Minimal analytical characterization of engineered nanomaterials needed for hazard assessment in biological matrices.

This paper presents the outcomes from a workshop of the European Network on the Health and Environmental Impact of Nanomaterials (NanoImpactNet). During the workshop, 45 experts in the field of safety assessment of engineered nanomaterials addressed the need to systematically study sets of engineered nanomaterials with specific metrics to generate a data set which would allow the establishment of dose-response relations. The group concluded that international cooperation and worldwide standardization of terminology, reference materials and protocols are needed to make progress in establishing lists of essential metrics.

Isolation and in vitro chondrogenic potential of human foetal spine cells.

Cell therapy for nucleus pulposus (NP) regeneration is an attractive treatment for early disc degeneration as shown by studies using autologous NP cells or stem cells. Another potential source of cells is foetal cells. We investigated the feasibility of isolating foetal cells from human foetal spine tissues and assessed their chondrogenic potential in alginate bead cultures.

Interleukin-6 and tumor necrosis factor alpha levels after bisphosphonates treatment in vitro and in patients with malignancy.

Bisphosphonates are potent inhibitors of bone resorption and are widely used in the treatment of bone diseases. One of the side effects of administered aminobisphosphonates is transient fever and some biological changes that are suggestive of an acute phase response. Pamidronate [(3-amino-1-hydroxypropylidene).

Astrocytes secrete a factor inducing the expression of HT7-protein and neurothelin in endothelial cells of chorioallantoic vessels.

Among the most specific markers of the blood-brain barrier phenotype of endothelial cells are the well-characterized immunoglobulin-like surface glycoprotein HT7 and the probably related or identical glycoprotein neurothelin. Both can be induced in chorioallantoic vessels by transplants of embryonic mouse brain. Other blood-brain barrier markers have been shown to be inducible by type-1 astrocytes in endothelial cells of non-neural origin.

Effect of the renin response during renin inhibition: oral Ro 42-5892 in normal humans.

The effect of the new renin inhibitor Ro 42-5892 was evaluated in healthy volunteers after both intravenous and oral administration. In a preliminary study, 14 subjects received a 10-min infusion of Ro 42-5892 at doses ranging from 0.001 to 1 mg/kg.

Determinants of angiotensin II generation during converting enzyme inhibition.

The reaction of the renin-angiotensin system to acute angiotensin converting enzyme inhibition was investigated in a single-blind, crossover study in nine normal volunteers receiving two out of three regimens in random order: the new converting enzyme inhibitor benazepril (20 mg once or 5 mg four times at 6-hour intervals) or enalapril (20 mg). Plasma converting enzyme activity, drug levels, angiotensin I and angiotensin II, active renin, and aldosterone were measured before and 1-4 hours and 14-30 hours after drug intake. Baseline in vitro plasma converting enzyme activity was 97 +/- 15 nmol/ml/min (mean +/- SD) when Hip-Gly-Gly was used as substrate, but with carbobenzoxy-Phe-His-Leu (Z-Phe-His-Leu) or angiotensin I as substrate it was only 20 +/- 4 and 1.

Caffeine-induced diuresis and atrial natriuretic peptides.

After a single-blind, randomized, cross-over protocol using decaffeinated coffee in a control experiment, the effect of an oral 250-mg caffeine dose on plasma immunoreactive atrial natriuretic peptide (ANF) was assessed in eight healthy students who had been on a methylxanthine-free diet for 1 week. One to 2 h after caffeine ingestion, both systolic blood pressure (SBP) and diastolic BP (DBP) increased by 12 mm Hg while heart rate (HR) also tended to increase. An increase in diuresis and in urinary sodium, potassium, and osmol excretion was observed within 1 h.

Reactive hyperreninemia is a major determinant of plasma angiotensin II during ACE inhibition.

The new ACE inhibitor trandolapril was administered to normal volunteers at daily doses of 0.5, 2, and 8 mg for 10 days. Twenty-one volunteers, aged 21-30 years, were included in the study.

Prevention of renal hypertension in the rat by neuropeptide Y.

Neuropeptide Y is known to enhance blood pressure responsiveness to various constrictors, including angiotensin II, and to suppress renin secretion. This study was undertaken to assess the effect of neuropeptide Y on the development of two-kidney, one clip renal hypertension. Normotensive rats either had a silver clip placed on the left renal artery or were sham-operated upon.

Effects of smoking and physical exercise on platelet free cytosolic calcium in healthy normotensive volunteers.

Platelet free cytosolic calcium (PFCC) was measured in 21 healthy volunteers before and after cigarette smoking or physical exercise. The aim was to investigate whether acute blood pressure changes and increases in circulating levels of catecholamines and vasopressin modify PFCC. PFCC was determined using the Quin-2 method.

Need for plasma angiotensin measurements to investigate converting-enzyme inhibition in humans.

Since only a minute proportion of total angiotensin-converting enzyme (ACE) is present in plasma, the reliability of conventional in vitro measurements of ACE activity has been questioned. Data presented here demonstrate that the definition of ACE inhibition depends on the methodology used, with different results obtained with different substrates. We have developed a method that provides accurate and precise determinations of "true" angiotensin levels and in vivo ACE activity was estimated by measuring the plasma angiotensin II/angiotensin I ratio.

Angiotensin converting enzyme inhibition: discrepancy between antihypertensive effect and suppression of enzyme activity.

With chronic angiotensin converting enzyme (ACE) inhibition, blood pressure remains controlled throughout the day despite intermittent recovery of normal function of the renin-angiotensin system. This has been taken as evidence to suggest that the disappearance of angiotensin II (Ang II) from the circulation is not the main mechanism involved in the blood pressure-lowering action of ACE inhibitors. However, the degree of ACE inhibition is often not reliably estimated by the commonly used measurements of plasma ACE activity in vitro or plasma immunoreactive Ang II levels.

Increased response of brachial artery diameter to norepinephrine in hypertensive patients.

The hyperresponsiveness of small arteries to norepinephrine is well documented in essential hypertensive patients. Our objective was to investigate in situ the reactivity to norepinephrine of the diameter of large arteries, which are involved in the arterial disease of hypertension as well as small arteries. Brachial artery diameter, blood flow velocity, local volumic blood flow, and local vascular resistances were determined noninvasively with a pulsed Doppler system in 19 patients with essential hypertension and 9 normotensive subjects, before and after the administration of placebo (glucose) or increasing doses of norepinephrine (10, 20, and 40 ng.

[Hyperreactivity of the humeral artery to noradrenaline in essential hypertension patients].

The hyperresponsiveness of small arteries to norepinephrine is well documented in essential hypertensive patients. Our objective was to investigate in situ the reactivity to norepinephrine of the diameter of large arteries which are involved in the arterial disease of hypertension as well as small arteries. Brachial artery diameter, blood flow velocity, local volumic blood flow and local vascular resistances were determined non invasively using a pulsed Doppler system in 19 patients with essential hypertension and 9 normotensive subjects, before and after placebo (glucose) or increasing doses of norepinephrine (10, 20 and 40 ng/kg/min; i.

Rapid measurement of total and active renin: plasma concentrations during acute and sustained converting enzyme inhibition with CGS 14824A.

Total and active renin were measured in plasma of 6 normal volunteers before and after acute and sustained angiotensin converting enzyme (ACE) inhibition with CGS 14824A (2 mg and 10 mg p.o. q.