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The varied transcriptomic response to nanoparticles has hampered the understanding of the mechanism of action. Here, by performing a meta-analysis of a large collection of transcriptomics data from various engineered nanoparticle exposure studies, we identify common patterns of gene regulation that impact the transcriptomic response. Analysis identifies deregulation of immune functions as a prominent response across different exposure studies. Looking at the promoter regions of these genes, a set of binding sites for zinc finger transcription factors C2H2, involved in cell stress responses, protein misfolding and chromatin remodelling and immunomodulation, is identified. The model can be used to explain the outcomes of mechanism of action and is observed across a range of species indicating this is a conserved part of the innate immune system.

We present a realistic molecular-dynamics treatment of laser-cooled ions in radio-frequency ion traps which avoids previously made simplifications such as modeling laser cooling as a friction force and combining individual heating mechanisms into a single effective heating force. Based on this implementation, we show that infrequent energetic collisions of single ions with background gas molecules lead to pronounced heating of the entire ion ensemble and a time-varying secular ensemble temperature, which manifests itself in a superstatistical time-averaged velocity distribution of the ions. The effect of this finding on the experimental determination of ion temperatures and rate constants for cold chemical reactions is discussed. [ABSTRACT FROM AUTHOR]

1. Attenuation of the effectiveness of antihypertensive therapy by non-steroidal antiinflammatory (NSAI) drugs has been attributed to inhibition of systemic or renal vasodilator prostaglandin synthesis, or a combination of both. 2. Indomethacin is a NSAI drug with both renal and extrarenal cyclo-oxygenase inhibition properties. Sulindac is a relatively selective cyclooxygenase inhibitor said not to affect urinary prostaglandin excretion. 3. This study examines the relative effect on blood pressure of 4 weeks' treatment, with indomethacin 25 mg three times daily and sulindac 200 mg twice daily, in a randomized placebo controlled trial in 26 hypertensive subjects. 4. In nine patients treated with indomethacin, supine blood pressure rose 11 mmHg systolic and 4 mmHg diastolic by the end of the first week, whereas nine subjects treated with sulindac showed a fall in blood pressure similar to the trend seen in placebo-treated subjects. 5. Indomethacin treatment inhibited renal cyclo-oxygenase with a 78% reduction in urinary prostaglandin E2 excretion and 89% suppression of plasma renin activity. Neither measurement was affected by sulindac. Extrarenal cyclo-oxygenase activity was inhibited by both indomethacin and sulindac with serum thromboxane B2 decreasing by 96% and 69% respectively. 6. The results suggest that the pressor effect of NSAI drugs is predominantly related to renal cyclo-oxygenase inhibition. The lack of effect of sulindac on blood pressure may make it a safer therapeutic option if NSAI drug therapy is necessary in the hypertensive patient.

1. Measurement of urinary 6-ketoprostaglandin (PG) F1α and PGE2 excretion in 83 healthy children, aged 5-15 years, revealed that supervised 4 h urine collections under mild water diuresis provided more consistent results than overnight 12 h urine collections. 2. Males had higher urinary excretion of 6-keto-PGF1α but not of PGE2 compared with females. 3. Urinary potassium was related to 6-keto-PGF1α in both 4 and 12 h urine collections and urinary sodium to 6-keto-PGFα in 4 h collections only. 4. In the sexes combined multiple regression analyses revealed age as the only significant influence on prostanoid excretion (P = 0.001). 5. Thus age and sex and dietary potassium intake need to be considered in studies of urinary prostanoids in children.

1. Resting and stimulated plasma noradrenaline and adrenaline concentration were compared in 45 females and 45 males of similar age who did not smoke, drink alcohol or caffeine-containing beverages. 2. At rest plasma noradrenaline levels were consistently higher in females and adrenaline levels higher in males. These sex-related differences were maintained after isometric exercise, mental arithmetic and cold pressor testing. 3. Resting noradrenaline concentration was negatively correlated with Quetelet index in males and positively correlated with age in females. 4. These findings, based on precise catecholamine measurements under standardized conditions in subjects of similar age, reveal important sex-related differences which need to be taken into account in assessing sympatho-adrenal activity, particularly in relation to mechanisms in essential hypertension.

1. This study examines the response of blood pressure, plasma catecholamines and cortisol to acute alcohol intake in young men with light to moderate drinking habits. 2. Ingestion of alcohol was associated with a highly significant increase in systolic blood pressure and heart rate which occurred before blood alcohol reached its peak concentration of 16.9 ± 1.1 mmol/l (80 mg/100 ml). After an initial non-specific rise, diastolic pressure fell below values observed after drinking water only. This predominant effect of alcohol on systolic blood pressure is also seen with chronic alcohol consumption. 3. Drinking water and non-alcoholic cold liquids caused a marked fall in plasma adrenaline and a transient rise in noradrenaline concentration. In contrast, drinking alcohol resulted in a relative rise in adrenaline and a delayed increase in noradrenaline concentration. 4. Blood glucose increased after alcohol, supporting a physiological effect of adrenaline on liver glycogenolysis. Plasma cortisol concentration was also significantly higher after drinking alcohol. 5. It is proposed that the relative rise in adrenaline together with higher cortisol levels, repeated over a variable period in susceptible individuals, are implicated in the elevation of blood pressure associated with long term alcohol consumption. It concurs with observations in man and experimental animals of a slow pressor mechanism mediated by adrenaline. 6. The study emphasized that an evaluation of the acute effects of alcohol requires careful measurement of blood pressure, precise assay of catecholamines and recognition of the confounding effects of drinking cold liquids.

1. At present it is unclear whether platelet-activating-factor (PAF)-induced aggregation is mediated by thromboxane. To obtain further information about this event we have compared the affects of aspirin on platelet aggregation and secretion induced by PAF and collagen. 2. Collagen and PAF induced aggregation and secretion in human platelets in a dose-related manner. 3. Aspirin inhibited the magnitude of both platelet aggregation and secretion induced by PAF and collagen, but the degree of inhibition was much greater for collagen. 4. Aspirin strongly inhibited the aggregation rate of collagen-induced platelet aggregation, but had no measurable effect on the rate of PAF-induced aggregation. 5. Inconsistencies reported in previous studies of the effect of aspirin on PAF-induced platelet aggregation may be explained, in part, by the doses of PAF used and the method of inactivating cyclo-oxygenase (in vitro compared with in vivo). 6. Our results suggest that the initial events of PAF-induced aggregation are independent of thromboxane A2 formation and that thromboxane A2 plays only a minor role in the later phase of PAF-induced aggregation.

Diurnal patterns of blood pressure and pressor hormones after 26 weeks gestation were compared in 10 normotensive women, 13 subjects with uncomplicated hypertension, and 8 with biochemical evidence of pre-eclampsia. 4 of the pre-eclamptics showed nocturnal hypertension.Levels of plasma renin activity fell progressively from 9 a.m. to midnight in all three groups, and were significantly lower in pre-eclampsia.Plasma angiotensin II levels fell during the day in normotensives and uncomplicated hypertensives, whereas pre-eclamptics showed loss of this pattern and significantly lower levels than the other groups.Free plasma norepinephrine levels fell during the day and to a similar extent in all three groups.A diurnal pattern for free plasma norepinephrine levels, with lower levels at midnight than during the day, was seen in normotensives and uncomplicated hypertensives but not in pre-eclamptics.Plasma norepinephrine sulphate levels rose from 9.00 a.m. to midnight in normotensives and uncomplicated hypertensives. This pattern was reversed in pre-eclamptics, including 3 of the 4 subjects with nocturnal hypertension.Plasma epinephrine sulphate levels rose progressively through the day, with no significant differences between groups.Failure of plasma angiotensin II or epinephrine levels to fall at night in pre-eclampsia may contribute to nocturnal hypertension in subjects with increased vascular reactivity. Suppression of plasma renin activity and angiotensin II levels suggests that perhaps as yet unidentified pressor mechanisms are involved in pre-eclampsia.The "GLIM" System. 3. Generalized Linear interactive modelling. Manual by Baher R J and Nelder J A 1970. Copyright Royal Statistical Society UK. Distributed by Numerical Algorlthms Joday, Oxford.

1. The association between alcohol consumption and blood pressure was studied in 491 Government employees. The men, aged 21–45 years, volunteered to complete a health questionnaire and submitted to standardized measurements of blood pressure, heart rate and body size. 2. Average weekly alcohol consumption correlated with systolic pressure (r = 0.18, P < 0.001) but not with diastolic pressure. Systolic pressure increased progressively with increasing alcohol consumption with no obvious threshold effect. The effect of alcohol was independent of age, obesity (Quetelet's index) or cigarette smoking. 3. Results indicate that alcohol ranks close to obesity as a preventable cause of essential hypertension in the community.