Biomedical subjects

J Steibel

Publications and source records attributed to J Steibel.

18 recordsLinked to original sources

PubMed2001

High antigenicity of intraperitoneal insulin infusion via implantable devices: preliminary rat studies.

Intraperitoneal insulin infusion of Genapol stabilized insulin via implantable devices significantly improves diabetes control and hypoglycemia frequency in type 1 diabetes while it increases insulin antibody levels. Causes for this particular antigenicity remain unknown. The role of insulin modifications occurring in the reservoir on the antigenicity observed was assessed by comparing the antigenicities of the insulin coming from the vial or from the pump reservoir. Rats were injected intraperitoneally with insulin sampled either from a vial (group 1) or from a pump reservoir during a refill of a clinical trial (group 2). Two control groups, one without insulin, the second one receiving a mixture of silicone and insulin were also studied. Human insulin antibody levels were assessed by RIA 10 days after 4 weekly immunizations. AIA levels were higher in group 1 compared to group 2 (P = 0.003 for the first experiment, P = 0.04 in the second experiment). The increased antigenicity of the insulin sampled from the implanted pump might be due to the insulin modifications occurring during the storage in the device. Insulin aggregates could be involved in this antigenicity since they are known to be antigenic and their concentration was shown to be related to the amplitude of the antigenic response.

Animals↗

PubMed2000

Antibody directed against mannan of the Mycobacterium tuberculosis cell envelope provokes blood-brain barrier breakdown.

Previous studies demonstrated that blood-brain barrier (BBB) breakdown observed at the cerebral level during experimental allergic encephalomyelitis (EAE) arises from the presence of Mycobacterium tuberculosis in Freund's adjuvant and not only from the encephalitogenic antigens. The main objective of this study was to check if the mannan moiety of lipoarabinomannan present in the mycobacterial cell envelope is responsible for an immune response provoking a BBB breakdown. The results showed that: firstly, the complete Freund's adjuvant (CFA) contains a high release of polysaccharides; secondly, the rats immunized with the CFA present important serum concentration of anti-mannan antibody; and finally, a single 2-mg dose of anti-mannan antibody injected intravenously in naive rats provokes an immediate and reversible BBB breakdown. These results suggest that mannan arising from the solubilization of the mycobacterial cell wall in Freund's adjuvant induces a high production of anti-mannan antibody, which, in turn, provokes a BBB breakdown and possibly facilitates the induction of EAE.

Animals↗

PubMed2000

In vivo 129Xe NMR in rat brain during intra-arterial injection of hyperpolarized 129Xe dissolved in a lipid emulsion.

Hyperpolarized 129Xe was dissolved in a lipid emulsion and administered to anaesthetized rats by manual injections into the carotid (approximately 1-1.5 mL in a maximum time of 30 s). During injection, 129Xe NMR brain spectra at 2.35 T were recorded over 51 s, with a repetition time of 253 ms. Two peaks assigned to dissolved 129Xe were observed (the larger at 194 +/- 1 ppm assigned to intravascular xenon and the smaller at 199 +/- 1 ppm to xenon dissolved in the brain tissue). Their kinetics revealed a rapid intensity increase, followed by a plateau (approximately 15 s duration) and then a decrease over 5 s. This behaviour was attributed to combined influences of the T1 relaxation of the tracer, of radiofrequency sampling, and of the tracer perfusion rate in rat brain. Similar kinetics were observed in experiments carried out on a simple micro-vessel phantom. An identical experimental set-up was used to acquire a series of 2D projection 129Xe images on the phantom and the rat brain.

Animals↗

PubMed1999

NMR studies in demyelinating and non-demyelinating experimental allergic encephalomyelitis. An approach involving a dehydration procedure.

The spinal cords of rats, involved as part of two distinct and reproducible experimental allergic encephalomyelitis animal models, presenting inflammatory white matter lesions with and without demyelination, were studied in vitro by NMR, before and after a dehydration procedure, in order to characterize demyelination. All the parameters of the T1 and T2 relaxation times were determined, as well as the initial proportion of the very quickly decaying component of the free induction decay, and the magnetization transfer ratio. The relaxation decays were fitted with the discrete and Contin methods. Magnetization transfer ratio measurements permitted first to evaluate the magnetization transfer at the apex, and secondly to decompose the post-irradiation curves into two components: a gaussian and a lorentzian line, with their relative proportions and widths. The results presented in this study clearly demonstrate that it is not possible to evidence demyelination in fresh spinal cord preparations by NMR. However, the dehydration procedure, which was introduced with the aim of reducing the amount of free water in our samples, seems sufficient to enable the detection of demyelination from the T2 relaxation spectra and magnetization transfer data. As a conclusion, we think that the NMR properties of water protons allow to achieve tissue characterization on condition that the parameters concerning free water and its exchanges are eliminated.

Animals↗

PubMed1998

Magnetic resonance imaging of PLP-induced experimental allergic encephalomyelitis in Lewis rats.

An in vivo magnetic resonance (MR) imaging study was performed on experimental allergic encephalomyelitis (EAE) induced in Lewis rats through proteolipid protein (PLP). PLP was solubilized in water or in an aqueous solution of 1% 10-tridecyl ether (TDE), a non-ionic detergent used in membrane protein research. All 16 rats immunized with 500 microg of TDE-solubilized PLP developed clinical signs and MR abnormalities fully comparable to those observed in MBP-induced EAE. Total paraplegia was observed in 12.5% of rats, mild or moderate paraparesis in 68.8% of rats and tail paralysis in the remaining 18.7% of rats. Whereas only 37.5% of the eight rats immunized with 500 microg of water-solubilized PLP developed minor clinical signs (tail weakness or paralysis). Our observations confirm that the difficulties encountered when trying to induce EAE by means of PLP arise from the highly hydrophobic nature of this protein. Accordingly, if a reproducible model is to be developed, it seems more judicious to use non-ionic detergents in both the extraction and solubilization phases of PLP preparation, this would allow maximal solubilization of the protein while avoiding aggregates, which may otherwise form during either of the PLP preparation.

Animals↗

PubMed1994

Localized T2 measurements using an OSIRIS-CPMG method. Application to measurements of blood oxygenation and transverse relaxation free of diffusion effect.

This work presents a new method allowing localized T2 measurements, based upon the OSIRIS scheme. A train of 180 degrees pulses is applied after the OSIRIS preparation cycle, recording directly the transverse magnetization decay. The method was verified for two nuclei, 1H and 19F, with phantoms and in vivo on rats. The accuracy of the T2 values is discussed, as well as possible applications of the OSIRIS-CPMG method to proton transverse spin relaxation measurements, free of diffusion effects, and to non-invasive in vivo blood oxygenation measurements, through the use of an emulsion of perfluorooctylbromide, a blood substitute containing fluorine.

Animals↗

PubMed1994

Hyperbaric oxygen treatment in acute experimental allergic encephalomyelitis. Contribution of magnetic resonance imaging study.

Magnetic resonance imaging (MRI) has been performed to determine the efficacy of hyperbaric oxygen treatment (HBO) on experimental allergic encephalomyelitis (EAE) in Lewis rats. The animals were exposed for 2 x 3 h in a 24-h period at 2 ATA pure O2. Three HBO treatment protocols were used: a 10-day preventive treatment (beginning on the 1st day postimmunization), a 3-day preventive treatment (beginning on the 1st day postimmunization), and a 10-day symptomatic treatment (beginning on the 11th day postimmunization). Based on clinical and MRI observations, this study demonstrates: (i) that HBO treatment does not reduce the blood-brain barrier (BBB) disturbance and cerebral edema in EAE, (ii) that in an opposite way, it provokes reversible BBB breakdown, and (iii) that preventive HBO treatments results in modification of the course of EAE, possibly by immunosuppression effect during the initial sensitization step.

Animals↗

PubMed1994

Magnetic resonance imaging of antibody-mediated demyelinating experimental allergic encephalomyelitis.

Two models of demyelinating experimental allergic encephalomyelitis (EAE) were studied on Lewis rats in whom the disease was induced by injections of either (i) lentil-lectin binding myelin glycoproteins plus myelin basic protein (MBP)-specific T cells (36 rats), or (ii) myelin/oligodendrocyte glycoprotein-specific monoclonal antibody plus MBP-specific T cells (16 rats). In our 24 control rats, 20 received MBP-specific T cells only, and four received myelin glycoproteins plus purified protein derivative-specific T cells. The extent of the resulting blood-brain barrier (BBB) permeability, vasogenic oedema and/or demyelination was assessed in vivo using magnetic resonance imaging (MRI) techniques. The results show that in both demyelinating EAE models the disease appeared more quickly, progressed very rapidly and was more severe than when induced with a similar number of MBP-specific T cells alone. Almost all animals developed hyperacute EAE, with a very high mortality rate. MRI showed a very intense BBB breakdown and vasogenic oedema in all the normally 'leaky' areas of the central nervous system, and focal lesions corresponding to plaque formation in the brain stem or spinal cord near the 'leaky' areas. During the 40-day observation period, the rare survivors of this hyperacute form of EAE presented a chronic form of EAE with serious sequelae. Our results demonstrate that the synergistic effect observed between MBP-specific T cells and antibodies to myelin glycoproteins, especially to myelin/oligodendrocyte glycoprotein, does not only induce demyelinating lesions and chronic clinical signs, but is further responsible, via the normally 'leaky areas', for the fatal increase of the BBB breakdown and vasogenic oedema of which there are ample acute clinical signs.

Animals↗

PubMed1994

The role of Mycobacterium tuberculosis in experimental allergic encephalomyelitis.

Various detergents used in preparative membrane protein chemistry were added to a complete Freund's adjuvant/water emulsion in order to increase the solubility and/or immunologic availability of the Mycobacterium tuberculosis membrane and to explain its role in blood-brain barrier (BBB) permeability. Magnetic resonance imaging was used for in vivo determination of the BBB breakdown and cerebral edema. The results showed that with 1% 10 tridecyl ether, which increases emulsion stability, abundant BBB breakdown and cerebral edema were observed, similar to those encountered in experimental allergic encephalomyelitis (EAE). We suggest that the immunologic response triggered off by M. tuberculosis largely contributes to the BBB permeability changes observed during EAE, probably by an action on the endothelial cells of the cerebral blood vessels.

Animals↗

PubMed1994

[Magnetic Resonance Imaging study of the role of the blood-brain barrier in the pathogenesis of experimental allergic encephalomyelitis: application to multiple sclerosis].

Nuclear magnetic resonance imaging (MRI) proved to be, from the first, a very sensitive method, allowing the visualisation of multiple sclerosis lesions, yet which never permitted to establish a non equivocal relationship between the semeiology of such lesions and the clinical signs. The multifocal aspect of disseminated multiple sclerosis lesions is probably one of several factors accounting for this discrepancy. The study of an autoimmune disease, experimental allergic encephalomyelitis (EAE), regarded as a suitable model for multiple sclerosis in humans, has been performed using MRI in order to unravel the pathogenesis of the disease and apprehend the mechanisms responsible for the formation of multiple sclerosis lesions. The study focused on the part played by the blood-brain barrier (BBB) in the induction process of an autoimmune disease, since the central nervous system is normally screened from immunological supervision, by this barrier. Models both of acute EAE, induced by active or passive transfer of the antigen (myelin basic protein-MBP)--and chronic EAE, induced by passive transfer of MBP-specific T cells and myelin glycoproteins or MOG-specific monoclonal antibodies, have been reproduced, and their evolution followed up using high field MRI. Every time, the crucial role of the BBB was evidenced by the synchronism existing between the clinical signs, the appearance of lesions, preferentially in the most sensitive or permeable areas, and the BBB breakdown encouraged by the action of adjuvants. The physiopathological study of EAE using MRI is suggestive of the concept of systemic disease for multiple sclerosis, according to a two-step process, involving, in a first stage some primary viral or bacterial infection, causing T-cells to be sensitized to the host's own proteins by molecular mimicry, and in a second stage some bacterial infection or accidental circumstances which, resulting in a BBB breakdown, would provide immunocompetent cells with an opportunity to reach their target.

Animals↗

PubMed1993

Blood-brain barrier breakdown in MBP-specific T cell induced experimental allergic encephalomyelitis. A quantitative in vivo MRI study.

Blood--brain barrier permeability in myelin basic protein (MBP)-specific T cell induced experimental allergic encephalomyelitis (EAE) was studied by magnetic resonance imaging (MRI) in Lewis rats. Myelin basic protein-specific T cells of different specificity and/or purified protein derivative (PPD)-specific T cells were used. During the course of EAE, the volume of the lesions and the T1 and T2 relaxation times were recorded and evaluated with respect to the clinical signs. The results showed that the severity of abnormalities seen on MRI, corresponding to the blood--brain barrier breakdown and cerebral oedema depended on the following two factors: (i) the specificity of the MBP-specific T cells used; (ii) the number of MBP-specific T cells transferred. It was also shown that the more specific the cells were, the less severe the cerebral blood--brain barrier rupture. Moreover, the blood--brain barrier breakdown increased when the number of cells increased. Our results demonstrated that a synergy exists between MBP and PPD-specific T cells which seems to result in an increase in central nervous system inflammation. This helps to explain the role of Mycobacterium tuberculosis in the induction of EAE.

Animals↗

PubMed1992

In vivo dynamic MR imaging of MBP-induced acute experimental allergic encephalomyelitis in Lewis rat.

A dynamic in vivo study by MRI consisting of the measurement of relaxation times and in the visualization of the BBB permeability by Gd-DOTA was performed in an MBP-induced acute EAE model of Lewis rat. Fourteen rats were immunized with an MBP/CFA mixture, eight by CFA alone, and three control rats were used to test the harmless effect of repeatedly performed MRI examinations. Beginning on the 8th or 9th days and in parallel with the emergence of clinical signs, rats immunized by the MBP/CFA mixture showed slight increases of relaxation times and of the BBB permeability. These abnormalities, which always remain localized in the periventricular regions, become more pronounced toward the 10th and 11th days, just before (or at the same time) as paraplegia manifestations. After a plateau of a few days, they diminish with the clinical signs. This close correlation found in vivo establishes the essential role of BBB in the pathogenesis of clinical signs of this EAE model.

Animals↗

PubMed1986

Chemical and molecular exchange effects on T2 relaxation of living tissues: a pulse spacing dependence study.

Contrast in magnetic resonance imaging depends principally on the longitudinal relaxation (R1) and the transverse relaxation rate (R2) of the observed nuclei, most often the protons. The spin-spin relaxation rate (R2) is the result of several mechanisms. The dependence of the interpulse delay of the Carr-Purcell-Meiboom-Gill sequence on the transverse relaxation rate of the water was studied in rat organs in vitro. It gives an insight into the exchange mechanisms involved. The increase of the interpulse delay from 0.2 ms to 5 ms gives an R2 increase of 23, 15, 3, and 2 s-1 for the heart, the liver, the spleen and the brain, respectively. These increases are compared to the R2 increases obtained in 17O-enriched water, amino acid and albumin solutions atomic exchange takes place. The concentration of these materials in organs cannot explain the R2 increase of the organs with the interpulse delay. Water exchange between intra and extracellular compartments is proposed to explain the R2 increase with interpulse delays in organs like the heart and the liver.

Albumins↗

PubMedDate not supplied

Localized T1 measurements using an inversion-recovery OSIRIS method.

This work presents a new method for localized T1 measurements, based upon the OSIRIS scheme. It relies on the use of a non-selective 180 degrees pulse applied before the OSIRIS preparation cycle. The accuracy of the method has been verified with test tubes and in vivo for two nuclei, 1H and 19F. The accuracy of the T1 values is discussed, as well as possible applications of the inversion-recovery method to non-invasive in vivo pO2 measurements.

Animals↗

PubMedDate not supplied

Susceptibility-based MRI contrast of the CSF by intravascular superparamagnetic nanoparticles.

Endorem, a suspension of superparamagnetic iron oxide dextran nanoparticles (NP), have been injected intravenously to healthy anesthetized rats for the purpose of contrast enhancement of brain in gradient-echo imaging at 200 MHz. Not only gray and white matter but also particular regions of the cerebrospinal fluid (CSF) were contrasted in sagittal and transverse images, although samples of this fluid did not contain NP. The selected contrast in the CSF would result form the ability of dense vascular beds containing highly magnetized particles to induce a remote susceptibility effect far beyond the vascular walls into a large fraction of extravascular water.

Animals↗

PubMedDate not supplied

[Periodontal disease in pregnancy and low birth weight]

OBJECTIVE: Recently, it has been suggested that periodontal disease during pregnancy could have a causal relationship with low weight at birth. Our objective was to evaluate the influence of periodontal disease during pregnancy on the birth weight of newborn infants. METHODS: Mothers who gave birth to low-birth-weight infants were randomly selected (Group 1 - G1; n=13). Immediately after inclusion of each mother in group 1, the mother of the next term newborn with birth weight of > 2,500 g (Group 2 - G2; n=13) was included as control. Mothers were examined by a periodontist who was not informed of the group the child belonged to. A probe was used to measure attachment loss of the alveolar bone. The extension index (EI) and severity index (SI) of the periodontal disease were determined. RESULTS: Both groups of mothers were similar in terms of maternal age, parity, color of skin, height, nutrition, smoking, drinking, socioeconomic status, prenatal examinations, premature rupture of membranes, chorioamnionitis, bacteriuria, placenta previa, abruptio placentae, previous hypertensive disease, preeclampsia, and heart disease. The characteristics of the newborns were: birth weight - G1 = 1,804 -/+ 675 g x G2 = 3,030 -/+ 516 g; gestational age - G1 = 33 -/+ 5 weeks x G2 = 39 -/+ 2 weeks; length of stay in the neonatal intensive care unit (NICU) - G1 = 128 days x G2 = 0 days. Average EI: G1 = 89.788 -/+ 18.355 x G2 = 72.420 -/+ 20.717; p=0.033. Average SI: G1 = 1.377 -/+ 0.626 x G2 = 0.754 -/+ 0.413 (OR=18.3; CI95%: 2.5-133.3; p = 0.006). After adjustment for risk factors for low birth weight, such as smoking, maternal height, bacteriuria, and previous hypertension, the odds ratio for SI dropped to 7.2 (CI95% = 0.4-125.4; P = 0.176). CONCLUSION: The multivariate analysis indicated a marked association between periodontal disease measured by SI score and low birth weight. Our data suggested that periodontal disease during pregnancy may be a risk factor for low weight at birth.

Journal Article↗

PubMedDate not supplied

31P NMR spectroscopy of photodynamically treated cells.

The metabolic response of Chinese Hamster Ovary (CHO) cells during photodynamic therapy (PDT) with hematoporphyrin IX (Hp IX) and pheophorbide (Ph) was monitored in real time by 31-phosphorous (31P) nuclear magnetic resonance (NMR) spectroscopy. The effects of the delivered light dose and of cell oxygenation were investigated. A delayed disappearance of nucleoside triphosphate (NTP) following irradiation was observed, which was related to the treatment efficiency. For cells irradiated with a light dose of 0.8 J/cm2 in the presence of Hp IX, the disappearance of the NTP peaks occurred within 30 minutes of irradiation, but for an irradiation of 0.24 J/cm2, the disappearance of the NTP peaks occurred about 6 hours later, and this delayed disappearance is related to the surviving fraction. For irradiation experiments involving Ph and a light dose of 0.036 J/cm2, NTP in injured cells began to decrease about 3 hours after irradiation, whereas for a light dose of 0.24 J/cm2, we observed the instantaneous disappearance of the NTP peaks occurring during the irradiation time. The same efficiency was obtained with two different oxygen partial pressures in the perfusate (360 and 154 mmHg) and a light dose of 0.24 J/cm2.

Animals↗

PubMedDate not supplied

Experimental observation of photochemically induced oxygen depletion in perfused cells undergoing photodynamic therapy.

This report presents a non invasive method for studying oxygen consumption during photodynamic therapy in cultured cells. The oxygen partial pressure of perfusion medium flowing through cells cultured on microcarrier beads, was investigated before, during and after treatment. Pheophorbide a was used as a sensitiser. Time-dependent measurements demonstrate photochemical oxygen depletion induced by photosensitized reactions, followed by an oxygen pressure increase were attributed to a reduction in the cells' metabolism.

Animals↗