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Transcriptome profiling reveals the immune response of goose T cells under selenium stimuli.

Anim Sci J. 2017 Dec;88(12):2001-2009

Authors: Cao N, Li W, Li B, Tian Y, Xu D

Abstract
The goose is an economically important poultry species and a principal natural host of avian viruses. This study aimed to determine the effects of selenium on the immune response of geese. Under selenium stimulation, gene expression profiling was investigated using transcriptome sequencing. The selenoproteins were promoted by selenium stimulation, while the heat shock proteins, interleukin and interferons were mainly down-regulated. After comparison, 2228 differentially expressed genes were primarily involved in immune and environmental response, and infectious disease and genetic information processing related pathways were identified. Specifically, the enzymes of the lysosomes which acted as a safeguard in preventing pathogens were mostly up-regulated and six randomly selected differentially expressed genes were validated by quantitative polymerase chain reaction. In addition, the most proportional increased transcription factor family basic helix-loop-helix (bHLH) located in the 5' flank of selenoprotein P-like protein for selenium metabolism was identified by response to the selenium stimulation in this study. These analyses show that selenium can promote immune function by activating selenoproteins, transcript factors and lysosome pathway related genes, while weakening cytokine content genes in geese.

PMID: 28749043 [PubMed - indexed for MEDLINE]

Drug-Induced Photosensitivity - a Continuing Diagnostic Challenge.

Acta Clin Croat. 2017 Jun;56(2):277-283

Authors: Lugović-Mihić L, Duvančić T, Ferček I, Vuković P, Japundžić I, Ćesić D

Abstract
When taking different drugs, their possible side effects on the skin should be considered, including skin reactions connected to photosensitivity. This photosensitivity caused by drugs can appear as phototoxic reactions (which occur more often) or photoallergic reactions (which occur less often and include allergic mechanisms). The following drugs stand out as medications with a high photosensitivity potential: nonsteroidal anti-inflammatory drugs (NSAIDs), cardiovascular drugs (such as amiodarone), phenothiazines (especially chlorpromazine), retinoids, antibiotics (sulfonamides, tetracyclines, especially demeclocycline and quinolones), etc. In recent years, photosensitive reactions to newer drugs have appeared, e.g., targeted anticancer therapies such as BRAF kinase inhibitors (vemurafenib, dabrafenib), EGFR inhibitors, VEGFR inhibitors, MEK inhibitors, Bcr-Abl tyrosine kinase inhibitors, etc. In patients taking drugs over a longer period of time (e.g., NSAIDs, cardiovascular drugs, etc.), a particular problem arises when an unrecognized drug-induced photosensitivity on the skin manifests in summer months. When taking patient histories, the physician/dermatovenereologist should bear in mind that any drug the patient is currently taking may be the cause of skin reactions. Therefore, patients who use potentially photosensitive drugs and treatments on a long term basis should be warned of the possibility of these side effects on their skin and advised to avoid direct exposure to sunlight and to use adequate photoprotection. If patients carefully protect themselves from the sun, it is often not necessary to stop treatments that include photosensitive drugs. If such reactions appear, anti-inflammatory and antiallergic therapies should be introduced.

PMID: 29485795 [PubMed - in process]

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Treatment of Tardive Dyskinesia: A General Overview with Focus on the Vesicular Monoamine Transporter 2 Inhibitors.

Drugs. 2018 Feb 26;:

Authors: Niemann N, Jankovic J

Abstract
Tardive dyskinesia (TD) encompasses the spectrum of iatrogenic hyperkinetic movement disorders following exposure to dopamine receptor-blocking agents (DRBAs). Despite the advent of atypical or second- and third-generation antipsychotics with a presumably lower risk of complications, TD remains a persistent and challenging problem. Prevention is the first step in mitigating the risk of TD, but early recognition, gradual withdrawal of offending medications, and appropriate treatment are also critical. As TD is often a persistent and troublesome disorder, specific antidyskinetic therapies are often needed for symptomatic relief. The vesicular monoamine transporter 2 (VMAT2) inhibitors, which include tetrabenazine, deutetrabenazine, and valbenazine, are considered the treatment of choice for most patients with TD. Deutetrabenazine-a deuterated version of tetrabenazine-and valbenazine, the purified parent product of one of the main tetrabenazine metabolites, are novel VMAT2 inhibitors and the only drugs to receive approval from the US FDA for the treatment of TD. VMAT2 inhibitors deplete presynaptic dopamine and reduce involuntary movements in many hyperkinetic movement disorders, particularly TD, Huntington disease, and Tourette syndrome. The active metabolites of the VMAT2 inhibitors have high affinity for VMAT2 and minimal off-target binding. Compared with tetrabenazine, deutetrabenazine and valbenazine have pharmacokinetic advantages that translate into less frequent dosing and better tolerability. However, no head-to-head studies have compared the various VMAT2 inhibitors. One of the major advantages of VMAT2 inhibitors over DRBAs, which are still being used by some clinicians in the treatment of some hyperkinetic disorders, including TD, is that they are not associated with the development of TD. We also briefly discuss other treatment options for TD, including amantadine, clonazepam, Gingko biloba, zolpidem, botulinum toxin, and deep brain stimulation. Treatment of TD and other drug-induced movement disorders must be individualized and based on the severity, phenomenology, potential side effects, and other factors discussed in this review.

PMID: 29484607 [PubMed - as supplied by publisher]

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Retrospective evaluation of concomitant cetuximab and radiotherapy tolerance for locoregional advanced head and neck squamous cell carcinoma treatment in patients unfit for platinum-based chemotherapy.

Eur Arch Otorhinolaryngol. 2017 Jul;274(7):2883-2889

Authors: Rambeau A, Gervais R, De Raucourt D, Babin E, Dugué AE, Florescu C, Blanchard D, Gery B

Abstract
Radiotherapy associated with cetuximab (Cet-RT) is an alternative treatment to platinum-based chemoradiotherapy in locally advanced head and neck carcinoma (LAHNC). Reviews suggest that the use of cetuximab is associated with poorer tolerance in patients unfit for chemotherapy than in pivotal trial. We retrospectively studied patients first treated by Cet-RT for LAHNC presenting contraindications to chemoradiotherapy. Objectives were treated population description, acute tolerance, progression-free survival (PFS), overall survival (OS), and 3-month clinical response. Eighty-eight patients were included. Treatment was completed without delay for 43 patients. Grade 3-4 acute toxicity was described in 44.3%: mucositis (n = 20), radiodermatitis (n = 25) folliculitis (n = 10), and anaphylaxis (n = 6). Fourteen patients died during treatment. Median PFS and OS were 6.3 and 18.7 months, respectively. We confirm that Cet-RT tolerance in unfit patients is poorer than that in trials. Survival data illustrate patients' frailty and suggest that balanced use of Cet-RT is required in this population.

PMID: 28382396 [PubMed - indexed for MEDLINE]

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Long-term outcome and safety of prolonged bedaquiline treatment for multidrug-resistant tuberculosis.

Eur Respir J. 2017 Mar;49(3):

Authors: Guglielmetti L, Jaspard M, Le Dû D, Lachâtre M, Marigot-Outtandy D, Bernard C, Veziris N, Robert J, Yazdanpanah Y, Caumes E, Fréchet-Jachym M, French MDR-TB Management Group

Abstract
Bedaquiline, a recently approved drug for the treatment of multidrug-resistant tuberculosis (MDR-TB), is recommended for a duration of 24 weeks. There are scarce data on patients treated with this drug outside clinical trials.All MDR-TB patients who started treatment from January 1, 2011 to December 31, 2013 and received ≥30 days of bedaquiline were included in a multicentre observational cohort.Among 45 MDR-TB patients, 53% harboured isolates resistant to both fluoroquinolones and second-line injectables, and 38% harboured isolates resistant to one of these drug classes. Median bedaquiline treatment duration was 361 days and 33 patients (73%) received prolonged (>190 days) bedaquiline treatment. Overall, 36 patients (80%) had favourable outcome, five were lost to follow-up, three died, and one failed and acquired bedaquiline resistance. No cases of recurrence were reported. Severe and serious adverse events were recorded in 60% and 18% of patients, respectively. Values of Fridericia-corrected QT interval (QTcF) >500 ms were recorded in 11% of patients, but neither arrhythmias nor symptomatic cardiac side-effects occurred. Bedaquiline was discontinued in three patients following QTcF prolongation. No significant differences in outcomes or adverse events rates were observed between patients receiving standard and prolonged bedaquiline treatment.Bedaquiline-containing regimens achieved favourable outcomes in a large proportion of patients. Prolonged bedaquiline treatment was overall well tolerated in this cohort.

PMID: 28182570 [PubMed - indexed for MEDLINE]

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Can drugs induce or aggravate sleep apneas? A case-noncase study in VigiBase® , the WHO pharmacovigilance database.

Fundam Clin Pharmacol. 2017 Jun;31(3):359-366

Authors: Linselle M, Sommet A, Bondon-Guitton E, Moulis F, Durrieu G, Benevent J, Rousseau V, Chebane L, Bagheri H, Montastruc F, Montastruc JL

Abstract
The potential favorizing role of drugs in sleep apnea syndrome (SAS) is unknown. This study investigates drugs associated with SAS in a pharmacovigilance database. SAS recorded as adverse drug reactions (ADRs) in VigiBase® , the WHO pharmacovigilance database (more than 11 million reports), from 1978 to 2015 was selected. The risk of SAS reports was estimated using the case-noncase method, with cases being SAS and noncases all other recorded ADRs. During this 37-year period, 3325 ADRs including the word SAS were registered (0.05% of the database). Mean age was 51.2 ± 16.9 years with 52% men. ADRs were 'serious' in around 82% of cases. The case-noncase study found an association between SAS and exposition with sodium oxybate, rofecoxib, quetiapine, and clozapine for individual drugs and coxibs, antipsychotics, benzodiazepines, and opium alkaloids for drug classes. The potential role of other drugs is discussed. This study suggests that SAS can be associated with some drugs (mainly psychotropics) that are able to reveal or aggravate such a disease. Physicians should take into account the role of drugs in the etiological appraisal and management of SAS.

PMID: 28036099 [PubMed - indexed for MEDLINE]

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Funding Opportunity PAR-18-683 from the NIH Guide for Grants and Contracts. The objective of this funding opportunity is to support investigator-initiated, phase I clinical trials for diagnostic and therapeutic interventions for heart, lung, blood, and sleep (HLBS) disorders in adults and children. The proposed trial can be single or multisite. Applications submitted to this FOA must be relevant to the research mission of the NHLBI and meet the NIH definition of a clinical trial (see NOT-OD-15-015). For additional information about the mission, strategic vision, and research priorities of the NHLBI, applicants are encouraged to consult the NHLBI website: http://www.nhlbi.nih.gov. This FOA will utilize a bi-phasic, milestone-driven mechanism of award where the first phase can be used to finalize required pre-trial activities such as stability, shipping studies, and site training. It is anticipated that applications will present the scientific rationale for the clinical trial and a comprehensive scientific and operational plan that describes the plans for project management, subject recruitment and retention, performance milestones, scientific conduct of the trial, and dissemination of results. The multiple PD/PI model is strongly encouraged but not required. Applicants are encouraged to form a team with expertise in biostatistics, clinical trial design, and coordination as well as product manufacturing and formulation as appropriate. Applicants are strongly encouraged to contact the appropriate Scientific/Research contact prior to submitting an application due to the complex nature of conducting a clinical trial. Staff will be able to assist applicants in meeting the objectives of this FOA.

Funding Opportunity PAR-18-684 from the NIH Guide for Grants and Contracts. The objective of this funding opportunity is to support investigator-initiated, phase I clinical trials for diagnostic and therapeutic interventions for heart, lung, blood, and sleep (HLBS) disorders in adults and children. The proposed trial can be single or multisite. Applications submitted to this FOA must be relevant to the research mission of the NHLBI and meet the NIH definition of a clinical trial (see NOT-OD-15-015). For additional information about the mission, strategic vision, and research priorities of the NHLBI, applicants are encouraged to consult the NHLBI website: http://www.nhlbi.nih.gov. This FOA will utilize a bi-phasic, milestone-driven mechanism of award where the first phase can be used to finalize required pre-trial activities such as stability, shipping studies, and site training. It is anticipated that applications will present the scientific rationale for the clinical trial and a comprehensive scientific and operational plan that describes the plans for project management, subject recruitment and retention, performance milestones, scientific conduct of the trial, and dissemination of results. The multiple PD/PI model is strongly encouraged but not required. Applicants are encouraged to form a team with expertise in biostatistics, clinical trial design, and coordination as well as product manufacturing and formulation as appropriate. Applicants are strongly encouraged to contact the appropriate Scientific/Research contact prior to submitting an application due to the complex nature of conducting a clinical trial. Staff will be able to assist applicants in meeting the objectives of this FOA.

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