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91.
Despite early diagnosis and treatment, 35% of the patients with glutaric aciduria type I (GA I) develop severe neurologic damage. Glutaric acid and 3-hydroxyglutaric acid have been suspected to cause neurodegeneration. Lately, this has been questioned, however. We postulate that glutaconyl Coenzyme A (glutaconyl-CoA) is responsible for brain damage. Chemically, glutaconyl-CoA is an analogue of acrylyl-CoA, the parent substance of the extremely reactive class of acrylates. It is expected to react spontaneously with sulfhydryl groups, thus modifying membranes, disturbing enzyme functions and trapping glutathione. Enhanced production of glutaconyl-CoA together with lack of glutathione precipitates brain damage. Such a mechanism is supported by three findings. (1) The addition product of glutaconyl-CoA to cysteine is present in small amounts in normal human urine. (2) Reaction of methacrylyl-CoA with free sulfhydryl groups has been reported previously in a patient with 3-hydroxyisobutyryl CoA deacylase deficiency. (3) Glutathione has been found to be decreased in homozygous glutaryl-CoA dehydrogenase-deficient knock-out mice. 相似文献
92.
Jan E. de Vries John Mendelsohn Willy S. Bont 《International journal of cancer. Journal international du cancer》1980,25(1):73-84
Lymphocytes from 12 healthy donors were depleted of monocytes by velocity sedimentation at unit gravity (average monocyte contamination 0.2%) and tested for spontaneous cytotoxicity (SC) against tumor target cells in 24 h microcytotoxicity assays. Sixty percent of all lymphocytes were recovered in this monocyte-de-pleted lymphocyte fraction (LF). In contrast, with the corresponding unfractionated lymphocytes (UL) the LF cells were not spontaneously cytotoxic on T24 bladder carcinoma, NKI-1, NKI-7, NKI-8, NKI-1O melanoma, and MC-1 mammary carcinoma cell line cells and target cells derived from two short-term melanoma cultures (Me 215 and Me 223). SC of the LF could be restored by reconstitution with autologous monocytes, which were obtained >80% pure in the same velocity sedimentation procedure. Addition of 4–8% monocytes was sufficient to restore the SC of the LF to the level achieved with the corresponding UL, whereas maximal induction of SC was observed after addition of 8–16% monocytes. Higher numbers of monocytes had suboptimal effects. SC of the LF could also be restored by monocyte culture supernatants. The spontaneous cytotoxic effector cells were characterized as non-E rosette-forming, membrane slg-negative Fc-receptor-bearing lymphocytes, a proportion of which probably also bear C3-receptors. Since the LF was not spontaneously cytotoxic, in spite of the presence of Fc-receptor bearing lymphocytes, it is concluded that monocyte help, mediated via soluble factors, is required. Evidence is presented that the lack of SC by the LF might be attributable to the failure of these cells to make appropriate contact with the target cells. LF/target cell contact followed by target cell kill occurred after addition of monocytes. Effector/target cell contacts, artificially established by agglutinins, did not result in target cell kill. Thus the effector/target cell contacts observed in the presence of monocytes suggest recognition of particular membrane determinants involved in SC. An identical requirement for monocytes was observed with LF cells from 5 stage I and 5 stage II melanoma patients tested for SC against both melanoma and non-melanoma target cells. This indicates that either the cytotoxicity against melanoma cells with lymphocytes from melanoma patients is of the same nature as the SC of lymphocytes from healthy donors, or that specific melanoma-associated cellular cytotoxicity also requires monocyte help. 相似文献
93.
Malaisse WJ 《International journal of molecular medicine》2005,15(2):243-246
The non-invasive imaging of the endocrine pancreas is currently considered by concerned institutions as a priority theme of research. Because the endocrine pancreas represents only about one percent of the pancreatic gland, highly specific tools are required for labelling the insulin-producing cells. The present review deals with the possible use of D-mannoheptulose for the non-invasive quantification of insulin-producing cells in the pancreas. This heptose is transported into hepatocytes and insulin-producing cells, but not other cell types, at the intervention of GLUT2. Its uptake coincides with the intracellular accumulation of acidic metabolites generated by phosphorylation of D-mannoheptulose. These metabolites remain in the islet cells after prolonged washing, suggesting that imaging of the pancreas at a relatively late time after intravenous administration of D-mannoheptulose could avoid significant extracellular contamination. Using tritiated D-mannoheptulose as tracer, a new method was designed for quantification of the total mass of insulin-producing cells in either isolated perfused rat pancreata or isolated pancreatic islets. Likewise, a preferential labelling of hepatocytes and insulin-producing transplanted cells can be achieved in vivo after administration of tritiated D-mannoheptulose. In the light of results obtained with 6-deoxy-6-iodo-D-glucose, it is proposed that 7-deoxy-7-iodo-D-mannoheptulose could be used for the non-invasive imaging of the endocrine pancreas. 相似文献
94.
95.
OBJECTIVES: We sought to review and describe the practice of electroconvulsive therapy (ECT) in Flanders and the Brussels Capital region, Belgium, in 2003. METHODS: A 30-item questionnaire was sent to all institutions that provided psychiatric care. Besides questions on training and general attitude toward ECT, most questions concerned technical aspects, quality, and organization of this treatment modality. RESULTS: All psychiatric departments offering ECT and 58% of the hospitals that do not conduct ECT replied to the questionnaire. Forty-three percent of the departments offering ECT indicated less than 10 treatment sessions per month. Forty-three percent of hospitals set a fixed number of treatments per course. Maintenance ECT and ECT on an outpatient basis were rather rare, except for a few departments. The major indication for ECT was depression (88%) rather than schizophrenia (8%), mania (3%), or other psychiatric disorders (1%). Propofol was the anesthetic most commonly used (74%). Seven departments (30%) used a sine wave device. Bilateral electrode placement was the preferred option in 91% of all departments and both fixed high dose and dose titration strategy were used equally (both 47.8%). CONCLUSION: The present findings demonstrate that the practice of ECT in Flanders and the Brussels Capital region in 2003 generally was not performed according to the available guidelines. ECT is underused in Flanders and the Brussels Capital region compared with other countries, although it is available in both specialized psychiatric facilities and in the psychiatric departments of general hospitals. 相似文献
96.
Courtois P Nsimba G Jijakli H Sener A Scott FW Malaisse WJ 《Digestive diseases and sciences》2005,50(2):266-275
This study deals with the enteropathy recently identified in diabetes-prone BB rats (BBdp). Diabetes-resistant BB rats (BBc) and BBdp rats were fed from days 32–39 onward either a protective diabetes-retardant hydrolyzed casein diet (HC) or a plant-based diabetogenic (NTP) diet. The NTP diet decreased body weight and plasma insulin in BBc and BBdp rats. The BBdp rats displayed low intestinal invertase and increased intestinal peroxidase activity. In the BBdp rats fed the HC diet, the mucin content 30–35 cm below the pylorus was higher and the gut permeability lower than in the other three rat groups. There was a significant inverse correlation between gut permeability and the insulinogenic index in the BBdp rats fed the HC or NTP diet. Thus, in BBdp rats, the HC diet somehow prevents the increase in gut permeability and the decrease in the insulinogenic index otherwise found in some of these diabetes-prone animals. 相似文献
97.
Diffusion-weighted MR imaging in monitoring the effect of a vascular targeting agent on rhabdomyosarcoma in rats 总被引:18,自引:0,他引:18
Thoeny HC De Keyzer F Chen F Ni Y Landuyt W Verbeken EK Bosmans H Marchal G Hermans R 《Radiology》2005,234(3):756-764
PURPOSE: To evaluate diffusion-weighted magnetic resonance (MR) imaging for monitoring tumor response in rats after administration of combretastatin A4 phosphate. MATERIALS AND METHODS: Study protocol was approved by local ethical committee for animal care and use. Rhabdomyosarcomas implanted subcutaneously in both flanks of 17 rats were evaluated with 1.5-T MR unit by using four-channel wrist coil. Transverse T2-weighted fast spin-echo sequences, T1-weighted spin-echo sequences before and after gadodiamide administration, and transverse echo-planar diffusion-weighted MR examinations were performed before, 1 and 6 hours, and 2 and 9 days after intraperitoneal injection of vascular targeting agent (combretastatin A4 phosphate, 25 mg/kg). Apparent diffusion coefficient (ADC) was automatically calculated from diffusion-weighted MR imaging findings. These findings were compared with histopathologic results at each time point. For statistical analysis, paired Student t tests with Bonferroni correction for multiple testing were used. RESULTS: T1-weighted images before combretastatin administration showed enhancement of solid tumor tissue but not of central necrosis. At 1 and 6 hours after combretastatin injection, enhancement of solid tissue disappeared almost completely, with exception of small peripheral rim. At 2 and 9 days after combretastatin injection, enhancement progressively reappeared in tumor periphery. ADC, however, showed decrease early after combretastatin injection ([1.26 +/- 0.16]x 10(-3) mm2/sec before, [1.18 +/- 0.17]x 10(-3) mm2/sec 1 hour after [P=.0005] and [1.08 +/- 0.14]x 10(-3) mm(2)/sec 6 hours after [P=.0007] combretastatin A4 phosphate injection), histologically corresponding to vessel congestion and vascular shutdown in periphery but no necrosis. An increase of ADC ([1.79 +/- 0.13]x 10(-3) mm2/sec) (P <.0001) 2 days after combretastatin A4 phosphate injection was paralleled by progressive histologic necrosis. A significant (P <.0001) decrease in ADC 9 days after treatment ([1.41 +/- 0.15]x 10(-3) mm2/sec) corresponded to tumor regrowth. CONCLUSION: In addition to basic relaxation-weighted MR imaging and postgadolinium T1-weighted MR imaging to enable prompt detection of vascular shutdown, diffusion-weighted MR imaging was used to discriminate between nonperfused but viable and necrotic tumor tissues for early monitoring of therapeutic effects of vascular targeting agent. 相似文献
98.
Successful use of biosorb osteofixation devices in 165 cranial and maxillofacial cases: a multicenter report 总被引:3,自引:0,他引:3
Ashammakhi N Renier D Arnaud E Marchac D Ninkovic M Donaway D Jones B Serlo W Laurikainen K Törmälä P Waris T 《The Journal of craniofacial surgery》2004,15(4):692-701; discussion 702
Bioabsorbable osteofixation devices were developed to avoid problems associated with metals. Bioabsorbable devices are mostly made of the polymers polylactide, polyglycolide, and their copolymers [polyglycolide-co-polylactide and P(L/DL)LA]. Using the technique of self-reinforcement of bioabsorbable materials, it is possible to manufacture osteofixation devices with ultra high strength. Self-reinforced polyglycolide-co-polylactide 80/20 was selected to make devices (Biosorb PDX) for this study because of its favorable degradation characteristics. The aim of this study was to evaluate the efficacy of using self-reinforced polyglycolide-co-polylactide 80/20 (Biosorb) plates and screws in the fixation of osteotomies in craniomaxillofacial surgery. In a prospective study, 165 patients (161 children and 4 adults) were operated on in four European Union centers (Paris, Innsbruck, London, and Oulu) from May 1, 1998 to January 31, 2002. Indications included correction of dyssynostotic deformities (n = 159), reconstruction of bone defects after trauma (n = 2), tumor removal (n= 2), and treatment of encephalocele (n = 2). Plates used were 0.8, 1, or 1.2 mm thick, and screws had an outer (thread) diameter of 1.5 or 2 mm and a length of 4, 6, or 8 mm. Tacks had an outer diameter of 1.5 or 2 mm and a length of 4 or 6 mm. During surgery, the devices were easy to handle and apply and provided stable fixation apart from 2 cases. Postoperative complications occurred in 12 cases (7.3%), comprising infection (n = 6), bone resorption (n = 4), diabetes insipidus (n = 1), delayed skin wound healing/skin slough (n = 2), and liquorrhea (n = 1). Accordingly, self-reinforced polyglycolide-co-polylactide 80/20 (Biosorb) plates and screws can be used safely and with a favorable outcome in corrective cranioplasties, especially in infants and young children. 相似文献
99.
Esophageal atresia and other visceral anomalies in a modified Adriamycin rat model and their correlations with amniotic fluid volume variations 总被引:1,自引:1,他引:0
França WM Gonçalves A Moraes SG Pereira LA Sbragia L 《Pediatric surgery international》2004,20(8):602-608
The Adriamycin rat model (ARM) has been used to produce visceral malformations in fetuses to explain the mechanisms of foregut division. The models vary in the dosage of Adriamycin (ADR) and in the number of applications. Our study of a modified ARM using 2.2 mg/kg of ADR for 2 days only, intraperitonealy in pregnant rats, is presented. A total of 81 fetuses were obtained with this model from the ADR group, 74 (91%) alive. Uretero-hydronephrosis (UHN) was observed in 70 fetuses (95%), esophageal atresia (EA) in 68 (92%), duodenal atresia (DA) in 68 (92%), bladder hypoplasia (BH) in 67 (90%), plus other malformations. In evaluating amniotic fluid (AF) volume of the fetuses with EA with tracheo-esophageal fistula (TEF) (group I) and EA without TEF (group II), both associated with bilateral UHN when compared with the control group (group III), groups I and II showed higher AF volume in groups I and II than the control group (group III) did (p=0.0001). In conclusion, ARM was adequate to produce EA and other visceral malformations. The use of ADR in a higher dosage for a shorter period of time produced better results than those presented in previous literature. The increase of AF volume obtained in fetuses presenting EA plus bilateral UHN strongly suggests, despite ureteral dilatation (urinary obstruction), that a malformed communication may exist between the urinary system and the amniotic cavity, permitting the existence of polyhydramnios that is due to digestive obstruction such as EA and DA. 相似文献
100.
Hansen TW 《Pediatrics》2004,113(6):1849-51; author reply 1849-51