Comparison of idiotypes of rabbit antibodies against Salmonella abortusequi and tobacco mosaic virus. Study of cross reactions between antibody idiotypes against these 2 antigenic materials

Idiotypic determinants of anti-tabacco mosaic virus (TMV) antibodies produced by different rabbits can sometimes show a very strong similarity. The frequency of precipitin reactions between sera against anti-TMV idiotypes and anti-TMV sera which are not used for their preparation (heterologous reactions) is about 4 %. We have compared idiotypy of anti-TMV antibodies and idiotypy of anti-Salmonella abortus-equi (Sae) antibodies produced by different rabbits. We have observed precipitin reactions between anti-Sae sera and sera against anti-TMV idiotypes and vice versa. However, anti-Sae antibodies do not combine with TMV and vice versa. Anti-idiotypic sera which precipitate anti-TMV antibodies in the homologous anti-TMV serum can also precipitate anti-Sae antibodies in a heterologous anti-Sae serum. In the same way, anti-idiotypic sera which precipitate anti-Sae antibodies in the homologous serum can also precipitate anti-TMV antibodies in a heterologous anti-TMV serum. We have observed 3 heterologous reactions during the study of 1260 reactions in which anti-TMV sera and sera against anti-Sae idiotypes are involved. We have observed 3 heterologous reactions during the study of 436 reactions in which anti-Sae sera and sera against anti-TMV idiotypes are involved. Previous absorption of anti-idiotypic serum by the homologous serum causes these heterologous reactions to disappear. We have observed, in the case of two of these heterologous reactions, that addition to the anti-idiotypic serum of an excess of the heterologous serum IgG could cause the homologous reaction to disappear. These heterologous reactions between sera against different antigens do not seem to imply the rabbit rheumatoid factor-like substance. These reactions imply idiotypy of anti-Sae antibodies and idiotypy of anti-TMV antibodies.     

Capability of human umbilical cord blood progenitor-derived endothelial cells to form an efficient lining on a polyester vascular graft in vitro

One of the goals of vascular tissue engineering is to create functional conduits for small-diameter bypass grafting. The present biocompatibility study was undertaken to check the ability of cord blood progenitor-derived endothelial cells (PDECs) to take the place of endothelial cells in vascular tissue engineering. After isolation, culture and characterization of endothelial progenitor cells, the following parameters were explored, with a commercial knitted polyester prosthesis (Polymaille C, Laboratoires Pérouse, France) impregnated with collagen: cell adhesion and proliferation, colonization, cell retention on exposure to flow, and the ability of PDECs to be regulated by arterial shear stress via mRNA levels. PDECs were able to adhere to commercial collagen-coated vascular grafts in serum-free conditions, and were maintained but did not proliferate when seeded at 2.0 x 10(5) cm(-2). Cellularized conduits were analyzed by histology and histochemical staining, demonstrating collagen impregnation and the endothelial characteristics of the colonizing cells. Thirty-six hours after cell seeding the grafts were maintained for 6 h of either static conditions (controls) or application of pulsatile laminar shear stress, which restored the integrity of the monolayer. Finally, quantitative real-time RT-PCR analysis performed at 4 and 8 h from cells lining grafts showed that MMP1 mRNA only was increased at 4h whereas vWF, VE-cadherin and KDR were not significantly modified at 4 and 8 h. Our results show that human cord blood PDECs are capable of forming an efficient lining and to withstand shear stress.     

Interferon-alpha 2b modulation of doxorubicin sensitivity in a multidrug resistant cell line.

We evaluated the effect of interferon-alpha2b as a chemosensitiser on HCT-15 cell line in treatment with doxorubicin. Chemosensitivity was determined by [3H]-thymidine incorporation and tetrazolium assays. The levels of expression of P-glycoprotein, Bcl-2 oncoprotein and HLA-ABC complex, and cell cycle/apoptosis analysis were determined by flow cytometry. Dox 50 ng/ml - IFN alpha 2b 500 IU/ml treatment inhibited cell proliferation (47.2 +/- 1.4%, p < 0.0001; MTT assay: 40.6 +/- 1.2%, p < 0.0001) and augmented the expression of P-170, Bcl-2 and HLA-ABC, while it didn't exert apoptosis, producing a slight G2/M arrest. A concentration of IFN-alpha2b, that by itself is not cytotoxic, can potentiate the efficacy of the anticancer drug. This effect is not due to a down-modulation of P-170. The absence of apoptosis and augmented levels of Bcl-2 expression suggests that this could be one of the mechanisms of drug resistance exerted by these cells.     

Changes in type B natriuretic peptide (BNP) concentrations during cardiac valve replacement

Objective: The aim of our study was to investigate the ability of BNP levels to reveal the immediate post-surgery cardiac function improvement. We measured the perioperative variations in BNP concentrations in patients scheduled for cardiac surgery with cardiopulmonary bypass (CPB), chronic mitral regurgitation, valvular aortic stenosis, or myocardial ischaemia. Methods: Three groups were included: patients with coronary artery bypass graft (CABG, group I, n=14), aortic (AVR, group II, n=14) or mitral (MVR, group III, n=7) valve replacement. BNP assay was performed at the induction of anesthesia, immediately after the CPB, at the arrival in the intensive care unit, 4 h, 8 h and 12 h after the arrival in ICU. Results and conclusion: The occurring variation in BNP levels after the operation is an increase whatever the corrective surgery, underlying the relative lack of specificity of BNP with regard to the cardiac pathology. Besides iatrogenic cardioplegia one can supposes that cardiac surgery involves other major stimuli such as anesthesia, sternotomia, hemodynamics, post-operative that could influence in a non specific way BNP levels.     

Effects of acute exercise on insulin sensitivity, glucose effectiveness and disposition index in type 2 diabetic patients

AIM: The aim of this work was to quantify the magnitude of changes in insulin sensitivity (S(I)) and glucose effectiveness (S(G)) in response to acute exercise in type 2 diabetic (T2D) patients, as previously studied in non-diabetic subjects. METHODS: Seven T2D patients and seven non-diabetic controls participated in the study. Two intravenous glucose tolerance tests (0.5 g/kg) with frequent blood sampling over 180 minutes and mathematical modelling were carried out in a randomized fashion, one at rest and the other immediately following 15 minutes of exercise at 50% of the maximum theoretical heart rate (HR(max)) followed by five minutes at 85% of the HR(max). S(I) and S(G) were calculated using Bergman's minimal model. RESULTS: After exercise, S(I) was increased by 773% (from 0.62+/-0.16 to 5.41+/-1.59 min(-1) x 10(-4)/(microU/mL) and even reached the zone of control values at rest (5.52+/-2.28), whereas S(G) remained unchanged. The disposition index acute insulin response (AIR(G)) x S(I) and the product of fasting insulin (I(B)) x S(I) also increased after exercise. CONCLUSION: A single bout of exercise at moderate intensity in type 2 diabetics did not improve S(G), but markedly improved the low S(I) values found in these patients, indicating that the acute effects of exercise on S(I) are quantitatively important in the interpretation of training-related S(I) changes and may even be therapeutically useful on their own. Surrogates such as homoeostasis model assessment (HOMA) and quantitative insulin-sensitivity check index (QUICKI) were not sensitive enough to detect this increase in S(I) and should probably be used with caution in the follow-up of exercise protocols in diabetic patients.     

Cell interactions between human progenitor-derived endothelial cells and human mesenchymal stem cells in a three-dimensional macroporous polysaccharide-based scaffold promote osteogenesis

Several studies have reported the benefits of mesenchymal stem cells (MSCs) for bone tissue engineering. However, vascularization remains one of the main obstacles that must be overcome to reconstruct large bone defects. In vitro prevascularization of the three-dimensional (3-D) constructs using co-cultures of human progenitor-derived endothelial cells (PDECs) with human bone marrow mesenchymal stem cells (HBMSCs) appeared as a potential strategy. However, the crosstalk between the two lineages has been studied in two-dimensional (2-D), but remains unknown in 3-D. The aim of this study is to investigate the cell interactions between PDECs and HBMSCs in a porous matrix composed of polysaccharides. This biodegradable scaffold promotes cell interactions by inducing multicellular aggregates composed of HBMSCs surrounded by PDECs. Cell aggregation contributes to the formation of junctional proteins composed of Connexin43 (Cx43) and VE-cadherin, and an activation of osteoblastic differentiation of HBMSCs stimulated by the presence of PDECs. Inhibition of Cx43 by mimetic peptide 43GAP27 induced a decrease in mRNA levels of Cx43 and all the bone-specific markers. Finally, subcutaneous implantations for 3 and 8 weeks in NOG mice revealed an increase in osteoid formation with the tissue-engineered constructs seeded with HBMSCs/PDECs compared with those loaded with HBMSCs alone. Taking together, these results demonstrate that this 3-D microenvironment favored cell communication, osteogenesis and bone formation.     

The treatment of pain in patients with serious burns

The assessment and treatment of pain in patients with serious burns concerns continuous pain and occasional pain provoked by care procedures.The patient must be included in this therapeutic project.The control of pain is a measure of the quality and effectiveness of the care provided.     

'A phase II study of oral uracil/ftorafur (UFT) plus leucovorin combined with oxaliplatin (TEGAFOX) as first-line treatment in patients with metastatic colorectal cancer'

This phase II trial was performed to evaluate the efficacy and tolerability of a new combination of Uracil/Ftorafur (UFT)/leucovorin (LV) and oxaliplatin in patients (pts) with metastatic colorectal cancer (MCRC) who had not received prior chemotherapy for metastatic disease. Between February 2002 and October 2002, 64 patients received UFT 300 mg m(-2) day(-1) and LV 90 mg day(-1) from day 1 to day 14 combined with oxaliplatin 130 mg m(-2) on day 1, every 3 weeks. All patients were evaluable for safety analysis and 58 of 64 patients were eligible for efficacy. Responses were reviewed by an independent review committee. Of the 58 per-protocol defined assessable patients, 1 complete response and 20 partial responses were observed yielding a response rate of 34% (95% CI: 22-47). The median response duration was 8.74 months (range 1.6-14). The median time to progression and the median survival were 5.88 months (95% CI: 4.34-8.21) and 18.2 months (95% CI: 10-20.7), respectively. Diarrhoea and peripheral neuropathy were the most frequent and predictable toxicities. These events were reversible, noncumulative and manageable. Grade 3 diarrhoea occurred in only 11% of the patients. No grade 4 gastrointestinal toxicity was reported in the study. The incidence of grade 3/4 (National Cancer Institute Common Toxicity Criteria 2: NCI-CTC 2) peripheral neuropathy was 15%. Haematological toxicity was of mild to moderate intensity with 10% of the patients with Grade 3/4 neutropenia without any episode of complication. The TEGAFOX regimen, a new combination using UFT/LV and oxaliplatin every 3 weeks is feasible on an outpatient basis. The combination is safe and active and may offer a promising alternative to the intravenous route. Nevertheless this efficacy results should be confirmed by randomized phase III trials.     

The chronic oral administration of arginine aspartate decreases secretion of IGF-1 and IGFBP-3 in healthy volunteers

To investigate the effect of chronic oral arginine aspartate on the growth hormone (GH), GH-releasing hormone (GHRH), insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) secretions in healthy volunteers. Twenty-three healthy non-athlete volunteer males were administered arginine aspartate (30 g) orally once daily at 21:00 h for 21 consecutive days. Subjects were hospitalized on days 0, 1, 3, 5, 7, 14 and 21 of treatment. At each hospitalization, concentrations of GHRH, GH, IGF-1 and IGFBP-3 were measured over 4 h after arginine aspartate intake. GH, IGF-1 and IGFBP-3 concentrations were also determined over 12 h at days 0, 1 and 21. Compared with day 1, 4 h GH levels dropped at day 5 and subsequently rose to levels not significantly different from initial ones. The latter was substantiated by 12 h GH levels that did not significantly change from days 1 to 21. GHRH levels were not statistically different, although there was a trend in median values that seemed to inversely mirror those of GH. This dynamic over the course of the study for GH and GHRH was accompanied by a general decrease in IGF-1 and IGFBP-3. In healthy volunteers, a chronic oral treatment with 30 g/day arginine aspartate is followed by a decrease in IGF-1 and IGFBP-3 secretions.