Poisoning due to ingestion of foods with elevated levels of biogenic amines (histamine, putrescine, cadaverine, and tyramine) is well documented. Histamine fish poisoning largely is due to growth of ...naturally occurring bacteria associated with scombroid fish species. A rapid and reliable method is needed to screen for the presence of histamine-forming bacteria in fish. This study included a comparison of three methods for the detection of histamine-producing bacteria. A total of 152 histamine-producing and non-histamine-producing bacteria from multiple sources were screened using a modified Niven's agar method, a potentiometric method, and a PCR-based assay targeting a 709-bp fragment of the histidine decarboxylase gene. Histamine production by bacterial isolates was confirmed by high-performance liquid chromatography (HPLC). Bacterial strains were categorized as producing high amounts of histamine, low amounts of histamine, or no histamine. Of the 152 strains tested, 128 (84%) were positive with the Niven's agar method, 73 (48%) were positive with the potentiometric technique, and 74 (49%) were positive with the PCR assay. Overall, a 38% false-positive rate was observed with the modified Niven's agar method, although this method detected both low-histamine and high-histamine strains. There was a high degree of concordance (>99%) between results of the potentiometric and PCR methods, but neither of these methods detected low-histamine bacteria. These observations support the need for a simple and straightforward yet sensitive method for detecting histamine-producing bacteria in seafood and environmental samples.
The article discusses the confusion pertaining to the use and interpretation of race, ethnicity, and ancestry data in biomedical research. The need is to understand that imprecise use of race and ...ethnicity data as population descriptors has the potential to miscommunicate the complex relationships among an individual's social identity, ancestry, socioeconomic status, and health, while also perpetuating misguided notions that discrete genetic groups exist. The challenge that scientists and medical journal editors must address is how to report human genomic variation without inappropriately describing racial and ethnic groups as discrete population groups.
The solubilities of ethane and ethylene in the lipidic ionic liquid 1-(Z-octadec-9-enyl)-3-methylimidazolium bistriflimide are measured at 298, 313, and 333 K from 0.1 MPa to about 2 MPa and are ...correlated and well reproduced with the Krichevsky-Kasarnovsky equation. Ethane is shown to have slightly higher solubility than ethylene, in agreement with results from other ionic liquids with significant nonpolar structural content, although fit Henry’s constants are the same within experimental error. Additionally, this is the first example of an imidazolium-based ionic liquid with Henry’s constants for ethane and ethylene that are below 5 MPa at room temperature. This supports the idea that these classes of solvents have “nonpolar-like” solvent properties and may be used as alternatives for reaction and separations processes that currently require volatile, nonpolar solvents, even though these species are ionic in nature. Experimental solubility data are compared to COSMO-RS predictions, which give good qualitative predictions of solubility but significantly overpredict the Henry’s constant for both species.
Recent spectacular advances in the technologies and strategies for DNA sequencing have profoundly accelerated the detailed analysis of genomes from myriad organisms. The past few years alone have ...seen the publication of near-complete or draft versions of the genome sequence of several well-studied, multicellular organisms - most notably, the human. As well as providing data of fundamental biological significance, these landmark accomplishments have yielded important strategic insights that are guiding current and future genome-sequencing projects.
Drug Metabolites in Safety Testing Baillie, Thomas A.; Cayen, Mitchell N.; Fouda, Hassan ...
Toxicology and applied pharmacology,
08/2002, Volume:
182, Issue:
3
Journal Article
Peer reviewed
This report summarizes the deliberations of a multidisciplinary committee, sponsored by the Pharmaceutical Research and Manufacturers of America, on current “best practices” within the U.S. ...pharmaceutical industry in assessing the role of drug metabolites as potential mediators of the toxicity of new drug products. Input to the document was obtained from numerous sources, including members of the pharmaceutical industry, academic investigators, and representatives of regulatory agencies who attended a workshop on the subject in November 2000. The overall goal of the paper is to define practical and scientifically based approaches to the use of metabolite data that address contemporary issues in the safety evaluation of drug candidates. Although there remains a lack of consensus on how best to deal with several aspects of this complex subject, this paper raises a number of points to consider, which emphasize the need to treat drug metabolite issues on a case-by-case basis. It is hoped that the discussion will promote continued dialog among industrial scientists and regulators charged with ensuring the clinical safety of new therapeutic agents.
Protein phosphorylation plays a critical role in a variety of cellular functions. As a result, the monitoring of phosphoproteins in cells represents an important goal for proteomics research. To ...facilitate phosphoprotein detection, the first enzymatic phosphorylation-dependent biotinylation reaction of proteins is described. Specifically, kinase enzymes were coupled with an ATP-biotin conjugate to efficiently biotinylate substrate peptides and proteins after phosphate transfer. The kinase-mediated biotinylation reaction enables efficient detection of phosphoproteins in cell lysates or phosphopeptides after trypsin proteolysis, demonstrating its utility for proteomics research. Importantly, the studies reveal the cosubstrate promiscuity of kinase enzymes, laying the foundation for development of new chemical tools targeting the phosphoproteome.
•Population prevalence of gestational hypercalcemia was 1.7 % in the third trimester.•Hyperparathyroidism and vitamin D toxicity were excluded as main causes.•No cases with profiles suggestive of ...mutations in the CYP24A1 gene were found.•Hypercalcemic women had a relatively high serum 1,25(OH)2D concentration despite an appropriately suppressed PTH.
Gestational hypercalcemia is associated with an increased risk of maternal, fetal and neonatal morbidity and mortality. Hypercalcemia may develop during pregnancy in individuals who were previously asymptomatic. The increased sensitivity during pregnancy may be related to physiological, gestational alterations in vitamin D and calcium metabolism and may be influenced by gene variants. The prevalence is unknown.
We investigated the prevalence of hypercalcemia in trimester 3 (T3) in a population representative prospective cohort study (n = 1832) in South-West Sweden. Women with serum albumin (Alb) adjusted calcium (CaAlb) ≥ 2.65 mmol/L in T3 (n = 30) were matched to normo-calcemic controls, and markers of calcium and vitamin D metabolism were investigated in trimester 1 (T1) and T3. Serum concentrations of Ca, phosphate (P), Magnesium (Mg), Alb and creatinine (Cr), parathyroid hormone (PTH; T3 only), vitamin D metabolites (total 25(OH)D, 1,25(OH)2D, 24,25(OH)2D, and free 25(OH)D) were analysed in T1 and T3. CaAlb (Payne; inter-laboratory difference: UEA = 0.15 + 0.9*UGOT; UEA 2.54 = UGOT 2.65) and estimated glomerular filtration rate (eGFR; modified 4-variable MDRD) and vitamin D metabolites ratios (VMR) were calculated. Normally and non-normally distributed data were presented as mean (SD) or median (95 %CI). Group differences in relationships between vitamin D metabolites and with PTH were investigated with multiple regression analyses.
Hypercalcemia in T3 was found in 1.7 % of women. PTH concentrations suggestive of primary hyperparathyroidism was found in 1 woman and none had 25(OH)D or 24,25(OH)2D concentrations in the toxicity range or suggestive of mutations in the CYP24A1 gene. CaAlb was significantly higher in hypercalcemic cases compared to controls in T1 (2.44 (2.30–2.80) vs 2.37 (2.25–2.49) mmol/L) and T3 (2.63 (2.52–2.78) vs 2.46 (2.31–2.58) mmol/L). Serum P was higher among cases than controls in T3 (1.12 (0.16) vs 1.07 (0.18) mmol/L) but not in T1 (1.12 (0.18) and 1.12 (0.16) mmol/L). PTH in T3 was lower in cases (1.6 (1.6–2.8) vs 2.3 (2.1–2.8) pmol/L) but 1,25(OH)2D concentrations were similar. There were no significant group differences in serum 25(OH)D, free 25(OH)D, 24,25(OH)2D, Mg, Alb, Cr and eGFR. Regression analyses did not show significant differences between cases and controls in relationships between vitamin D metabolites and with PTH, except for the free 25(OH)D-PTH relationship and a higher free:total 25(OH)D ratio in cases at T1.
In conclusion, most common causes of hypercalcemia were excluded in the majority of women. Hypercalcemic women had a relatively high serum 1,25(OH)2D concentration despite an appropriately suppressed PTH, suggestive of abnormal gestational adaptions.
Aminoglycosides are broad-spectrum antibiotics commonly used for the treatment of serious bacterial infections. Decades of clinical use have led to the widespread emergence of bacterial resistance to ...this family of drugs limiting their efficacy in the clinic. Here, we report the development of a methodology that utilizes aminoglycoside acetyltransferases (AACs) and unnatural acyl coenzyme A analogues for the chemoenzymatic generation of N-acylated aminoglycoside analogues. Generation of N-acylated aminoglycosides is followed by a simple qualitative test to assess their potency as potential antibacterials. The studied AACs (AAC(6′)-APH(2′′) and AAC(3)-IV) show diverse substrate promiscuity towards a variety of aminoglycosides as well as acyl coenzyme A derivatives. The enzymes were also used for the sequential generation of homo- and hetero-di-N-acylated aminoglycosides. Following the clinical success of the N-acylated amikacin and arbekacin, our chemoenzymatic approach offers access to regioselectively N-acylated aminoglycosides in quantities that allow testing of the antibacterial potential of the synthetic analogues making it possible to decide which molecules will be worth synthesizing on a larger scale.
In contrast to the widespread view that the Middle Ages were a static, unchanging period in which attitudes to women were uniformly negative, D. H. Green argues that around 1200 the conventional ...relationship between men and women was subject to significant challenge through discussions in the vernacular literature of the period. Hitherto scholarly interest in gender relations in such literature has largely focused on French romance or on literature in English from a later period. By turning the focus on the rich material to be garnered from Germany - the romances Erec, Tristan and Parzival - Professor Green shows how some vernacular writers devised methods to debate and challenge the undoubted antifeminism of the day by presenting a Utopian model, supported by a revision of views by the Church, to contrast with contemporary practice.
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