Sustained remission of psychotic symptoms secondary to hypothyroidism (myxedema psychosis) after 6 months of treatment primarily with levothyroxine: a case report.

Background: Psychotic symptoms associated with hypothyroidism, also known as "myxedema psychosis," are a treatable cause of psychosis often associated with complete recovery. While most cases receive both thyroxine and a short course of antipsychotics, some reports indicate that symptoms can resolve without antipsychotic treatment, though follow-up in these cases has often been short or not reported. This is one of the first case reports demonstrating sustained remission of psychotic symptoms at 6 months in a case of myxedema psychosis treated with minimal antipsychotic medication.

Individuals to Systems: Methodological and Conceptual Considerations for Addressing Mental Illness Stigma Holistically.

Mental illness stigma is a complex public health issue that creates barriers for clients needing access to quality mental health services. Most research focuses on interpersonal stigma with emerging research examining intrapersonal and structural stigma in the healthcare setting. This commentary focuses on how to address the gaps in the existing research to elicit greater organizational/structural change in healthcare systems and positive health outcomes.

Mobile App-Based Self-Report Questionnaires for the Assessment and Monitoring of Bipolar Disorder: Systematic Review.

Background: Bipolar disorder is a chronic, progressive illness characterized by recurrent episodes of mania and depression. Self-report scales have historically played a significant role in the monitoring of bipolar symptoms. However, these tools rely on episodic memory, which can be unreliable and do not allow the clinician to monitor brief episodic symptoms or the course of symptoms over shorter periods of time.

A novel LCMSMS method for quantitative measurement of short-chain fatty acids in human stool derivatized with C- and C-labelled aniline.

A novel liquid chromatography tandem mass spectrometry (LCMSMS) method for the quantitative measurement of gut microbial-derived short-chain fatty acids (SCFAs) in human infant stool has been developed and validated. Baseline chromatographic resolution was achieved for 12 SCFAs (acetic, butyric, caproic, 2,2-dimethylbutyric, 2-ethylbutyric, isobutyric, isovaleric, 2-methylbutyric, 4-methylvaleric, propionic, pivalic and valeric acids) within an analysis time of 15min. A novel sequential derivatization of endogenous and spiked SCFAs in stool via C- and C-aniline respectively, facilitated the accurate quantitation of C-aniline derivatized endogenous SCFAs based on calibration of exogenously C-derivatized SCFAs.

Synergistic disruption of ERα/HER2 crosstalk by endoxifen and lapatinib in breast cancer cells.

Background: Despite decades of clinical success, tamoxifen therapy is complicated by inter-individual variability due to CYP450 polymorphism and resistance attributed to ERα/HER2 crosstalk. Direct administration of endoxifen shows promise in circumventing obligatory CYP450 bioactivation while maintaining efficacy. Separately, disruption of the crosstalk using probe antagonists against ERα (tamoxifen) and HER2 (e.

Evaluating Polymyxin B-Based Combinations against Carbapenem-Resistant Escherichia coli in Time-Kill Studies and in a Hollow-Fiber Infection Model.

Polymyxin B-based combinations have emerged as a mainstay treatment against carbapenem-resistant Escherichia coli (CREC). We investigated the activity of polymyxin B-based two-antibiotic combinations against CREC using time-kill studies (TKS) and validated the findings in a hollow-fiber infection model (HFIM). TKS were conducted using 5 clinical CREC strains at 5 log CFU/ml against 10 polymyxin B-based two-antibiotic combinations at maximum clinically achievable concentrations.

In Vitro Activity of Polymyxin B in Combination with Various Antibiotics against Extensively Drug-Resistant Enterobacter cloacae with Decreased Susceptibility to Polymyxin B.

Against extensively drug-resistant (XDR) Enterobacter cloacae, combination antibiotic therapy may be the only option. We investigated the activity of various antibiotics in combination with polymyxin B using time-kill studies (TKS). TKS were conducted with four nonclonal XDR E.

Phase I Metabolic Stability and Electrophilic Reactivity of 2-Phenylaminophenylacetic Acid Derived Compounds.

Diclofenac and lumiracoxib are two highly analogous 2-phenylaminophenylacetic acid anti-inflammatory drugs exhibiting occasional dose-limiting hepatotoxicities. Prior data indicate that bioactivation and reactive metabolite formation play roles in the observed toxicity, but the exact chemical influence of the substituents remains elusive. In order to elucidate the role of chemical influence on metabolism related toxicity, metabolic stability and electrophilic reactivity were investigated for a series of structurally related analogues and their resulting metabolites.

Multiple modes of inhibition of human cytochrome P450 2J2 by dronedarone, amiodarone and their active metabolites.

Dronedarone, a multiple ion channel blocker is prescribed for the treatment of paroxysmal and persistent atrial fibrillation. While dronedarone does not precipitate toxicities like its predecessor amiodarone, its clinical use has been associated with idiosyncratic hepatic and cardiac adverse effects and drug-drug interactions (DDIs). As dronedarone is a potent mechanism-based inactivator of CYP3A4 and CYP3A5, a question arose if it exerts a similar inhibitory effect on CYP2J2, a prominent cardiac CYP450 enzyme.

Metabolomic Characterizations of Liver Injury Caused by Acute Arsenic Toxicity in Zebrafish.

Arsenic is one of the most common metalloid contaminants in groundwater and it has both acute and chronic toxicity affecting multiple organs. Details of the mechanism of arsenic toxicity are still lacking and profile studies at metabolic level are very limited. Using gas chromatography coupled with mass spectroscopy (GC/MS), we first generated metabolomic profiles from the livers of arsenic-treated zebrafish and identified 34 significantly altered metabolite peaks as potential markers, including four prominent ones: cholic acid, glycylglycine, glycine and hypotaurine.

Plasma Metabonomic Profiling of Diabetic Retinopathy.

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the leading cause of visual impairment in working-age adults. Patients with diabetes often develop DR despite appropriate control of systemic risk factors, suggesting the involvement of other pathogenic factors. We hypothesize that the plasma metabolic signature of DR is distinct and resolvable from that of diabetes alone.

Prevalence of KRAS, BRAF, PI3K and EGFR mutations among Asian patients with metastatic colorectal cancer.

Mutations in oncogenes along the epidermal growth factor receptor (EGFR) signaling pathway have been implicated in the resistance to cetuximab in patients with metastatic colorectal cancer (mCRC). However, the relative significance of these mutations based on their frequencies of occurrence in the Singaporean population remains unclear. In the present study, the prevalence of Kirsten rat sarcoma viral oncogene homolog (), v-Raf murine sarcoma viral oncogene homolog B (), phosphoinositide 3-kinase () and somatic mutations were determined among Singaporean patients with mCRC.

Gastrointestinal Symptoms and Altered Intestinal Permeability Induced by Combat Training Are Associated with Distinct Metabotypic Changes.

Physical and psychological stress have been shown to modulate multiple aspects of gastrointestinal (GI) physiology, but its molecular basis remains elusive. We therefore characterized the stress-induced metabolic phenotype (metabotype) in soldiers during high-intensity combat training and correlated the metabotype with changes in GI symptoms and permeability. In a prospective, longitudinal study, urinary metabotyping was conducted on 38 male healthy soldiers during combat training and a rest period using gas chromatography-mass spectrometry.

Inactivation of Human Cytochrome P450 3A4 and 3A5 by Dronedarone and N-Desbutyl Dronedarone.

Dronedarone is an antiarrhythmic agent approved in 2009 for the treatment of atrial fibrillation. An in-house preliminary study demonstrated that dronedarone inhibits cytochrome P450 (CYP) 3A4 and 3A5 in a time-dependent manner. This study aimed to investigate the inactivation of CYP450 by dronedarone.

Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress.

"Dry eye" is a multifactorial inflammatory disease affecting the ocular surface. Tear hyperosmolarity in dry eye contributes to inflammation and cell damage. Recent research efforts on dry eye have been directed toward biomarker discovery for diagnosis, response to treatment, and disease mechanisms.

Meclizine, a pregnane X receptor agonist, is a direct inhibitor and mechanism-based inactivator of human cytochrome P450 3A.

Meclizine is an agonist of human pregnane X receptor (PXR). It increases CYP3A4 mRNA expression, but decreases CYP3A-catalyzed testosterone 6β-hydroxylation in primary cultures of human hepatocytes, as assessed at 24h after the last dose of meclizine. Therefore, the hypothesis to be tested is that meclizine inactivates human CYP3A enzymes.

Investigation of Host-Gut Microbiota Modulation of Therapeutic Outcome.

A broader understanding of factors underlying interindividual variation in pharmacotherapy is important for our pursuit of "personalized medicine." Based on knowledge gleaned from the investigation of human genetics, drug-metabolizing enzymes, and transporters, clinicians and pharmacists are able to tailor pharmacotherapies according to the genotype of patients. However, human host factors only form part of the equation that accounts for heterogeneity in therapeutic outcome.

In vitro pharmacodynamics of various antibiotics in combination against extensively drug-resistant Klebsiella pneumoniae.

Extensively drug-resistant (XDR) Klebsiella pneumoniae is an emerging pathogen in Singapore. With limited therapeutic options available, combination antibiotics may be the only viable option. In this study, we aimed to elucidate effective antibiotic combinations against XDR K.

Mechanism-based inactivation of CYP450 enzymes: a case study of lapatinib.

Mechanism-based inactivation (MBI) of CYP450 enzymes is a unique form of inhibition in which the enzymatic machinery of the victim is responsible for generation of the reactive metabolite. This precondition sets up a time-dependency for the inactivation process, a hallmark feature that characterizes all MBI. Yet, MBI itself is a complex biochemical phenomenon that operates in different modes, namely, covalent binding to apoprotein, covalent binding of the porphyrin group and also complexation of the catalytic iron.

Metabonomic profiling of bladder cancer.

Early diagnosis and life-long surveillance are clinically important to improve the long-term survival of bladder cancer patients. Currently, a noninvasive biomarker that is as sensitive and specific as cystoscopy in detecting bladder tumors is lacking. Metabonomics is a complementary approach for identifying perturbed metabolic pathways in bladder cancer.

Metabolic profiling of CHO-AβPP695 cells revealed mitochondrial dysfunction prior to amyloid-β pathology and potential therapeutic effects of both PPARγ and PPARα Agonisms for Alzheimer's disease.

In this study, we performed gas chromatography time-of-flight mass spectrometry (GC-TOFMS)-based extracellular metabolic profiling on AβPP-transfected CHO cells (CHO-AβPP695) and its wildtype. Orthogonal partial least squares discriminant analysis (OPLS-DA) was then used to identify discriminant metabolites, which gave clues on the effects of AβPP transgene on cellular processes. To confirm the hypotheses generated based on the metabolic data, we performed biochemical assays to gather further evidence to support our findings.