Role of Clozapine in Treatment-Resistant Schizophrenia

2010 ◽  
pp. 114-128 ◽  
Author(s):  
Herbert Y Meltzer
Keyword(s):  
Treatment Resistant

scholarly journals Efficacy of Phytocannabinoids in Epilepsy Treatment: Novel Approaches and Recent Advances

2021 ◽  
Vol 18 (8) ◽  
pp. 3993
Author(s):  
Aaron M. Farrelly ◽  
Styliani Vlachou ◽  
Konstantinos Grintzalis
Keyword(s):  
Therapeutic Potential ◽  
Significant Proportion ◽  
Future Research ◽  
Specific Reference ◽  
Undesirable Side Effect ◽  
Treatment Resistant ◽  
Current Review ◽  
Epilepsy Treatment ◽  
Clinical Environments

Epilepsy is a neurological disorder mainly characterised by recurrent seizures that affect the entire population diagnosed with the condition. Currently, there is no cure for the disease and a significant proportion of patients have been deemed to have treatment-resistant epilepsy (TRE). A patient is deemed to have TRE if two or more antiepileptic drugs (AEDs) fail to bring about seizure remission. This inefficacy of traditional AEDs, coupled with their undesirable side effect profile, has led to researchers considering alternative forms of treatment. Phytocannabinoids have long served as therapeutics with delta-9-THC (Δ9-THC) receiving extensive focus to determine its therapeutic potential. This focus on Δ9-THC has been to the detriment of analysing the plethora of other phytocannabinoids found in the cannabis plant. The overall aim of this review is to explore other novel phytocannabinoids and their place in epilepsy treatment. The current review intends to achieve this aim via an exploration of the molecular targets underlying the anticonvulsant capabilities of cannabidiol (CBD), cannabidavarin (CBDV), delta-9-tetrahydrocannabivarin (Δ9-THCV) and cannabigerol (CBG). Further, this review will provide an exploration of current pre-clinical and clinical data as it relates to the aforementioned phytocannabinoids and the treatment of epilepsy symptoms. With specific reference to epilepsy in young adult and adolescent populations, the exploration of CBD, CBDV, Δ9-THCV and CBG in both preclinical and clinical environments can guide future research and aid in the further understanding of the role of phytocannabinoids in epilepsy treatment. Currently, much more research is warranted in this area to be conclusive.

Reflux aspiration associated with oesophageal dysmotility but not delayed liquid gastric emptying

2020 ◽  
Author(s):  
Oleksandr Khoma ◽  
Maite Jeanne Mendu ◽  
Amita Nandini Sen ◽  
Hans Van der Wall ◽  
Gregory Leighton Falk
Keyword(s):  
Gastric Emptying ◽  
Reflux Disease ◽  
Inclusion Criteria ◽  
Treatment Resistant ◽  
Oesophageal Motility ◽  
Oesophageal Manometry ◽  
Oesophageal Dysmotility ◽  
The Relationship ◽  
Clinical Subtype

Abstract Introduction Severe oesophageal dysmotility is associated with treatment resistant reflux and pulmonary reflux aspiration. Delayed solid gastric emptying (SGE) has been associated with oesophageal dysmotility, however the role of delayed liquid gastric emptying (LGE) in the pathophysiology of severe reflux disease remains unknown. The purpose of this study is to examine the relationship between delayed LGE, reflux aspiration and oesophageal dysmotility. Methods Data was extracted from a prospectively populated database of patients with severe treatment resistant gastro-oesophageal reflux disease (GORD). All patients with validated reflux aspiration scintigraphy (RASP) and oesophageal manometry were included in the analysis. Patients were classified by predominant clinical subtype as gastro-oesophageal (GOR) or laryngo-pharyngeal (LPR) reflux. LGE time of 22 minutes or longer was considered delayed. Results Inclusion criteria were met by 631 patients. Normal LGE time was found in 450 patients, whilst 181 had evidence of delayed LGE. Mean liquid half-clearance was 22.81min. Refux aspiration was evident in 240 patients (38%). Difference in the aspiration rates between delayed LGE (42%) and normal LGE (36%) was not significant (p=0.16). Severe ineffective oesophageal motility (IOM) was found in 70 patients (35%) and was independent of LGE time. Severe IOM was strongly associated with reflux aspiration (p<0.001). GOR dominant symptoms were more common in patients with delayed LGE (p=0.03). Conclusion Severe IOM was strongly associated with reflux aspiration. Delayed LGE is not associated with reflux aspiration or severe IOM. Delayed LGE is more prevalent in patients presenting with GOR dominant symptoms.

Clozapine: A Case Vignette

1996 ◽  
Vol 4 (6) ◽  
pp. 336-337
Author(s):  
Ilana Nayman
Keyword(s):  
Young Woman ◽  
Psychiatric Practice ◽  
Case Vignette ◽  
Treatment Resistant ◽  
Symptom Resolution ◽  
Clozapine Treatment ◽  
Level Of Functioning ◽  
History Of ◽  
High Level

This paper describes successful clozapine treatment in a young woman with a five year history of treatment-resistant schizophrenia. After various treatment-resistant strategies had been given, clozapine was commenced. Symptom resolution within 4 months and sustained high level of functioning within 7 months was achieved. The role of clozapine in general psychiatric practice is evident. Clozapine should be considered earlier in the illness course than was formerly the case.

Hypoxia induced HIF1a-mediated O-GalNAc glycosylation of cytosolic O-GlcNAcylated proteins to regulate signaling pathways in pancreatic cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15739-e15739
Author(s):  
Gerrit Wolters-Eisfeld ◽  
Baris Mercanoglu ◽  
Alina Strohmaier ◽  
Cenap Guengoer ◽  
Jakob R. Izbicki ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Tumor Development ◽  
Hek293 Cells ◽  
Treatment Resistant ◽  
Tn Antigen ◽  
Cell Energy ◽  
Hif Pathway ◽  
The Impact

e15739 Background: Hypoxia induced reprogramming of cell energy metabolism and changes in glycosylation are hallmarks of cancer promoting the induction of an invasive and treatment-resistant phenotype, triggering metastases at an early stage of tumor development. We examined the impact of hypoxia on O-GalNAc glycosylation in human HEK293, PDAC cell lines and clinical specimens. Methods: We profiled the expression of 88 glycosylation related genes by qPCR in HEK293 cells subjected to hypoxia either induced by 1% O2 or 200 mm CoCl2 identifying key O-GalNAc glycosyltransferases downregulated. Functional assays and glycoprotein analysis displayed a pronounced rate of O-GalNAc modified cytosolic proteins derived from hypoxia treated cells and PDAC specimens. Glycosidase assays could validate specificity of detection method used. Aberrant glycotype could be induced by HIF pathway activator ML 228 and inhibited using Echinomycin. PTK and STK analysis of cell lysates displayed correlation between phosphorylation and O-glycosylation in hypoxic samples. Results: Mechanistically we could show, that hypoxia induced decreased levels of C1GALT1C1 results in reduced T-Synthase activity with subsequent expression of truncated O-glycans (Tn antigen). Differential O-GalNAc glycosylation is inducible using HIF pathway activator ML228 under normoxia and the effect is reversed using 5 µM Echinomycin under hypoxia underscoring the role of HIF1a regulated transcription. Interestingly, the pattern of Tn antigen modified proteins derived from hypoxic samples differs significantly from engineered COSMC deficient cells, displaying O-GalNAc moieties in addition to O-GlcNAc in cytosolic protein fractions. Conclusions: Our findings point to a novel crosstalk of O-GalNAc and O-GlcNAcylation under hypoxia extending the knowledge base of differential O-GalNAc glycosylation in pancreatic cancer.

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