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41.
Carsten Olbrich Andrea Gessner Werner Schr?der Oliver Kayser Rainer H Müller 《Journal of controlled release》2004,96(3):425-435
Sleeping sickness is a widely distributed disease in great parts of Africa. It is caused by Trypanosoma brucei gambiense and rhodiense, transmitted by the Tse-Tse fly. After a hemolymphatic stage, the parasites enter the central nervous system where they cannot be reached by hydrophilic drugs. To potentially deliver the hydrophilic antitrypanosomal drug diminazene diaceturate to the brain of infected mice, the drug was formulated as lipid-drug conjugate (LDC) nanoparticles (NP) by combination with stearic- (SA) and oleic acid (OA). To estimate the in vivo compatibility, the particles were incubated with human granulocytes. Because as potential delivery mechanism the absorption of specific serum proteins (ApoE, Apo AI and Apo AIV) was found to be responsible for the delivery of nanoparticles to the brain, demonstrated using PBCA nanoparticles coated with polysorbate 80 (LDL uptake mechanism) the nanoparticles were incubated with mouse serum and the adsorption pattern was determined using the 2-D PAGE technique. As a result of this study, the cytotoxic potential was shown to decrease when diminazene is part of the particle matrix compared to pure fatty acid nanoparticles and the mouse serum protein adsorption pattern differs from the samples studied earlier in human serum. Especially, the fact concerning Apo-E that could be detected when the particles were incubated in human serum is absent after the mouse serum incubation, potentially, is a critical point for the delivery via the LDL-uptake mechanism but the data demonstrate that LDC nanoparticles, with 33% (wt/wt) drug loading capacity possess the potential to act as a delivery system for hydrophilic drugs like diminazene diaceturate and that further studies have to demonstrate the usability as a brain delivery system. 相似文献
42.
43.
Gerhard Koßmehl Andrea Fluthwedel Horst Schfer 《Macromolecular chemistry and physics.》1992,193(1):157-166
Basic materials for contact lenses were obtained by radical copolymerization of linear α,ω-bis(methacryloyloxy)-terminated oligo- and poly(dimethylsiloxane)s, methyl methacrylate and 2,2,3,3,4,4,4-heptafuorobutyl methacrylate. Oxygen permeabilities, contact angles and ball indentation hardness were determined. 相似文献
44.
Massimo Lemma Andrea Mangini Guido Gelpi Andrea Innorta Paolo Danna Francesco Lavarra Emanuela Piccaluga Carlo Antona 《European journal of cardio-thoracic surgery》2003,24(1):81-5; discussion 85
OBJECTIVE: It is not well established whether the blood flow of arterial composite Y-grafts can efficiently respond to the flow demand of the coronary system early postoperatively. The aim of this study was to evaluate if soon after the operation, arterial composite Y-grafts can increase blood flow in response to an increase in myocardial oxygen consumption (MVO2). METHODS: Twenty-seven patients who received complete arterial myocardial revascularization using the left internal thoracic artery (LITA) and the radial artery (RA) as composite Y-graft gave their consent to a pre-discharge coronary angiography and intravascular flow velocity measurements using a Doppler guide wire. Flow measurements were performed in the LITA main stem, the distal LITA and the RA, both at rest and during atrial pacing at the 85% of the patient age-predicted maximum. The heart rate-systolic blood pressure product was considered as an indirect index of MVO2. Hyperemic flow was determined after injection of adenosine. The flow reserve (FR) was defined as the ratio of blood flow during maximal hyperemia (Qmax) to baseline flow (Qbasal). RESULTS: Atrial pacing increased MVO2 significantly (P<0.000). None of the patients developed ischemic S-T segment modifications or complained of chest pain. Q(basal) increased significantly in the LITA main stem (P=0.001), distal LITA (P=0.041) and RA (P=0.004) while Qmax did not change significantly. As a consequence, the FR decreased in the LITA main stem (P=0.002), distal LITA (P<0.000) and RA (P<0.000) but was not completely exhausted. CONCLUSIONS: Soon after the operation, arterial composite Y-grafts can significantly increase blood flow in response to conditions of increased MVO2, keeping normal the myocardial O2 supply-to-demand ratio. 相似文献
45.
46.
Barry W McColl Ailsa L McGregor Andrew Wong Julian D Harris Andrea Amalfitano Sandra Magnoni Andrew H Baker George Dickson Karen Horsburgh 《Journal of cerebral blood flow and metabolism》2007,27(3):477-487
Apolipoprotein E (apoE, protein; APOE, gene) is the major lipid-transport protein in the brain and plays an important role in modulating the outcome and regenerative processes after acute brain injury. The aim of the present study was to determine if gene transfer of the epsilon3 form of APOE improves outcome in a murine model of transient focal cerebral ischaemia. Mice received an intrastriatal injection of vehicle, a second-generation adenoviral vector containing the green fluorescent protein gene (Ad-GFP) or a vector containing the APOE epsilon3 gene (Ad-APOE) 3 days before 60 mins focal ischaemia. Green fluorescent protein expression was observed in cells throughout the striatum and subcortical white matter indicating successful gene transfer and expression. ApoE levels in the brain were significantly increased after Ad-APOE compared with Ad-GFP or vehicle treatment. Ad-APOE treatment reduced the volume of ischaemic damage by 50% compared with Ad-GFP or vehicle treatment (13+/-3 versus 29+/-4 versus 27+/-5 mm(3)). The extent of postischaemic apoE immunoreactivity was enhanced in Ad-APOE compared with Ad-GFP or vehicle treated mice. These results show the ability of APOE gene transfer to markedly improve outcome after cerebral ischaemia and suggest that modulating apoE levels may be a potential strategy in human stroke therapy. 相似文献
47.
Salvatore Serra Giuliana Brunetti Giovanni Vacca Carla Lobina Mauro A M Carai Gian Luigi Gessa Giancarlo Colombo 《Alcohol》2003,29(2):101-108
Results of a recent study have demonstrated that exposure to multiple ethanol concentrations and repeated ethanol deprivation periods in Indiana ethanol-preferring (P) rats resulted in the development of an alcohol deprivation effect (ADE; the temporary increase in voluntary ethanol intake after a period of deprivation from ethanol) characterized by consumption of intoxicating amounts of ethanol. The current study was designed to possibly extend these results to Sardinian alcohol-preferring (sP) rats, generated with the same selective program previously used for P rats. To this aim, ethanol-naive sP rats were exposed initially to the home cage four-bottle choice [10%, 20%, and 30% (vol./vol.) ethanol solutions and water] for eight consecutive weeks. Subsequently, rats were divided into two groups: The first group had continuous access to the four-bottle regimen (nondeprived rats), and the second group was exposed to five cycles of 14-day periods of deprivation from ethanol and 14-day periods of reexposure to the four-bottle regimen. An ADE developed after each deprivation period. However, the extra intake of ethanol was limited to the first hour of each reaccess period. Magnitude of ADE did not change with repeated periods of deprivation. However, a shift in preference toward the two highest concentrations of ethanol solutions was evident from the first reexposure to ethanol and was maintained throughout the study. These results provide further evidence on the heterogeneity of ethanol-drinking behavior among rat lines selectively bred for high ethanol preference and consumption. 相似文献
48.
Marco Cirillo Andrea Amaducci Emmanuel Villa Margherita Dalla Tomba Federico Brunelli Zen Mhagna Giovanni Troise Eugenio Quaini 《Journal of cardiothoracic surgery》2006,1(1):40-11
Background
Long-term morphofunctional outcome may vary widely in surgical anterior left ventricular wall restoration, suggesting variability in post-surgical remodeling similar to that observed following acute myocardial infarction. The aim of this pilot study was to demonstrate that surgical restoration obtained with a particular shape of endoventricular patch leads to steady morphofunctional ventricular improvement when geometry, volume and residual akinesia can be restored as normal as possible. 相似文献49.
Parvalbumin 3 is an Abundant Ca2+ Buffer in Hair Cells 总被引:3,自引:0,他引:3
Stefan Heller Andrea M. Bell Charlotte S. Denis Yong Choe A.J. Hudspeth 《Journal of the Association for Research in Otolaryngology》2002,3(4):488-498
Ca2+ signaling serves distinct purposes in different parts of a hair cell. The Ca2+ concentration in stereocilia regulates
adaptation and, through rapid transduction-channel reclosure, underlies amplification of mechanical signals. In presynaptic
active zones, Ca2+ mediates the exocytotic release of afferent neurotransmitter. At efferent synapses, Ca2+ activates the
K+ channels that dominate the inhibitory postsynaptic potential. A copious supply of diffusible protein buffer isolates the
three signals by restricting the spread of free Ca2+ and limiting the duration of its action. Using cDNA subtraction and a
gene expression assay based on in situ hybridization, we detected abundant expression of mRNAs encoding the Ca2+ buffer parvalbumin
3 in bullfrog saccular and chicken cochlear hair cells. We cloned cDNAs encoding this protein from the corresponding inner-ear
libraries and raised antisera against recombinant bullfrog parvalbumin 3. Immunohistochemical labeling indicated that parvalbumin
3 is a prominent Ca2+-binding protein in the compact, cylindrical hair cells of the bullfrog's sacculus, and occurs as well
in the narrow, peanut-shaped hair cells of that organ. Using quantitative Western blot analysis, we ascertained that the concentration
of parvalbumin 3 in saccular hair cells is approximately 3 mM. Parvalbumin 3 is therefore a significant mobile Ca2+ buffer,
and perhaps the dominant buffer, in many types of hair cell. Moreover, parvalbumin 3 provides an early marker for developing
hair cells in the frog, chicken, and zebrafish. 相似文献
50.
Andrea Sabbadini 《British Journal of Psychotherapy》1991,7(4):406-415
SUMMARY. I have examined the function of silence - its possible role and meanings - in the psychoanalytic encounter. I have argued that silence is complementary to words in general, and to analytic free-associations in particular, and that silence in the patient is often more than just the expression of his resistance.
It could be useful to consider the silent space within a session as a sort of container of words -words that, for complex, over-determined, unconscious reasons cannot be uttered. I have insisted on the significance of analytic silences and warned against responding to them either through a retaliatory silence or through a flood of premature interpretations. These inadequate reactions often stem from the analyst's own anxiety evoked in him by the patient's silence.
Anxiety and silence are closely connected. Each silence is a compromise formation, concealing the unconscious fantasy from which it originates, while expressing a conscious one, often related to the transference situation. It is the task of the analyst to listen to his patient's silences in order to help him understand their meanings. 相似文献
It could be useful to consider the silent space within a session as a sort of container of words -words that, for complex, over-determined, unconscious reasons cannot be uttered. I have insisted on the significance of analytic silences and warned against responding to them either through a retaliatory silence or through a flood of premature interpretations. These inadequate reactions often stem from the analyst's own anxiety evoked in him by the patient's silence.
Anxiety and silence are closely connected. Each silence is a compromise formation, concealing the unconscious fantasy from which it originates, while expressing a conscious one, often related to the transference situation. It is the task of the analyst to listen to his patient's silences in order to help him understand their meanings. 相似文献