Impact of the spacer on the condensing effect of fluorinated chains investigated by grazing incidence X-ray diffraction on ultrathin Langmuir monolayers.

Langmuir monolayers of double perfluoroalkyl(alkyl) chain amphiphiles fitted with a monomorpholinophosphate polar head, [C(n)F(2n+1)(CH(2))(m)O](2)P(O)[N(CH(2)CH(2))(2)O] (di(FnHm)MP with n = 6, 8, or 9; and m = 1 or 2), were investigated by surface pressure (π)/molecular area (A(0)) compression isotherms for temperatures ranging from 15 to 50 °C, and by grazing-incidence X-ray diffraction (GIXD) at 25 °C. Ultrathin monolayers were obtained for these short surfactants. Though the hydrocarbon spacer is short, it has a remarkable impact on the monolayer's organization. At 25 °C, whereas di(F8H2)MP monolayer presents a liquid expanded (LE)/liquid condensed (LC) transition, simply replacing one CH(2) by a CF(2) in the latter compound's structure at constant chain length, i.e. shortening the spacer from 2 to 1 CH(2) (as in di(F9H1)MP), suppresses the LE phase. At 25°, GIXD established that for both di(F8H2)MP and di(F9H1)MP, the chains form an hexagonal lattice in the LC phase. The collective tilt of the two compounds is close to zero. The lattice of the dense phase can be compressed, as assessed by the continuous linear decrease of the d spacing with increasing pressure. This indicates that the azimuthal distribution of the molecular tilts is progressively reduced upon compression. The d value for di(F9H1)MP is significantly lower than that of di(F8H2)MP, providing evidence for strong condensing effect of the fluorinated chains. Molecular areas were determined directly from the compression curves and also from the X-ray data, the latter allowing reconstruction of the compression isotherms. The calculated lattice compressibilities are ~30% and 50% of the macroscopic compressibilities for di(F9H1)MP and di(F8H2)MP, respectively. Comparison with the experimentally determined isotherms shows that the monolayer of di(F9H1)MP is more stable than that of di(F8H2)MP. The enthalpies and entropies determined for di(F9H1)MP and di(F8H2)MP, derived from the Clausius-Clapeyron equation, confirm that the observed transitions are both of the LE/LC type, although the triple point temperatures are strikingly different (27 °C vs -18 °C); this large difference further illustrates the stabilizing effect of the fluorinated chains. Disorder is hindered by the fluorinated chains and facilitated by a hydrocarbon spacer when larger than 1 CH(2).

Improved in vivo two-photon imaging after blood replacement by perfluorocarbon.

Two-photon microscopy is a powerful method in biomedical research that allows functional and anatomical imaging at a subcellular resolution in vivo. The technique is seriously hampered by absorption and scattering of light by blood, which prevents imaging through large vessels. Here, we demonstrate in the rat cerebral cortex that blood replacement by perfluorocarbon emulsion, a compound also used in human critical care medicine, yields superior image quality, while preserving neuronal integrity. Shadows of large superficial vessels disappear completely and cells can be imaged underneath them. For the first time, it is possible to image complete populations of neurons and astrocytes in the upper layers of neocortex in vivo.

Temperature measurements in carbonatite lava lakes and flows from oldoinyo lengai, Tanzania.

The petrogenesis of carbonatites has important implications for mantle processes and for the magmatic evolution of mantle melts rich in carbon dioxide. Oldoinyo Lengai, Tanzania, is the only active carbonatite volcano on Earth. Its highly alkalic, sodium-rich lava, although different in composition from the more common calcium-rich carbonatites, provides the opportunity for observations of the physical characteristics of carbonatite melts. Temperature measurements on active carbonatitic lava flows and from carbonatitic lava lakes were carried out during a period of effusive activity in June 1988. Temperatures ranged from 491 degrees to 519 degrees C. The highest temperature, measured from a carbonatitic lava lake, was 544 degrees C. These temperatures are several hundred degrees lower than measurements from any silicate lava. At the observed temperatures, the carbonatite melt had lower viscosities than the most fluid basaltic lavas. The unusually low magmatic temperatures were confirmed with 1-atmosphere melting experiments on natural samples.

Perfluorocarbons: new tool for islets preservation in vitro.

Pancreatic islet transplantations to treat type 1 diabetes often fail to function because of hypoxia. Perfluorocarbons (PFCs) exhibit a high oxygen solubility coefficient and maintain high oxygen partial pressure for extended times. They also serve as oxygen "reservoirs" for harvested organs in pancreas organ transplantation. Previous studies have shown the PFCs display antiadhesive effects on beta cells. The aim of this study was to evaluate the effects of PFC on islet viability and functionality and on extracellular matrix (ECM) disruption of islets via inhibition of adhesion. Primary cultures of rat islets were incubated for 24 hours in the presence or absence of 3.5% (weight/volume) PFCs in culture media. We studied viability (FDA/PI), stimulation index linked to insulin secretion (ELISA), and expression of insulin and laminin messenger RNAs (mRNAs). Immunostaining was performed on insulin and laminin. Islet viability was similar in the presence or absence of PFCs (about 80%). Stimulation index showed preservation of islet functionality in the presence of PFC (4.9 +/- 0.7) as compared with controls (2.8 +/- 0.5). Moreover, laminin mRNA expression was lower compared with controls (55% of PFC incubated vs control islets). Immunohistochemistry studies showed preservation of ECM inside the islets in the presence of PFCs versus controls at 24 hours after islet isolation. In conclusion, PFCs preserved islet viability and functionality and prevented ECM disruption. PFCs may represent a new tool for islet preservation in vitro.

Newer Oral Anticoagulants in the Treatment of Acute Portal Vein Thrombosis in Patients with and without Cirrhosis.

BACKGROUND: Newer oral anticoagulants (NOACs) are being utilized increasingly for the treatment of venous thromboembolism (VTE). NOAC use is the standard of care for stroke prophylaxis in nonvalvular atrial fibrillation and treatment of acute VTE involving extremities and pulmonary embolism. In contrast, most guidelines in the literature support the treatment of acute portal vein thrombosis (PVT) with low molecular weight heparin (LMWH) and vitamin K antagonists (VKA). Literature evaluating NOAC use in the treatment of acute portal vein thrombosis is sparse. This review focuses on the safety and efficacy of the use of NOACs in the treatment of acute PVT in patients, with or without concomitant cirrhosis, based on the most recent data available in the current literature. METHODS: A systematic review was conducted through a series of advanced searches in the following medical databases: PubMed, BioMed Central, Cochrane, and Google Scholar. Keywords utilized were as follows: NOAC, DOAC (direct oral anticoagulants), portal vein thrombosis, rivaroxaban, apixaban, dabigatran, and edoxaban. Articles related to newer anticoagulant use in patients with portal vein thrombosis were included. RESULTS: The adverse events, including bleeding events (major and minor) and the failure of anticoagulation (propagation of thrombus or recurrence of PVT), are similar between the NOACs and traditional anticoagulants for the treatment of acute PVT, irrespective of the presence of cirrhosis. CONCLUSIONS: Newer oral anticoagulants are safe and efficacious alternatives to traditional anticoagulation with low molecular weight heparin and vitamin K antagonists in the treatment of acute portal vein thrombosis with or without cirrhosis.

Fluorocarbon/lecithin emulsions: identification of EYP-coated fluorocarbon droplets and fluorocarbon-empty vesicles by freeze-fracture electron microscopy.

Freeze-fracture has been used to examine perfluorodecalin/egg yolk phospholipid emulsions (70:8, w/v%) destined to be used as injectable oxygen carriers. The fluorocarbon displays a specific granular aspect upon freeze-fracture which makes it readily recognizable and allows the distinction between two populations of objects on the micrographs: fluorocarbon droplets and water-filled lipid vesicles.

Fluorocarbons and fluorinated amphiphiles in drug delivery and biomedical research.

The specific properties of fluorocarbons, exceptional chemical and biological inertness, high gas-dissolving capacity, low surface tension, excellent spreading characteristics and high fluidity, have triggered numerous applications of these compounds in oxygen delivery. An injectable emulsion of fluorocarbon-in-water destined to deliver oxygen to tissues at risk of hypoxia has now completed Phase III clinical trials in Europe. A neat fluorocarbon is currently investigated in Phase II for treatment of acute respiratory failure by liquid ventilation. Fluorinated lipids and fluorinated surfactants can be used to elaborate and stabilize various colloidal systems, including different types of emulsions, vesicles and tubules, that also show promise for controlled release drug delivery.

Highly fluorinated amphiphiles and colloidal systems, and their applications in the biomedical field. A contribution.

Fluorocarbons and fluorocarbon moieties are uniquely characterized by very strong intramolecular bonds and very weak intermolecular interactions. This results in a combination of exceptional thermal, chemical and biological inertness, low surface tension, high fluidity, excellent spreading characteristics, low solubility in water, and high gas dissolving capacities, which are the basis for innovative applications in the biomedical field. Perfluoroalkyl chains are larger and more rigid than their hydrogenated counterparts. They are considerably more hydrophobic, and are lipophobic as well. A large variety of well-defined, modular fluorinated surfactants whose polar head groups consist of polyols, sugars, sugar phosphates, amino acids, amine oxides, phosphocholine, phosphatidylcholine, etc, has recently been synthesized. Fluorinated surfactants are significantly more surface active than their hydrocarbon counterparts, both in terms of effectiveness and of efficiency. Despite this, they are less hemolytic and less detergent. Fluorosurfactants appear unable to extract membrane proteins. Fluorinated chains confer to surfactants a powerful driving force for collecting and organizing at interfaces. As compared to non-fluorinated analogs, fluorosurfactants have also a much stronger capacity to self-aggregate into discrete molecular assemblies when dispersed in water and other solvents. Even very short, single-chain fluorinated amphiphiles can form highly stable, heat-sterilizable vesicles, without the need for supplementary associative interactions. Sturdy microtubules were obtained from non-chiral, non-hydrogen bonding single-chain fluorosurfactants. Fluorinated amphiphiles can be used to engineer a variety of colloidal systems and manipulate their morphology, structure and properties. Stable fluorinated films, membranes and vesicles can also be prepared from combinations of standard surfactants with fluorocarbon/hydrocarbon diblock molecules. In bilayer membranes made from fluorinated amphiphiles the fluorinated tails segregate to form an internal teflon-like hydrophobic and lipophobic film that increases the stability of the membrane and reduces its permeability. This fluorinated film can also influence the behavior of fluorinated vesicles in a biological milieu. For example, it can affect the in vivo recognition and fate of particles, or the enzymatic hydrolysis of phospholipid components. Major applications of fluorocarbons currently in advanced clinical trials include injectable emulsions for delivering oxygen to tissues at risk of hypoxia; a neat fluorocarbon for treatment of acute respiratory failure by liquid ventilation; and gaseous fluorocarbon-stabilized microbubbles for use as contrast agents for ultrasound imaging. Fluorosurfactants also allow the preparation of a range of stable direct and reverse emulsions, microemulsions, multiple emulsions, and gels, some of which may include fluorocarbon and hydrocarbon and aqueous phases simultaneously. Highly fluorinated systems have potential for the delivery of drugs, prodrugs, vaccines, genes, markers, contrast agents and other materials.

Perfluoroalkylphosphocholines are poor protein-solubilizing surfactants, as tested with neutrophil plasma membranes.

We have tested the membrane-protein solubilizing properties of two perfluoroalkylphosphocholines. These compounds belong to a series of fluorinated amphiphiles which are being investigated as potential stabilizing agents for a variety of fluorocarbon-based systems. We are particularly interested in cytochrome b558 from phagocytes, the redox component of NADPH oxidase. Its heavy subunit is believed to carry binding sites for NADPH and FAD. Nevertheless, when the cytochrome is purified in the presence of classical detergents, it carries no FAD. This could be due to a delipidating, denaturing effect of these detergents (octyl glucoside, Triton, etc). The first perfluoroalkyphosphocholine, C8F17(CH2)2O-P(O2-)-O(CH2)2N+(CH3)3(F8C2PC), extracted about as much protein from neutrophil plasma membranes into a 100,000 g supernatant as octyl glucoside. The second compound, C8F17(CH2)11O-P(O2-)-O(CH2)2N+(CH3)3(F8C11PC), was less efficient. We found that flavin was still protein-bound in the crude F8C2PC extract at a FAD to heme ratio of about 1, and a good NADPH oxidase activity was obtained without addition of exogenous FAD, even after dialysis or gel filtration, whereas dialysis eliminated most of the FAD from the octyl glucoside extracts. These experiments appeared to make F8C2PC an interesting membrane-solubilizing agent. Nevertheless, no protein in the F8C2PC extract could be adsorbed on the chromatographic supports normally used for purification. After dilution of the extract and addition of 15 mM octyl glucoside, some of the proteins, such as myeloperoxidase, could be adsorbed (and eluted), but not cytochrome b558. Freeze-fracture electron microscopy showed that the F8C2PC extracts contained numerous vesicles and aggregates of small shapeless particles. Higher centrifugal forces sedimented most proteins of the 100,000 g supernatant. As a check, the effect of F8C2PC was tested on sarcoplasmic reticulum vesicles, the behavior of which with respect to the usual non-denaturating detergents has been well studied. There was little, if any, solubilization. We conclude that, although supernatants of F8C2PC extracts of neutrophil membranes are optically clear, proteins are not really solubilized. This result is in keeping with the absence of lytic effects of F8C2PC on erythrocyte membranes.

Injury severity assessment for car occupants in frontal impacts, using disability scaling.

Injury classification and assessment is one of the most important fields of injury prevention. At present, injury assessment focuses primarily on the risk of fatalities, in spite of the fact that most people who are injured survive the trauma. The net result of a fatality-based approach is that safety and vehicle engineers must make decisions with an incomplete, and sometimes misleading, picture of the traffic safety problem. By applying disability scaling reflecting long-term consequences to injury data, the most significant disabling injuries can be identified. The priorities change with the level of disability used in the scaling. In this study, the risk of permanent medical disability due to different injuries was derived and linked to abbreviated injury scale (AIS) values for 24,087 different injured body regions. This material is based on insurance data. To study how the importance of different bodily injuries changes with different severity assessments in a realistic real-world injury distribution, Swedish insurance industry disability scaling was applied to 3066 cases of belted Volvo drivers involved in frontal collisions. Crash severity was included in the study by using equivalent barrier speed (EBS). When lower levels of disability are included, injuries to the neck and the extremities become the most important, while brain and skull injuries become the most prominent at higher levels of disability. The results presented in this article should be regarded as a contribution to the development of a suitable disability scaling method. The results can also be utilized to further injury research and vehicle design aimed at reducing injuries which have the most important long-term disability consequences.

Fluorinated materials for in vivo oxygen transport (blood substitutes), diagnosis and drug delivery.

Fluorocarbons are characterized by exceptional chemical and biological inertness, extreme hydrophobicity, lipophobicity, high gas-dissolving capacities, low surface tensions, high fluidity and spreading coefficients, high density, absence of protons, and magnetic susceptibilities comparable to that of water. These unique properties are the foundation for a range of biomedical applications. An injectable fluorocarbon-in-water emulsion is in advanced clinical trials as a temporary oxygen carrier (blood substitute) to prevent tissue hypoxia or ischemia in the surgical and critical care patient. A liquid fluorocarbon is in Phase II/III clinical trials for treatment of acute respiratory failure through liquid ventilation. Several fluorocarbon-based contrast agents for ultra-sound imaging are in various stages of clinical investigation. Multiple families of well-defined pure fluorinated surfactants have recently been synthesized. These surfactants have a modular structure which allows stepwise adjustment of their physicochemical characteristics. Their polar head group derives from polyols, sugars, aminoacids, amides, amine oxides, phosphocholine, phosphatidylcholine, etc. Fluorinated surfactants are significantly more surface-active than their hydrocarbon analogs and they display a greater tendency to self-assemble, thus forming well-ordered, stable supramolecular assemblies such as vesicles, tubules, fibers, ribbons, etc. Fluorinated amphiphiles also allowed the obtaining of a variety of stable reverse and multiple emulsions and gels. These systems are being investigated as drug delivery devices.

Evaluation of cytotoxicity of new semi-fluorinated amphiphiles derived from dimorpholinophosphate.

Water-in-fluorocarbon reverse emulsions and microemulsions stabilized by semi-fluorinated amphiphiles derived from the dimorpholinophosphate polar head group, C(n)F(2n+1)(CH(2))(m)OP(O)[N(CH(2)CH(2))(2)O](2) (FnHmDMP), are being investigated as new delivery systems for drugs or genetic materials into the lung. Since information related to the toxicity of fluorinated surfactants is still very limited, we evaluated herein the cytotoxicity of a series of FnHmDMP (n=4, 6, 8 and 10 and m=2, 5, and 11). Both solutions of FnHmDMP in fluorocarbons, and reverse water-in-fluorocarbon emulsions stabilized by FnHmDMP were assessed in order to determine the relation between surfactant structure and cell toxicity, and select the most innocuous emulsifier. A first short-term evaluation on mouse fibroblasts using a viability/cytotoxicity assay indicated that amphiphiles (in solution) with a chain length longer than C12 exhibit less toxicity than amphiphiles with shorter chain. Moreover cytotoxicity decreased also with length of the fluorinated segment. The protective effect of the fluorinated chain was strongly supported by the fact that the hydrogenated analog, C(15)H(31)OP(O)[N(CH(2)CH(2))(2)O](2) (H15DMP), was highly toxic. Qualitative evaluation on human lung epithelial cells (HLEC) using a colorimetric method (Mayer's hematoxylin) confirmed that amphiphiles (in solution) with longer chain were the least cytotoxic. The protective effect of the fluorinated chain appeared, however, to be significant only at low amphiphile concentrations (0.1% w/v). In contrast, at higher concentrations (1% and 5% w/v), the total chain length was the determining factor. Quantitative evaluation of the least cytotoxic amphiphiles using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method then showed that F10H11DMP (in solution) was harmless until its solubility limit (1% w/v); cell growth was even enhanced due to improved oxygenation provided by the fluorocarbon phase. F8H11DMP exhibited some cytotoxicity at both 1% and 5% w/v, but the toxicity appeared to level off with concentration. Reverse water-in-perfluorooctyl bromide (PFOB) emulsions stabilized by either F10H11DMP or F8H11DMP were found to be non-cytotoxic. In conclusion, the present evaluation indicates that the cytotoxicity of FnHmDMP depends on both total and fluorinated amphiphile chain length, and leads us to select F8H11DMP and F10H11DMP as the less cytotoxic amphiphiles among a series of FnHmDMP compounds. Furthermore, water-in-fluorocarbon emulsions stabilized with F8H11DMP and F10H11DMP appeared to be non-cytotoxic towards HLEC in culture.

Effect of aging on estimates of hypercapnic ventilatory response during sleep.

By recording only inspired PCO2 (PICO2) in a hood and transcutaneous PCO2 (PsCO2) the Hazinski method was used to estimate nonintrusively the slope (Sr) per Torr PsCO2 of the fractional ventilatory response to approximately 18 and 30 Torr PICO2 in 17 healthy elderly subjects (10 women) and 17 younger controls (9 women) during wakefulness, slow-wave sleep (SWS), and rapid-eye-movement (REM) sleep. Eight of the older subjects had sleep disturbance indexes (RDI) greater than 5. Sr fell with SWS from 0.90 +/- 0.34 to 0.60 +/- 0.29 (P less than 0.006) in the younger group (n = 16) but in the older subjects was 0.60 +/- 0.27 awake and 0.58 +/- 0.34 (NS) asleep (n = 15). The changes from awake to REM in subsets of 9 younger and 10 older subjects who successfully completed REM tests were from 0.95 +/- 0.32 to 0.70 +/- 0.38 (P less than 0.03) and 0.53 +/- 0.31 to 0.57 +/- 0.25 (NS), respectively. We conclude that the increased incidence of respiratory disturbance during sleep in these older subjects cannot be attributed to greater sleep-induced reduction of CO2 sensitivity.

Reverse water-in-fluorocarbon emulsions for use in pressurized metered-dose inhalers containing hydrofluoroalkane propellants.

Pulmonary administration of drugs has demonstrated numerous advantages in the treatment of pulmonary diseases due to direct targeting to the respiratory tract. It enables avoiding the first pass effect, reduces the amount of drugs administered, targets drugs to specific sites and reduces their side effects. Reverse water-in-fluorocarbon (FC) emulsions are potential drug delivery systems for pulmonary administration using pressurized metered-dose inhalers (pMDI). The external phase of these emulsions consists of perfluorooctyl bromide (PFOB, perflubron), whereas their internal phase contains the drugs solubilized or dispersed in water. These emulsions are stabilized by a perfluoroalkylated dimorpholinophosphate (F8H11DMP), i.e. a fluorinated surfactant. This study demonstrates the possibility of delivering a reverse fluorocarbon emulsion via the pulmonary route using a CFC-free pMDI. Two hydrofluoroalkanes (HFAs) (Solkane(R) 134a and Solkane(R) 227) were used as propellants, and various solution (or emulsion)/propellant ratios (1/3, 1/2, 2/3, 1/1, 3/2, 3/1 v/v) were investigated. The insolubility of water (with or without the fluorinated surfactant F8H11DMP) in both HFA 227 and HFA 134a was demonstrated. PFOB and the reverse emulsion were totally soluble or dispersible in all proportions in both propellants. This study demonstrated also that the reverse FC emulsion can be successfully used to deliver caffeine in a homogeneous and reproducible way. The mean diameter of the emulsion water droplets in the pressured canister was investigated immediately after packaging and after 1 week of storage at room temperature. Best results were obtained with emulsion/propellant ratios comprised between 2/3 and 3/2, and with HFA 227 as propellant.

In vivo evaluation of a reverse water-in-fluorocarbon emulsion stabilized with a semifluorinated amphiphile as a drug delivery system through the pulmonary route.

The potential of a reverse water-in-fluorocarbon (w-in-FC) emulsion stabilized with a semifluorinated amphiphile, namely C8F17(CH2)11OP(O)[N(CH2CH2)2O]2 (F8H11DMP) for drug delivery through intrapulmonary administration was investigated in the mouse. This study involved assessment of the effect of single or repeated intranasal instillations of a plain emulsion on lung tissue integrity, and evaluation of blood glucose levels in mice treated with an insulin-loaded emulsion. When instilled intranasally to mice, the plain emulsion did not alter lung tissue integrity, as demonstrated by histological staining, and did not induce any airway inflammatory reaction. Treated mice exhibited decreased body weight within the 3-4 days that followed the first emulsion administration, but this decrease was reversible within few days. Mice instilled intranasally with the insulin-loaded emulsion displayed decreased blood glucose levels within the 20 min that followed the administration, thus demonstrating the potential of the reverse w-in-FC emulsion stabilized with F8H11DMP to systemically deliver drugs, including peptides, upon lung administration.

Neck injuries in frontal impacts: influence of crash pulse characteristics on injury risk.

AIS1 neck injuries are the most frequent disabling injuries among car occupants in road traffic accidents. Although neck injury is mostly regarded as resulting from rear end collisions, almost one third of all neck injuries occur in frontal impacts. The injury mechanisms in both rear-end and frontal impacts are still not known, although different hypotheses exist. Since 1992, approx. 100,000 vehicles on the Swedish market have been equipped with crash recorders to measuring frontal impacts. This paper analyses the influence of different characteristics derived from the acceleration time history on the risk of short- and long-term disability to the neck in frontal impacts. The study includes injury outcomes from 187 restrained front seat occupants in 143 frontal collisions with an overlap exceeding 25%, where the crash pulses have been recorded using crash pulse recorders. The results show that the shape of the crash pulse influences the risk of long-term disability to the neck. The vehicle accelerations in the mid and last third of the crash pulse seem to be important. It is also shown how change of velocity and mean and peak accelerations influence the neck-injury risk. It is suggested that the risk of sustaining an AIS1 neck injury in frontal impacts could be reduced by using more effective pretensioners and more advanced belt-load limiters. These results may also have implications for neck injury mechanisms in rear-end impacts.

How crash severity in rear impacts influences short- and long-term consequences to the neck.

The main public-health problem concerning WAD are injuries leading to long-term consequences. Yet epidemiological studies mostly concentrate on data based on the injury outcome occurring shortly after the crash. The purpose of this article is to study the influence of crash severity in rear impacts leading to short and long-term consequences to the neck (WAD 1-3), lasting less than or more than 1 year. The influence of change of velocity as well as the car acceleration were investigated by using data from crash pulse recorders (CPR) installed in vehicles, involved in rear impacts. The influence of the car acceleration were also investigated by studying the frequency of occurrence of a tow-bar (hinge) on the struck car. Apart from real-life data, full-scale car-to-car crashes were performed to evaluate the influence of a tow-bar on the struck car. The crash tests showed that a tow-bar may significantly affect the acceleration of the car as well as that of the occupant. According to real-life crashes, a tow-bar on the struck car increased the risk of long-term consequences by 22% but did not affect the risk of short-term consequences. Out of the 28 crash recorder-equipped struck cars involving 38 occupants, 15 sustained no injury where the peak acceleration was 6g or less, 20 sustained short-term consequences where the peak acceleration was 10g or less. Three occupants from two different crashes sustained long-term consequences. The two crashes which resulted in long-term disabling neck injuries had the highest peak acceleration (15 and 13 x g), but not the highest change of velocity.

Comparison of car seats in low speed rear-end impacts using the BioRID dummy and the new neck injury criterion (NIC).

Long-term whiplash associated disorders (WAD) 1-3 sustained in low velocity rear-end impacts is the most common disability injury in Sweden. Therefore, to determine neck injury mechanisms and develop methods to measure neck-injury related parameters are of importance for current crash-safety research. A new neck injury criterion (NIC) has previously been proposed and evaluated by means of dummy, human and mathematical rear-impact simulations. So far, the criterion appears to be sensitive to the major car and collision related risk factors for injuries with long-term consequences. To further evaluate the applicability of NIC, four seats were tested according to a recently proposed sled-test procedure. 'Good' as well as 'bad' seats were chosen on the basis of a recently presented disability risk ranking list. The dummy used in the current tests was the Biofidelic Rear Impact Dummy (BioRID). The results of this study showed that NICmax values were generally related to the real-world risk of long-term WAD 1-3. Furthermore, these results suggested that NICmax calculated from sled tests using the BioRID dummy can be used for evaluating the neck injury risk of different car seats.

Longitudinal studies on the interaction of perfluorochemicals with liver cytochromes P-450 by means of testing the rate of detoxification of pentobarbital.

Four perfluorochemicals, Bis-[F-butyl]ethene, perfluorocyclohexylmorpholine, perfluorodecalin and perfluorooctylbromide were compared by their influence on the liver cytochrome P-450 system, measuring the pentobarbital sleeping time as defined by the time of loss of the righting reflex in rats. In all experiments first a prolongation of barbital detoxification was observed, which lasted at least 2-4 days. Thereafter a very long extended period of abbreviated sleeping time followed which was only missed after perfluoroctylbromide. Thus substrate competition, uncoupling of monooxygenation and enzyme induction determine the detoxifying processes in the liver that follow the administration of perfluorochemicals.