Molecular Targeting with Recombinant Cytotoxins of Interleukin-13 Receptor α 2-expressing Glioma

A restricted receptor for interleukin 13 (IL-13R2) is over-expressed in high-grade astrocytoma (HGA), but not in normal organs. In order to design and examine new anti-HGA therapies, which are molecularly directed against IL-13R2, we established an IL-13R2-expressing syngeneic immunocompetent murine model of HGA. The model was obtained by transfecting G-26 murine glioma cells with IL-13R2. G-26-IL-13R2(+) cells, but not mock-transfected cells, became susceptible to IL-13 mutant-based cytotoxic proteins that kill human HGA cells. G-26-IL-13R2(+) cells maintained their tumorigenicity in immunocompetent C57BL/J6 mice and preserved their expression of IL-13R2 in vivo. These characteristics of the G-26-IL-13R2(+) tumors allowed us to test molecularly defined anti-glioma passive immunotherapy. A targeted recombinant chimera cytotoxin composed of multiply mutated IL-13 (IL-13.E13Y/R66D/S69D) and a derivative of Pseudomonas exotoxin (PE), PE1E, IL-13.E13Y/R66D/S69D-PE1E, was used in anti-tumor experiments. G-26-IL-13R2(+) cells were killed by IL-13.E13Y/R66D/S69D-PE1E in an IL-4-independent fashion. To test the cytotoxin in vivo, G-26-IL-13R2(+) tumors were established in C57BL/J6 mice and when the tumors reached a size of at least 50mm³, the mice were treated with IL-13.E13Y/R66D/S69D-PE1E. In the mice treated with the targeted fusion cytotoxin, the tumors regressed and 80% of the animals were cured. This study documents the establishment of an IL-13R2-positive model of HGA in immunocompetent rodents. Furthermore, the effectiveness and safety of the targeted IL-13-based cytotoxin against IL-13R2-expressing tumors in a more clinically relevant in vivo HGA model is promising with regard to the future clinical utility of the cytotoxin.     

Chronomics: circadian and circaseptan timing of radiotherapy, drugs, calories, perhaps nutriceuticals and beyond

We suggest a putative benefit from timing nutriceuticals (substances that are both nutrients and pharmaceuticals) such as antioxidants for preventive or curative health care, based on the proven merits of timing nutrients, drugs, and other treatments, as documented, i.a., in India. The necessity of timing melatonin, a major antioxidant, is noted. A protocol to extend the scope of chronoradiotherapy awaits testing. Imaging in time by mapping rhythms and broader time structures, chronomes, for earliest diagnoses, for example detection of vascular disease risk, is recommended. The study of rhythms and broader chronomes leads to a dynamic functional genomics, guided by imaging in time of free radicals and antioxidants, amongst many other variables.     

Effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants

BACKGROUND: Glutamine is one of the most abundant amino acids in both plasma and human milk and may be conditionally essential in premature infants. However, glutamine is not provided by standard intravenous amino acid solutions. OBJECTIVE: We assessed the effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants receiving parenteral nutrition (PN). DESIGN: A total of 141 infants with birth weights of 401-1000 g were randomly assigned to receive a standard intravenous amino acid solution that did not contain glutamine or an isonitrogenous amino acid solution with 20% of the total amino acids as glutamine. Blood samples were obtained just before initiation of study PN and again after the infants had received study PN (mean intake: 2.3 +/- 1.0 g amino acids x kg(-1) x d(-1)) for approximately 10 d. RESULTS: Infants randomly assigned to receive glutamine had mean plasma glutamine concentrations that increased significantly and were approximately 30% higher than those in the control group in response to PN (425 +/- 182 and 332 +/- 148 micromol/L for the glutamine and control groups, respectively). There was no significant difference between the 2 groups in the relative change in plasma glutamate concentration between the baseline and PN samples. In both groups, there were significant decreases in plasma phenylalanine and tyrosine between the baseline and PN samples; the decrease in tyrosine was greater in the group that received glutamine. CONCLUSIONS: In extremely low-birth-weight infants, parenteral glutamine supplementation can increase plasma glutamine concentrations without apparent biochemical risk. Currently available amino acid solutions are likely to be suboptimal in their supply of phenylalanine, tyrosine, or both for these infants.     

Management of dementia in primary health care: the experiences of collaboration between the GP and the district nurse

OBJECTIVE: The objective of this study was to explore the context and experiences of collaboration between the GP and the district nurse (DN) in diagnosing dementia, in order to identify possible procedures to improve care. METHODS: Two group interviews were conducted with four DNs and five GPs, respectively, working in the municipality of Copenhagen. RESULTS: The group interviews revealed that the suboptimized collaboration could be due to different inter-professional diagnostic strategies and a lack of understanding of the importance of early, shared, decision making. This could create conflicts between the groups. CONCLUSIONS: This study indicates a possibility for improved collaboration between the two professional groups in diagnosing dementia. Possible approaches for improved care should focus on an inter-professional understanding of the importance of early, shared, decision making, emphasizing early identification and care of diagnosed demented patients. Establishing a shared collaboration model including out-patient memory clinics, GPs and DNs could be a first step. This model should also take into account an evaluation of possible consequences for the diagnosed demented patients in terms of treatment and care and consider the indication for referrals to a comprehensive diagnostic evaluation. We are at present planning a study to address these aspects.     

Über Stichverletzungen des Kopfes. (Ein Schädel mit über 30 Stichen)

Ohne Zusammenfassung Mit 5 Textabbildungen.     

Removal of broken interlocking nails and reosteosynthesis--related clinical problems]

Nine patients with six fractures of the intramedullary cannulated nails and four Gamma nails are presented. In five patients broken implants had been removed by simple and safe method by use of tape extractor and than four patients has had intramedullary reosteosynthesis by closed method. The main causes in most cases were technical errors and early full weighbearing.     

Anatomopathological study in BALB/c mice brains experimentally infected with Toxoplasma gondii.

Toxoplasmosis is one of the most important diseases of the nervous central system, leading to severe symptoms and, many times, irreversible sequelae. This work demonstrated the main anatomopathological lesions caused by Toxoplasma gondii in brains from experimentally infected BALB/c mice. We analyzed 51 cases of mice that developed toxoplasmosis after experimental infection by intraperitoneal inoculation of blood, amniotic liquid and cerebrospinal fluid from fetuses, newly born children and pregnant women with clinical and laboratory signals of toxoplasmosis. In all experiments where we detected the parasite in mice we also detected pathological lesions in the animal brains with great polymorphism between experiments. Edema was the most found lesion in all cases. Besides, it was possible to demonstrate the inflammatory process in 82.4% of cases and necrosis in 64.7% of cases, in agreement with the literature that describes severe neurological damage in its hosts.