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Fern-7-en-19 alpha-ol

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PMID

12236842

Abstract

The established place of regular long-acting β2-adrenoceptor agonists at step 3 in asthma management guidelines has evolved as a consequence of evidence showing additive effects of salmeterol and formoterol on exacerbation rates, resulting in a putative inhaled corticosteroid sparing effect. There is however, evidence to show that although long-acting β2-adrenoceptor agonists facilitate using a lower dose of inhaled corticosteroid, this may occur at the expense of suboptimal anti-inflammatory control. This is likely to be the case especially with fixed dose combination inhalers where it is not possible to properly titrate anti-inflammatory therapy with inhaled corticosteroids without also inadvertently overtreating with unnecessarily high doses of long-acting β2-adrenoceptor agonists. Most patients with mild to moderate persistent asthma can be adequately controlled on monotherapy with inhaled corticosteroid in low or medium dosage, which is considerably cheaper than concomitant use of a long-acting β2-adrenoceptor agonist. Subsensitivity to long-acting β2-adrenoceptor agonists is a predictable pharmacological phenomenon which occurs despite concomitant inhaled corticosteroid therapy and occurs more readily for bronchoprotective than bronchodilator effects. Subsensitivity of salbutamol protection against bronchoconstrictor stimuli occurs in patients receiving concomitant long-acting β2-adrenoceptor agonists, which may be due to β2-adrenoceptor down-regulation or prolonged receptor occupancy. Prospective large scale long-term studies are required to further define the clinical relevance of β2-adrenoceptor polymorphisms, to look at clinical control outcomes as well as propensity for subsensitivity. It would therefore make more sense to first of all optimize the dose of anti-inflammatory therapy with inhaled corticosteroid and to then consider adding a long-acting β2-adrenoceptor agonist for patients who are poorly controlled.

KEYWORDS

asthma, β2-adrenoceptor agonists, formoterol, salmeterol, subsensitivity

Title

Antagonism of long-acting β2-adrenoceptor agonism

Author

Brian J Lipworth

Publish date

2002 Sep;

PMID

29196295

Abstract

Metagenomics analysis of food samples promises isolation-independent detection and subtyping of foodborne bacterial pathogens in a single workflow. The selective concentration of Salmonella genomic DNA by immunomagnetic separation (IMS) and multiple displacement amplification (MDA) shortened the time for culture enrichment of Salmonella-spiked raw chicken breast samples by over 12 h while permitting serotyping and high-fidelity single nucleotide polymorphism (SNP) typing of the pathogen using short shotgun sequencing reads. The herein-termed quasimetagenomics approach was evaluated on Salmonella-spiked lettuce and black peppercorn samples as well as retail chicken parts naturally contaminated with different serotypes of Salmonella. Culture enrichment of between 8 and 24 h was required for detecting and subtyping naturally occurring Salmonella from unspiked chicken parts compared with 4- to 12-h culture enrichment when Salmonella-spiked food samples were analyzed, indicating the likely need for longer culture enrichment to revive low levels of stressed or injured Salmonella cells in food. A further acceleration of the workflow was achieved by real-time nanopore sequencing. After 1.5 h of analysis on a potable sequencer, sufficient data were generated from sequencing the IMS-MDA products of a cultured-enriched lettuce sample to enable serotyping and robust phylogenetic placement of the inoculated isolate.

IMPORTANCE Both culture enrichment and next-generation sequencing remain time-consuming processes for food testing, whereas rapid methods for pathogen detection are widely available. Our study demonstrated a substantial acceleration of these processes by the use of immunomagnetic separation (IMS) with multiple displacement amplification (MDA) and real-time nanopore sequencing. In one example, the combined use of the two methods delivered a less than 24-h turnaround time from the collection of a Salmonella-contaminated lettuce sample to the phylogenetic identification of the pathogen. An improved efficiency such as this is important for further expanding the use of whole-genome and metagenomics sequencing in the microbial analysis of food. Our results suggest the potential of the quasimetagenomics approach in areas where rapid detection and subtyping of foodborne pathogens are important, such as for foodborne outbreak response and the precision tracking and monitoring of foodborne pathogens in production environments and supply chains.

KEYWORDS

Salmonella, detection, subtyping, metagenomics, MinION

Title

Quasimetagenomics-Based and Real-Time-Sequencing-Aided Detection and Subtyping of Salmonella enterica from Food Samples

Author

Ji-Yeon Hyeon,#a Shaoting Li,#a David A. Mann,a Shaokang Zhang,a Zhen Li,b Yi Chen,c and Xiangyu Dengcorresponding authora

Publish date

2018 Feb 15;

PMID

27799957

Abstract

Background
Cow’s milk allergy is one of the most common food allergies affecting young children. A subset of milk-allergic individuals can eat baked milk without allergic symptoms which is beneficial in terms of prognostication and liberalization of the diet. A retrospective study suggested that skin prick testing (SPT) with a baked milk (muffin) slurry may provide a sensitive means of predicting the outcome of a medically supervised baked milk oral food challenge. We evaluated the predictive value of SPT with baked milk to identify unheated milk-allergic children who are able to safely eat baked milk.

Methods
Children aged 2-16 years with a prior history of reaction to milk and a milk extract SPT of 8-14 mm were recruited. Investigator-blinded SPT to muffin slurry and powdered milk in triplicate and specific IgE (sIgE) to casein and milk were performed. Graded oral challenge to egg-free baked milk muffins (total 2.6 gm milk protein) was performed in the hospital. Reliability of tests was analyzed for intraclass correlation. Statistical significance for clinical characteristics of population and muffin testing versus baked milk reactivity was calculated with Fisher exact test for dichotomous and t-test for continuous variables. Wilcoxon rank sum test was used to compare immunological characteristics between individuals who tolerated or reacted to baked milk. Fitted predicted probability curves and ROC curves were generated.

Results
Thirty-eight children were consented and 30 met study criteria. The muffin SPT and casein sIgE were significantly different in those who passed versus failed baked milk challenge. Negative (<3 mm) baked milk tests were found in 8/30 children (27 %) and were associated with non-reactivity to baked milk (p = 0.01) with a sensitivity of 1 (0.70-1.00). All children with negative SPT for baked milk passed the oral challenge. Specificity was 0.41 (0.19-0.67). The optimal decision point for the muffin SPT was 4 mm and the casein sIgE was 6 kU/L. The powdered milk test was not helpful. Conclusions Skin prick testing with a baked milk (muffin) slurry may have a role in clinical practice to identify baked milk tolerance in milk-allergic patients.

KEYWORDS

Cow’s milk allergy, Baked milk, Skin prick testing

Title

Prospective evaluation of testing with baked milk to predict safe ingestion of baked milk in unheated milk-allergic children

Author

Allison Kwan,1,2 Maria Asper,1,2 Sasson Lavi,1,2 Elana Lavine,3,4 David Hummel,1,2 and Julia E. Uptoncorresponding author1,2

Publish date

2016;