(Pre)Modern sleep. New evidence from the Antwerp criminal court (1715–1795)

Lately, experts have turned to historical evidence to uncover the default mode of our sleep pattern. Even though there are some notable exceptions, most historians use a qualitative methodology based on scattered evidence in diaries, letters, novels, medical treatise and other literary sources. To provide fresh perspective in the debate, the present article develops a more quantitative approach. Drawing fresh evidence from early modern criminal records – viz the eyewitness reports of the Hoge Vierschaer or the local criminal court in Antwerp – we are able to debunk some classic stereotypes about premodern sleep patterns. Data reveal that most 18^th‐century Antwerpers slept fewer hours than we would expect, slumbered in a monophasic way and rarely if ever took a nap during the day. Moreover, the start and end of sleep were less attuned to the solar cycle than we would imagine. Last but not least, the pattern also shows some fascinating weekly and seasonal variations.     

Identification of the human P450 enzymes involved in the in vitro metabolism of the synthetic steroidal hormones Org 4060 and Org 30659

1. The type of human P450 enzymes involved in the in vitro metabolism of Org 4060 and Org 30659, two synthetic steroidal hormones currently under clinical development by NV Organon for use in oral contraceptive and hormone replacement therapy, was investigated. 2. Both steroids were mainly hydroxylated at the 6 β -position in incubations with human liver microsomes. 3. The results from experiments with supersomes, correlation studies as well as inhibition studies with ketoconazole, a selective inhibitor of CYP3A, strongly suggest that the CYP3A family plays a significant role in the 6 β -hydroxylation of both steroids. 4. Measurements of kinetic parameters of P450 enzymes that could metabolize both steroids, combined with the fact that CYP3A4 is known to be the most abundant P450 enzyme in the human liver, indicate that CYP3A4 will be of major importance for the in vivo human metabolism of Org 4060 and Org 30659.     

Socioeconomic inequalities in lipid and glucose metabolism in early childhood in a population-based cohort: the ABCD-Study

ABSTRACT: BACKGROUND: Socioeconomic inequalities in cardiovascular disease are pervasive, yet much remains to be understood about how they originate. The objective of this study was to explore the relations of socioeconomic status to lipid and glucose metabolism as indicators of cardiovascular health in 5-6 year olds. Additionally to explore the explanatory role of maternal factors, birth outcome, and child factors. METHODS: In 1308 5-6 year old ethnic Dutch children from the ABCD cohort study, lipids (cholesterol, LDL, HDL, triglycerides), glucose and C-peptide were measured after an overnight-fast. RESULTS: There were no differences in cholesterol, HDL, LDL, and triglycerides between socioeconomic groups, as indicated by maternal education and income adequacy. However, children of low educated mothers had on average a higher glucose (beta = 0.15; 95% confidence interval (CI) 0.03 - 0.27), logC-peptide (beta = 0.07; 95% CI 0.04 - 0.09), and calculated insulin resistance (HOMA-IR) (beta = 0.15; 95% CI 0.08 - 0.22) compared to children of high educated mothers. Only childhood BMI partly explained these differences (models controlled for age, height, and sex). CONCLUSIONS: The socioeconomic gradient in cardiovascular risk factors seems to emerge in early childhood. In absence of underlying mechanisms these empirical findings are relevant for public health care and further explanatory research.     

Response of transcortin and alpha 2u-globulin to turpentine-induced inflammation in the rat: influence of corticosteroids and prolactin

Evidence is presented that (transcortin and alpha 2u-globulin react as negative acute-phase proteins in the rat. Thirty-six hours after turpentine injection, the serum concentration of these proteins showed a two- to threefold decrease. Thereafter, transcortin rapidly returned to normal values, whereas alpha 2u-globulin remained low. This reaction pattern was still present after adrenalectomy, adrenalectomy and administration of glucocorticoids, and after treatment with bromocriptine, a suppressor of prolactin secretion. It is concluded that changes in the secretion of glucocorticoids and prolactin are not required for the observed turpentine-induced decrease of transcortin and alpha 2u-globulin.     

Risk factors for urological symptoms in a cohort of users of the HIV protease inhibitor indinavir sulfate: the ATHENA cohort

BACKGROUND: Nephrolithiasis is a well-known complication of indinavir treatment and may result in urological symptoms ranging from renal colic to renal insufficiency. OBJECTIVE: To obtain further knowledge regarding the incidence and risk factors of urological symptoms associated with indinavir sulfate use. METHODS: This study was performed in the ATHENA (AIDS Therapy Evaluation National AIDS Therapy Evaluation Centre) cohort of patients infected with human immunodeficiency virus (HIV) receiving antiretroviral therapy in the Netherlands. The incidence rate of urological symptoms was assessed in a subcohort of 1219 patients starting HIV protease inhibitor treatment after 1996. Urological symptoms were defined as an initial report of nephrolithiasis, renal colic, flank pain, hematuria, renal insufficiency, or nephropathy. Using multivariate Cox regression analysis, risk factors for urological symptoms during indinavir treatment were subsequently studied among the subset of 644 patients who started indinavir treatment after 1996. RESULTS: The incidence of urological symptoms was 8.3 per 100 treatment-years for indinavir vs 0.8 per 100 treatment-years for other HIV protease inhibitors. Risk factors for urological symptoms during indinavir treatment were low weight (relative risk [RR], 2.1; 95% confidence interval [CI], 1.1-3.9), low lean body mass (RR, 1.7; 95% CI, 1.0-2.9), undetectable HIV-1 RNA when starting indinavir treatment (RR, 3.2; 95% CI, 1.5-6.0), prior treatment change because of intolerance (RR, 2.4; 95% CI, 1.2-5.1), indinavir regimens of 1000 mg or more twice daily (RR, 3.1; 95% CI, 1.3-8.2), and warm environmental temperatures (RR, 3.9; 95% CI, 1.7-8.8). Risk estimates were highest among patients with a low lean body mass. CONCLUSION: Increased alertness for urological symptoms is warranted for patients starting indinavir treatment, particularly among those with a low lean body mass, during indinavir regimens of 1000 mg or more twice daily, and in warm weather environments.     

UV-C irradiation disrupts platelet surface disulfide bonds and activates the platelet integrin alphaIIbbeta3

UV-C irradiation has been shown to be effective for pathogen reduction in platelet concentrates, but preliminary work indicated that UV-C irradiation of platelets can induce platelet aggregation. In this study, the mechanism underlying this phenomenon was investigated. Irradiation of platelets with UV-C light (1500 J/m(2)) caused platelet aggregation, which was dependent on integrin alphaIIbbeta3 activation (GPIIb/IIIa). This activation occurred despite treatment with several signal transduction inhibitors known to block platelet activation. UV-C also induced activation of recombinant alphaIIbbeta3 in Chinese hamster ovary (CHO) cells, an environment in which physiologic agonists fail to activate. Activation of alphaIIbbeta3 requires talin binding to the beta3 tail, yet alphaIIbbeta3-Delta724 (lacking the talin binding site) was activated by UV-C irradiation, excluding a requirement for talin binding. The UV-C effect appears to be general in that beta(1) and beta(2) integrins are also activated by UV-C. To explain these findings, we investigated the possibility of UV-C-induced photolysis of disulfide bonds, in analogy with the activating effect of reducing agents on integrins. Indeed, UV-C induced a marked increase in free thiol groups in platelet surface proteins including alphaIIbbeta3. Thus, UV-C appears to activate alphaIIbbeta3 not by affecting intracellular signal transduction, but by reduction of disulfide bonds regulating integrin conformation.