Brown and brite adipocytes: Same function, but different origin and response

Publication date: Available online 30 April 2017
Source:Biochimie
Author(s): Dinh-Toi Chu, Barbara Gawronska-Kozak
Inducing brown adipocytes in white adipose tissues is a promising target to combat obesity and its related disorders in human beings. This goal has been especially encouraged by new important discoveries of human brown adipose tissues. The accumulating evidence confirms the presence of active brown adipocytes, not only in newborns, but also in adult humans. In rodents, there are two populations of the Ucp1-expressing adipocytes with well characterized-thermogenic functions, classical interscapular brown adipocytes and brite/beige adipocytes (brown adipocytes that are induced in white adipose tissues). Importantly, the anatomical localization, gene expression profiling and functional characterization of Ucp1-expressing fat cells indicates brite and brown adipocytes coexist in human beings. Therefore, the research directions of brown and brite adipogenesis provide lead to potential new therapies to fight obesity and its related metabolic diseases in human being. The objectives of this review are (1) to discuss the fate of primary adipocytes based on tissue origins, and (2) to discuss mechanisms of brown and brite adipogenesis which could lead to their different responses to browning reagents.



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Glycogen synthase from the parabasalian parasite Trichomonas vaginalis: An unusual member of the starch/glycogen synthase family

Publication date: Available online 30 April 2017
Source:Biochimie
Author(s): Wayne A. Wilson, Prajakta Pradhan, Nayasha Madhan, Galen C. Gist, Andrew Brittingham
Trichomonas vaginalis, a parasitic protist, is the causative agent of the common sexually-transmitted infection trichomoniasis. The organism has long been known to synthesize substantial glycogen as a storage polysaccharide, presumably mobilizing this compound during periods of carbohydrate limitation, such as might be encountered during transmission between hosts. However, little is known regarding the enzymes of glycogen metabolism in T. vaginalis. We had previously described the identification and characterization of two forms of glycogen phosphorylase in the organism. Here, we measure UDP-glucose-dependent glycogen synthase activity in cell-free extracts of T. vaginalis. We then demonstrate that the TVAG_258220 open reading frame encodes a glycosyltransferase that is presumably responsible for this synthetic activity. We show that expression of TVAG_258220 in a yeast strain lacking endogenous glycogen synthase activity is sufficient to restore glycogen accumulation. Furthermore, when TVAG_258220 is expressed in bacteria, the resulting recombinant protein has glycogen synthase activity in vitro, transferring glucose from either UDP-glucose or ADP-glucose to glycogen and using both substrates with similar affinity. This protein is also able to transfer glucose from UDP-glucose or ADP-glucose to maltose and longer oligomers of glucose but not to glucose itself. However, with these substrates, there is no evidence of processivity and sugar transfer is limited to between one and three glucose residues. Taken together with our earlier work on glycogen phosphorylase, we are now well positioned to define both how T. vaginalis synthesizes and utilizes glycogen, and how these processes are regulated.



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Response: Amiodarone-induced thyroid dysfunction and a perturbed N-desethyl-amiodarone to amiodarone ratio; could a drug-induced toxicity be regulating exposure to the offending agent?

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A systematic review of interventions to deprescribe benzodiazepines and other hypnotics among older people

Abstract

Purpose

Benzodiazepines are effective medicines for insomnia and anxiety but are commonly used beyond recommended treatment time frames, which may lead to adverse drug events. The aim of this systematic review was to critically evaluate the success of interventions used to reduce benzodiazepines and 'Z-drug' use, and the impact of these interventions on clinical outcomes in older adults.

Methods

A search was conducted in PubMed, Embase, Informit, International Pharmaceutical Abstracts, Scopus, PsychINFO, Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL. Studies conducted in older adults (≥65 years) and published between January 1995 and July 2015 were included. Two authors independently reviewed all articles for eligibility and extracted the data.

Results

Seven studies of benzodiazepines and Z-drug withdrawal were identified. Benzodiazepine discontinuation rates were 64.3% in one study that employed pharmacological substitution with melatonin and 65.0% in a study that employed general practitioner-targeted intervention. Mixed interventions including patient education and tapering (n = 2), pharmacological substitution with psychological support (n = 1) and tapering with psychological support (n = 1) yielded discontinuation rates between 27.0 and 80.0%. Five studies measured clinical outcomes following benzodiazepine discontinuation. Most (n = 4) observed no difference in prevalence of withdrawal symptoms or sleep quality, while one study reported decline in quality of life in those who continued taking benzodiazepine vs. those who discontinued over 8 months.

Conclusions

Current evidence shows that benzodiazepine withdrawal is feasible in the older population, but withdrawal rates vary according to the type of intervention. As the benefits and sustainability of these interventions are unclear, further studies should be conducted to assess this.

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Tumores primarios del espacio parafaríngeo

Publication date: May–June 2017
Source:Acta Otorrinolaringológica Española, Volume 68, Issue 3
Author(s): Gianluigi Grilli, Vanessa Suarez, María Gabriela Muñoz, María Costales, José Luis Llorente
Introducción y objetivosEl objetivo de este estudio es presentar nuestra experiencia en el diagnóstico y tratamiento de los tumores parafaríngeos.Pacientes y métodoRealizamos un estudio retrospectivo de 90 pacientes, diagnosticados y tratados quirúrgicamente de una tumoración parafaríngea entre 1984 y 2015. Fueron excluidos los pacientes cuyos tumores no eran primarios, sino que invadían esta región por contigüidad, los tumores originados en el lóbulo profundo de la parótida y las metástasis de otros tumores de cabeza y cuello.ResultadosEl 74% de las neoplasias del espacio parafaríngeo fueron de naturaleza benigna y el 26% maligna. Los adenomas pleomorfos fueron los tumores más frecuentes (27%), seguido por los paragangliomas (25%), un grupo de tumores de origen misceláneo de naturaleza maligna (16%), los tumores de origen neurogénico (12%), un grupo de tumores de origen misceláneo de naturaleza benigna (10%) y los tumores malignos de glándulas salivales (10%). El tratamiento fue quirúrgico en todos los casos. Se realizó un abordaje transcervical en 56 pacientes, un abordaje cervical-transparotídeo en 15 pacientes, un abordaje infratemporal tipo A en 13 pacientes, un abordaje transmandibular en 4 pacientes y en 2 casos un abordaje transoral. Las complicaciones más frecuentes fueron las derivadas de lesiones de estructuras nerviosas.ConclusionesLa mayoría de los tumores localizados en el espacio parafaríngeo son subsidiarios de ser tratados de forma quirúrgica con una baja tasa de complicaciones y recurrencias. El abordaje transcervical es el más utilizado.Introduction and objectivesThe aim of this study is to present our experience with the diagnostic and therapeutic approaches for parapharyngeal space tumours.Patients and methodThis study is a retrospective review of 90 patients diagnosed with tumours of the parapharyngeal space and treated surgically between 1984 and 2015. Patients whose tumours were not primary but invaded the parapharyngeal space expanding from another region, tumours originating in the deep lobe of the parotid gland and head and neck metastasis were excluded from this study.Results74% percent of the parapharyngeal space neoplasms were benign and 26% were malignant. Pleomorphic adenoma was the most common neoplasm (27%), followed by paragangliomas (25%), miscellaneous malignant tumours (16%), neurogenic tumours (12%), miscellaneous benign tumours (10%), and malignant salivary gland tumours (10%). The transcervical approach was used in 56 cases, cervical-transparotid approach in 15 cases, type A infratemporal fossa approach in 13 cases, transmandibular approach in 4 cases and transoral approach in 2 cases. The most common complications were those deriving from nervous injuries.ConclusionsMost parapharyngeal space tumours can be removed surgically with a low rate of complications and recurrence. The transcervical approach is the most frequently used.



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Lateral Flow Assays for the Diagnosis of Invasive Aspergillosis: Current Status

Abstract

Purpose of Review

Diagnosis during early stages of invasive aspergillosis (IA) and targeted antifungal treatment has the potential to improve survival significantly. Despite advances in the diagnostic arsenal, invasive mold infections remain difficult to diagnose—especially at early stages before typical radiological signs develop. Varying availability and time-to-results are important limitations of current approved biomarkers and molecular assays for diagnosis of IA. Here, we will give an update on the Aspergillus-specific lateral-flow device (LFD) test. We further review promising findings on feasibility of point-of-care (POC) detection of urinary excreted fungal galactomannan-like antigens.

Recent Findings

POC LFD assays for detection of Aspergillus antigens are currently in development. The Aspergillus-specific LFD test, which is based on the JF5 antibody (Ab), detects an extracellular glycoprotein antigen secreted during active growth of Aspergillus spp. The test has shown promising results in various studies. In addition, a monoclonal Ab476-based LFD for POC detection of urinary excreted fungal galactomannan-like antigens has been developed but needs further validation.

Summary

Important advances have been made in the development of LFD assays for IA. Most promising is the Aspergillus-specific LFD test; commercial availability is still pending, however. The search for reliable POC tests for other molds, including mucorales, continues.

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MALDI-TOF MS and Filamentous Fungal Identification: A Success Story?

Abstract

Purpose of Review

The diagnosis of invasive fungal disease remains challenging in the clinical laboratory. In this paper, the use of matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) for the identification of filamentous fungi as well as its application for antifungal resistance testing and strain typing is evaluated.

Recent Findings

Most studies report very high accuracy for the identification of filamentous fungi by MALDI-TOF MS. Its cost effectiveness, short analysis time, and low error rate and the fact that it can also discriminate between closely related and cryptic species make it appropriate for implementation in the clinical routine. Two drawbacks remain in the availability of extended reference spectra databases and the fact that this technique can only be applied on isolates.

Summary

More work on (simultaneous) antifungal susceptibility testing and strain typing is needed. The application of MALDI-TOF MS directly on clinical specimens would further improve the diagnosis of invasive fungal disease and improve its successful management.

http://ift.tt/2pv3Wet