[Possible toxicoderma secondary to influenza vaccination].
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Biomedical subjects
Publications and source records attributed to A Grau.
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Iturin A is a lipopeptide extracted from the culture media of Bacillus subtilis which shows a strong antifungal action. The interaction of iturin A with multilamellar vesicles of dimyristoylphosphatidylcholine (DMPC) induced structures which did not sediment during centrifugation. Electron microscopy after negative staining showed that, at 30 mol%, iturin A/DMPC vesicles were visible but smaller than those formed by pure DMPC. Thermograms of DMPC/iturinA obtained after differential scanning calorimetry, at low concentrations of iturin A, were interpreted as indicating the presence of two laterally separated phases, one formed by pure phospholipid and the other by lipopeptide-phospholipid complexes, these two separated phases being already detected even at low concentrations such as 2 mol%. Fluorescence quenching experiments showed that the D-Tyr residue of the lipopeptide was fully accessible to the aqueous medium, indicating that the polar part of iturin A is located outside of the membrane hydrophobic palisade. It was concluded that the membrane barrier properties are likely to be damaged in the area where the lipid complexes are accumulated, due to structural fluctuations, and this may be one of the bases of its biological activity. Iturin-A was also able to greatly destabilize dielaidoylphosphatidylethanolamine (DEPE) membranes in the fluid form, producing a new structure which had a poor correlation in X-ray diffraction, and in 31P NMR spectroscopy gave rise to a spectrum containing a double isotropic signal. Iturin A was shown to induce DEPE to adopt phases other than H(II) inverted hexagonal, underlining that this lipopeptide is capable of modifying the curvature of the membrane, which may also be important in explaining the tendency of iturin A to create small vesicles and which may be another of the bases of its biological activity.
Several variables (kind of filter paper, amount of sample, antioxidant addition, stability of the spectrophotometric measurement, and handling and storage of samples) were found to influence 2-thiobarbituric acid (TBA) values in dark chicken meat when an acid aqueous extraction method with derivative spectrophotometry was used. Filter papers with larger pore diameter or increasing sample weight led to lower TBA values. After incubation of reaction mixtures at 70 degrees C and ice-cooling, tempering for 45 min at room temperature was necessary to stabilize the spectrophotometric measurement. Furthermore, addition of butylated hydroxytoluene (BHT) and ethylenediaminetetraacetic acid disodium salt (EDTA) in the early steps of the method prevented artifactual formation of TBA reactive substances during analysis. Vacuum packaging and storage of samples at -20 degrees C were useful to avoid sample oxidation. The method finally proposed has a coefficient of variation of 3.81 or 4.13% for raw or cooked samples, respectively.
The application of lipid UV absorption (235, 269, and 280 nm) to follow up lipid oxidation in dark chicken meat has been evaluated using raw and cooked samples with different alpha-tocopherol contents (modulated by dietary supplementation). To this purpose, when absorption was measured at 235 nm, second-derivative spectrophotometry did not show any significant advantage over nonderivative spectrophotometry. For absorption at 269 and 280 nm, nonderivative spectrophotometry more sensitively monitored lipid oxidation than second- and third-derivative spectrophotometry. In addition, only direct measurements at 235 and 269 nm and second-derivative measurements at 235 nm showed a limited usefulness to follow up lipid oxidation in our samples. However, these UV absorption parameters were much less effective than lipid hydroperoxide values measured through a ferrous oxidation-xylenol orange method and 2-thiobarbituric acid values determined by a third-derivative spectrophotometric method with acid aqueous extraction.
A ferrous oxidation-xylenol orange (FOX) method was adapted to measure lipid hydroperoxides (LHP) in raw and cooked dark chicken meat. Its applicability was evaluated using samples with different alpha-tocopherol contents or unsaturation degrees (both modulated by dietary supplementation). The FOX assay can work as an induced method because there is some oxidation of the sample extract during the incubation of the reaction. Consequently, it allows assessment of sample susceptibility to oxidation (response after some hours of incubation) and comparison of samples that are highly oxidized or readily susceptible to oxidation through their absorbance after 30 min of incubation. It is highly specific for LHP and showed a linear relationship between volume of meat extract and absorbance. However, the most suitable volume of extract and incubation time must be studied for each kind of sample. The use of butylated hydroxytoluene during this incubation is strongly discouraged because it attenuated the reaction by radical stabilization, thus diminishing Fe(III) formation and leading to a lower response.
BACKGROUND: Recent reports indicated that previous infection may be a risk factor for ischaemic stroke in younger adults and that the increased mortality of cerebrovascular diseases in winter months may be partly caused by the increased rate of infection during the cold season. METHODS: We performed a 1:1 matched case-control study with 197 cases (83 females, 114 males) aged between 22 and 80 years (median age 65 years) to investigate risk factors for acute cerebrovascular ischaemia, in particular the effect of previous infection. We estimated the impact of risk factors in terms of attributable and absolute risks. RESULTS: All risk factors together, previous infection, hypertension, diabetes mellitus, smoking, coronary heart disease, previous stroke or transient ischaemic attack and family history of stroke yield a summary attributable risk of 0.74 [95% confidence intervals (CI) 0.64-0.83]. Recent infections showed a relative risk of 4.3 (95% CI 1.8-10.5) and an attributable risk of 0.15 (95% CI 0.09-0.21). Seventeen percent of the German population are estimated to be in a high-risk group. This subgroup contributes about 55% of the estimated yearly 120,000 incident cases in the age group 55-84 in Germany. DISCUSSION: Identification of high-risk groups for stroke on the basis of individual risk factor distribution and the estimation of its size is possible and may produce useful results. Reducing the prevalence of infection and early treatment of bacterial infection may lower the incidence of stroke.
Surfactin, an acidic lipopeptide produced by various strains of Bacillus subtilis, behaves as a very powerful biosurfactant and posses several other interesting biological activities. By means of differential scanning calorimetry and X-ray diffraction the effect of surfactin on the phase transition properties of bilayers composed of different phospholipids, including lipids forming hexagonal-HII phases, has been studied. The interactions of surfactin with phosphatidylcholine and phosphatidylglycerol seem to be optimal in the case of myristoyl acyl chains, which have a similar length to the surfactin hydrocarbon tail. Data are shown that support formation of complexes of surfactin with phospholipids. The ionized form of surfactin seems to be more deeply inserted into negatively charged bilayers when Ca2+ is present, also supporting the formation of surfactin-Ca2+ complexes. In mixtures with dielaidoylphosphatidylethanolamine, a hexagonal-HII phase forming lipid, surfactin displays a bilayer stabilizing effect. Our results are compatible with the marked amphiphilic nature of surfactin and may contribute to explain some of its interesting biological actions; for instance the formation of ion-conducting pores in membranes.
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The purpose of this study was to demonstrate selective visualization of pulmonary arteries and veins with high spatial resolution for improved detection of vascular pathologies. Time-resolved pulmonary three-dimensional gadolinium-enhanced magnetic resonance angiograms (3D-Gd-MRA) were acquired with an ultrashort 3D fast low-angle shot (FLASH) sequence (TR/TE 2.3/0.9 msec) using asymmetric k-space sampling in readout, phase-encoding, and partition directions. In a single breath-hold four consecutive acquisitions were performed with a scan time of 6.28 seconds for each phase. A spatial resolution of 1.9 x 1.4 x 2 mm(3) could be achieved for a 12 cm thick 3D volume. To exploit the intrinsic enhancement kinetics of the pulmonary vascular system, the infusion of two gadolinium chelate boli was synchronized with the acquisition of the first and third data sets. This infusion strategy created two predominantly pulmonary arterial and venous data sets with the arterial and venous signal being maximally anti-correlated in time. A further separation of arterial and venous signal could be achieved by means of a correlation analysis. Eight patients with suspected thrombi in the pulmonary veins were studied. The calculated correlation angiographies provided high-quality pulmonary arterio- and venograms. Background signal was completely eliminated, allowing maximum intensity projection analysis of the full data set. In 7/8 patients no venous contamination of the arterial phase and vice versa was found. Patency of the pulmonary arteries and veins could be reliably assessed to the level of the segmental vessels. The combination of ultrafast multiphase 3D-Gd-MRA and dual-bolus injection with a correlation analysis of vascular signal provides high-resolution pulmonary arterio- and venograms. This imaging strategy initiates a new competitor to X-ray angiography.
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The cause of spontaneous cervicocerebral artery dissection is unknown. An underlying arteriopathy due to a connective tissue disorder has often been presumed. We studied 25 patients with proven nontraumatic dissections. The ultrastructural morphology of dermal connective tissue components was assessed by transmission electron microscopy of skin biopsies. Ultrastructural abnormalities were seen in 17 (68%) patients, resembling in some cases the aberrations found in Ehlers-Danlos syndrome type II or III. These observations indicate a correlation of cervical artery dissections with connective tissue abnormalities. A structural abnormality in the extracellular matrix potentially caused by basic molecular defects is suggested and warrants further exploration.
AIM: Improved detection of pulmonary-venous pathologies by imaging the pulmonary veins without arterial overlay. MATERIAL AND METHODS: Sequential 3D imaging of the pulmonary arterial and arteriovenous phase was performed with an ultrafast 3D FLASH sequence successively acquiring eight 3D data sets every 2.9 s within a single breathhold. For an 8 cm thick 3D slab an interpolated spatial resolution of about 1.4 x 1.9 x 3.3 mm could be achieved. Different protocols for contrast media dose and infusion rate were used. For selective visualization of the pulmonary veins, the pulmonary arterial phase was subtracted from a subsequent arteriovenous phase with the highest venous signal. 5 healthy volunteers, 8 patients with history of a cerebrovascular accident (CVA) of unknown etiology an suspected pulmonary-venous thrombosis and 9 patients with compression of the pulmonary vasculature by centrally growing malignancies were evaluated. RESULTS: With higher infusion rate and lower contrast media dose, arteries and veins could be better separated by their enhancement kinetics. In all cases a complete visualization of the main pulmonary veins, segmental and subsegmental veins up to the fourth order of each lung segment was achieved without any overlay of pulmonary arteries. No thrombi of the pulmonary veins were found in patients with CVA. The obstruction of pulmonary arteries and veins due to vessel compression could be selectively visualized. CONCLUSION: Ultrafast multiphase 3D-Gd-MRA is a new reliable method for selective 3D visualization of pulmonary veins.
Recent studies have shown that acute infections, especially of the respiratory tract, are an important risk factor for cerebral ischemia. Additionally we know that chronic dental infections may be a risk for myocardial infarction and artherosclerosis. However, the connection between stroke and dental infections has hardly been examined so far. Therefore we performed a case-control study using a standardized questionaire and examination. We investigated 66 patients consecutive to a acute cerebral ischemia/stroke and 60 age- and sex-matched nonstroke neurological patients as a control group. Dental status was determined by a so called total dental index (TDI) which reflects primarily caries, periodontitis, periapical lesions, devital and missing teeth as well as by a panoramic index (PI). Specifically, older patients with cerebrovascular ischemia tended to have a significantly worse dental status and had more severe periodontitis and periapical lesions than control subjects. A predefined poor dental status was associated with cerebrovascular ischemia independent from other vascular risk factors and social status. In conclusion, poor dental health, mainly resulting from chronic dental infections, may be associated with an increased risk for cerebrovascular ischemia. The results must now be verified in larger studies. As chronic dental infections are a common and also easily treatable factor, their identification as a risk factor for stroke would be quite important in the field of preventive medicine.
Porcine pancreatic phospholipase A2 (PLA2) hydrolyses phosphatidylcholine when in the lamellar state as well as in the micellar state. We have found that alpha-tocopherol, the most active form of vitamin E, is able to inhibit PLA2 activity only toward lamellar fluid membranes, thus protecting phospholipids toward this lytic enzyme. This compound decreases both the initial rate and the extent of hydrolysis. The inhibition is of the non-competitive type and the evidence strongly suggests that it is due to an effect of alpha-tocopherol on the substrate, i.e. the membrane, and not on the enzyme itself. Other tocopherols, such as the isomers beta-, gamma- and delta-tocopherol also display PLA2 inhibition but consecutively to a lower extent. The grade of inhibition of PLA2 activity by tocopherols correlates well with their biological activity and with their location in the bilayer as shown by fluorescence quenching. Cholesterol does not inhibit PLA2 activity at concentrations even higher than those of tocopherols, indicating that the effect of tocopherols is not due to alteration of membrane fluidity. The possible mechanisms underlying the different behaviour of tocopherol isomers as PLA2 inhibitors are discussed considering its biological significance as membrane stabilizers, suggesting biological actions of compounds with vitamin E activity other than their classical roles as antioxidants.
BACKGROUND AND PURPOSE: It has been recently reported that a G-->A transition at nucleotide position 20210 in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of deep venous thrombosis. To date, it is unknown whether this polymorphism also represents a risk factor for cerebral venous thrombosis (CVT). METHODS: Venous blood samples were collected from 45 patients with CVT and from 354 healthy blood donors as controls. A second control group consisted of 131 subjects with acute ischemic stroke or transient ischemic attack (TIA). Genomic DNA was isolated from peripheral blood leukocytes. Amplification of DNA was performed by polymerase chain reaction (PCR). The G-->A transition at nucleotide position 20210 of the prothrombin gene was detected by allele-specific restriction digestion. RESULTS: The G20210-->A transition in the prothrombin gene was found in a heterozygous form in 4 of 45 patients with CVT (8.9%) and in 8 of 354 healthy control subjects (2.3%). This difference was statistically significant (P=0.010). The G20210-->A transition increased the relative risk for CVT approximately 5-fold (age-adjusted odds ratio 5.7; 95% CI 1.5 to 21.5). In contrast, in the group of patients with acute cerebral ischemia, only 3 of 131 subjects (2.3%) were heterozygous for the G20210-->A transition, which corresponded to the prevalence in the group of healthy blood donors. CONCLUSIONS: The recently described G20210-->A transition in the 3'-untranslated region of the prothrombin gene is an inherited risk factor for CVT but obviously not for acute ischemic stroke or TIA.
Tay-Sachs disease is a genetically determined neurodegenerative disorder, resulting from mutations of the hexosaminidase (Hex) A gene coding for the alpha-subunit of beta-D-N-acetyl-hexosaminidase. Clinically, there is severe encephalomyelopathy leading to death within the first few years of life. Hex A activity is usually absent in tissue and body fluids of these patients. Juvenile and adult Hex A deficiencies are less severe but rare variants with some residual Hex A activity. All these variants are most prevalent among Ashkenazi Jews. We describe a non-Jewish family in which four adult brothers and sisters had markedly reduced Hex A activities and onset of symptoms in the second decade of life. The phenotypical expression was remarkably homogeneous, consisting in a combination of slowly progressive motor neuron disease, ataxia and ocular motor disturbances. None of the patients were demented at this stage of their illness. Magnetic resonance studies showed severe cerebellar atrophy, but were otherwise normal. Hex A deficiency was established by biochemical measurements in the serum and skin fibroblasts using the fluorogenic substrates 4-MUG and 4-MUGS as well as by gel electrophoresis. Molecular genetic studies revealed that the patients are compound heterozygotes for the 'adult' mutation Gly269 --> Ser and the 'infantile' 4-base insertion in exon 11 of the Hex A gene.
Treatment strategies for acute ischemic stroke include general and specific measures. The rationale for these strategies is discussed, and the current practice in the acute phase of ischemic stroke is presented. Special attention is given to the patient requiring intensive care.
The third case in the literature is reported of an infection produced by Pleistophora. The clinical detail of the three cases are discussed. Two of the patients-including the reported one-were infected by HIV. All patients suffered from myositis with fever, resting and at palpation myalgia, and progressive weakness. Blood tests showed anaemia and high levels of muscle enzymes. Necrotic muscle fibrosis induced disabling contractures. Diagnosis was obtained by detecting the protozoon in a muscle biopsy. The spores may be detectable by means of different staining methods at light microscopy although electron microscopy remains the most reliable technique. Since this is such a rare condition there is no known treatment. Whether the albendazole could be as useful as occurs in patients infected by other genera of microsporidia in still uncertain.