has been associated with the susceptibility factor for osteoporosis in postmenopausal women (64).
Helping You Understand Dr. Goldstein's Book
Published in Katie Courmel, A Companion Volume to Dr. Jay A. Goldstein's Betrayal by the Brain, 2013
Gabapentin (GBP) acts to increase the available pool of GABA in the central nervous system and may enhance the functioning of the thalamic reticular nucleus. Symptomatically, GBP increases energy and reduces anxiety. Neurochemieally, GBP increases GABA, inhibiting an inhibitory system in the thalamic reticular nucleus (RT), resulting in thalamocortical excitation.
GBP5 Inhibition Ameliorates the Progression of Lupus Nephritis by Suppressing NLRP3 Inflammasome Activation
Published in Immunological Investigations, 2023
Naiquan Liu, Yan Gao, Ying Liu, Dajun Liu
Guanylate binding protein 5 (GBP5) belongs to the interferon gamma (IFN-γ) induced GTPase subfamily, and it displays a highly homologous and conserved GTP binding or hydrolysis domain. It has been demonstrated that GBP5 is involved in the regulation of cellular activities, such as cell differentiation signal transduction, translation and vesicle trafficking (Feng et al. 2017; Place et al. 2021). Recently, several studies have shown the proinflammatory effect of GBP5 in multiple diseases. Feng et al. have found that GBP5 participates in the innate immune response against the viral infection by inducing proinflammatory factor production (Feng et al. 2017). Furthermore, GBP5 is reported to regulate NLRP3 and AIM2 inflammasome assembly, and increased the levels of IL-1β and IL-18 (Meunier et al. 2015; Shenoy et al. 2012). Latest studies have suggested that the activation of NLRP3 inflammasome pathway is an important contributor to the LN development (Fu et al. 2017; Guo et al. 2019). Thus, we speculated that the NLRP3 inflammasome pathway might be implicated the role of GBP5 in LN.
Utility of a three-gene transcriptomic signature in the diagnosis of tuberculosis in a low-endemic hospital setting
Published in Infectious Diseases, 2023
Bih Hycenta Chendi, Tracey Jooste, Thomas Jens Scriba, Martin Kidd, Simon Mendelsohn, Kristian Tonby, Gerhard Walzl, Anne M. Dyrhol-Riise, Novel Njweipi Chegou
Of the differentially expressed genes observed in this study, Laux Da Costa et al. also identified GBP5 in a study from a similar low TB burden setting, as the best marker to discriminate between TB and other respiratory diseases (asthma and non-TB pneumonia) with an AUC of 0.92 [46]. In comparison, GBP5 had an AUC of 0.76 in the current study. GBP5 was also observed to be upregulated in TB patients and identified as a candidate for inclusion into TB biosignatures [7]. The GBP gene family has been implicated in the defence against intracellular pathogens [48] and is thought to be recruited by the interferon cytokine family [49]. Interestingly, other genes in the GBP family such as GBP1 have also been identified as potential diagnostic markers in previous TB studies [8,11,19] and thus should be investigated further.
Therapy outcome related to adalimumab trough levels in pediatric patients with inflammatory bowel disease
Published in Scandinavian Journal of Gastroenterology, 2022
Johanna Lehtomäki, Anne Nikkonen, Laura Merras-Salmio, Pauliina Hiltunen, Kaija-Leena Kolho
In adults with IBD, higher trough levels (>7.3 mg/L), but not concomitant thiopurine therapy, were associated with clinical remission, and patients with drug antibodies against adalimumab experienced treatment failure [25]. In our pediatric study, adalimumab levels above 7.5 mg/L during the first 3 months of therapy were associated with improved outcomes thereafter. It is widely recognized that loss of response is frequent during maintenance therapy with TNFα-blockers and is not always overcome with therapy escalation [9]. Therapeutic drug monitoring can be used for monitoring and guiding the dosing of different types of medications. With anti-TNF medication, drug monitoring can be used either reactively, where trough level measurements are made when loss of response is suspected, or prospectively, where optimal trough levels are pursued to prevent loss of response. Here, the therapeutic decisions and therapy adjustments were made at the discretion of the treating physician. Interestingly, a recent study identified genomic biomarkers associated with non-response in adalimumab- and infliximab-treated patients with PIBD [30]. Three genes, FCGR1A, FCGR1B, and GBP1, were found to be over-expressed in non-responders. FCRG1A and FCGR1B are expressed on the surface of neutrophils, and GBP1 is an interferon-stimulated, guanylate-binding protein involved in defense against pathogens and inflammation. This study is an example of many to come aiming at identifying non-responders at an early phase of therapy. Previously, it has also been reported that the microbiome is related to therapeutic response [31–33]. Based on these studies, it is likely that in the future drug level monitoring will be combined with testing of the microbiome and/or genetic variants when the therapeutic response is suboptimal.