Background Tobacco smoke is a major risk factor in the development of COPD. Secondhand smoke (SHS) exposure is a known risk factor in asthma, bronchitis, and coronary artery disease. Elastin is a ...recognized target for injury in COPD, and the amino acids desmosine and isodesmosine (D/I), which are specific for elastin degradation, are elevated in COPD. This study determined whether exposure to SHS affects elastin degradation in asymptomatic individuals. Methods Two cohorts of asymptomatic individuals without evidence of respiratory or circulatory disease, exposed to SHS, were studied. Both cohorts comprised normal nonsmokers, active smokers, and those exposed to SHS. D/I were measured in plasma and quantified by high-performance liquid chromatography and tandem mass spectrometry by published methods. Plasma cotinine, a metabolite of nicotine, was also measured. Results In each cohort, the levels of D/I in plasma were statistically significantly higher in secondhand-smoke-exposed subjects than in the normal nonexposed subjects. Smokers had the highest levels of D/I but their levels were not statistically significantly higher than those of the secondhand-smoke-exposed. Cotinine levels were elevated in secondhand-smoke-exposed subjects and active smokers but not in most nonsmoking control subjects. Conclusions Results indicate a tissue matrix effect of degradation of body elastin from SHS exposure and possible lung structure injury, which may result in COPD. Long-term studies of individuals exposed to SHS for the development of COPD are warranted.
Thyroid Hormones and Methylmercury Toxicity Soldin, Offie P.; O’Mara, Daniel M.; Aschner, Michael
Biological trace element research,
12/2008, Volume:
126, Issue:
1-3
Journal Article
Peer reviewed
Open access
Thyroid hormones are essential for cellular metabolism, growth, and development. In particular, an adequate supply of thyroid hormones is critical for fetal neurodevelopment. Thyroid hormone tissue ...activation and inactivation in brain, liver, and other tissues is controlled by the deiodinases through the removal of iodine atoms. Selenium, an essential element critical for deiodinase activity, is sensitive to mercury and, therefore, when its availability is reduced, brain development might be altered. This review addresses the possibility that high exposures to the organometal, methylmercury (MeHg), may perturb neurodevelopmental processes by selectively affecting thyroid hormone homeostasis and function.
Cet article examine la mise en scène du désir lesbien dans le contexte de la ville de Paris dans A la recherche du temps perdu de Marcel Proust et Nightwood ou Le Bois de la nuit de Djuna Bornes. Ces ...deux auteurs représentent une tendance chez des femmes saphiques à vouloir explorer la capitale française à l'abri des regards épieurs, une tendance qui se transforme vite dans une envie de fuir la vie urbaine pour s'échapper au contrôle patriarcal. A travers l'analyse du vagabondage de personnages tels qu'Odette, Albertine, et Robin Vote, nous étudions la possibilité de penser l'existence des flâneuses lesbiennes ainsi que les procédés chez ces écrivains pour dépeindre la femme lesbienne à la recherche d'un chez soi convenable.
Alkaptonuria is an autosomal recessive disorder caused by pathogenic variants in the HGD gene. Deficiency of the HGD enzyme leads to tissue deposition of homogentisic acid (HGA), causing severe ...osteoarthropathies and cardiac valve degeneration. Although HGD is vital for the catabolism of tyrosine, which provides the basis for thyroid hormone synthesis, the prevalence of thyroid dysfunction in alkaptonuria is unknown.
To assess thyroid structure and function in patients with alkaptonuria.
A single-center cohort study was conducted in a tertiary referral center including patients with alkaptonuria followed up for a median of 93 (interquartile range, 48-150) months between February 1, 2000, and December 31, 2018. The alkaptonuria diagnosis was based on clinical presentation and elevated urine HGA levels. A total of 130 patients were considered for participation.
Prevalence of thyroid dysfunction in adults with alkaptonuria compared with the general population. Thyrotropin and free thyroxine levels were measured by immunoassay and repeated in each patient a median of 3 (interquartile range, 2-22) times. Neck ultrasonographic scans were analyzed in a subset of participants. Logistic regression was used to test the association of thyroid dysfunction with age, sex, thyroid peroxidase (TPO) antibodies, serum tyrosine levels, and urine HGA levels.
Of the 130 patients, 5 were excluded owing to thyroidectomy as the cause of hypothyroidism. The study cohort consisted of 125 patients; the median age was 45 (interquartile range, 35-51) years. Most of the patients were men (72 57.6%). The prevalence of primary hyperthyroidism was 0.8% (1 of 125 patients), similar to 0.5% observed in the general population (difference, 0.003; 95% CI, -0.001 to 0.04; P = .88). The prevalence of primary hypothyroidism was 16.0% (20 of 125 patients), which is significantly higher than 3.7% reported in the general population (difference, 0.12; 95% CI, 0.10-0.24; P < .001). Women were more likely to have primary hypothyroidism than men (odds ratio, 10.99; 95% CI, 3.13-38.66; P < .001). Patients with TPO antibodies had a higher likelihood of primary hypothyroidism than those without TPO antibodies (odds ratio, 7.36; 95% CI, 1.89-28.62; P = .004). There was no significant difference in the prevalence of thyroid nodules between patients in this study (29 of 49 59.2%) vs the general population (68%) (difference, 0.088; 95% CI, -0.44 to 0.73; P = .20) or of cancer (7% vs 5%; difference, 0.01; 95% CI, -0.01 to 0.17; P = .86).
The high prevalence of primary hypothyroidism noted in patients with alkaptonuria in this study suggests that serial screening in this population should be considered and prioritized.
Tandem mass spectrometry (MS/MS) is being increasingly used to identify and measure acylcarnitines in blood and urine of children suspected of having fatty oxidation disorders and other inborn errors ...of metabolism. Rapid MS/MS analysis requires simple and efficient sample preparation. We developed a LC-MS/MS method for the online extraction of acylcarnitines in plasma without derivatization that requires only precipitation of proteins by acetonitrile followed by centrifugation, thus increasing efficiency.
An API-3000 tandem mass spectrometer (SCIEX, Toronto, Canada) equipped with electrospray ionization (ESI), TurboIon Spray source, three Shimadzu LC10AD micropumps and autosampler (Shimadzu Scientific Instruments, Columbia, MD) was used to perform the analysis. Within-day and between-day imprecision was evaluated for 10 analytes in the MRM mode using 3 levels of controls. Accuracy was determined by comparing the method with another MS/MS procedure and by recovery experiments. Sensitivity and specificity were evaluated by identifying patient samples under a wide variety of clinical conditions.
Within-day CVs was <
10% for all analytes tested and between-day CVs ranged from 4.4% to 14.2%. The method was linear in the range between 1.0 and 100 μmol/l for C2 and 0.1 and 10 μmol/l for the other acylcarnitines. The results of the comparison study yielded
r values ranging between 0.948 and 0.999. Recovery ranged from 84% to 112%. The method correctly identified patients with a variety of fatty acid oxidation disorders and organic acidemias.
Our method is a simple procedure for the analysis of acylcarnitines in plasma with minimal sample preparation. It is thus ideal in a routine clinical setting where efficient processing of clinical samples is necessary to reduce turnaround time under conditions of high-throughput.
Heart failure increases the risk of death in acute pulmonary embolism (PE). The role of the left ventricle (LV) in acute PE is not well defined.
To identify the prevalence of LV systolic dysfunction, ...morphology, and prognosis of the LV during an acute PE.
Retrospective study (26-months) of patients diagnosed with an acute PE presenting with LV systolic dysfunction at the University of Maryland.
Among 769 acute PE patients, 78 (10.5 %) had LV systolic dysfunction and 42 (53.8 %) had history of cardiac disease. Patients without history of cardiac disease were younger (mean age SD 54.9 16.8 vs. 62.6 16.6; p = 0.04), had a higher BMI (31.2 12.2 vs. 29.2 7.7; p = 0.005), and less hypertension (20 34.5 % vs. 38 65.5 %; p = 0.0005).
A massive PE was most common in patients without history of cardiac disease (822.2 % vs. 24.7 %, p = 0.02). There was no difference in clot burden, but right ventricular strain was more frequently seen in patients without history cardiac disease in the initial CT (p = 0.001). The median troponin and lactate were similar in both groups.
In 41 patients with follow-up echocardiograms, improvement in LVEF% was observed in patients without cardiac history (median Δ LVEF% IQR; 20 6.2–25.0). While patients with cardiac disease did not demonstrate similar changes (median Δ LVEF% IQR; 0 −5–17.5; p = 0.01). In hospital mortality was 12.8 % with no difference between both groups (p = 0.17).
Pulmonary embolism can be associated with LV systolic dysfunction, even in patients without history of cardiac disease.
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