Biomedical subjects

C Booy

Publications and source records attributed to C Booy.

17 recordsLinked to original sources

PubMed2005

Hypoxia aggravates lipopolysaccharide-induced lung injury.

The animal model of inflammatory response induced by intratracheal application of lipopolysaccharide includes many typical features of acute lung injury or the acute respiratory distress syndrome. A number of experimental investigations have been performed to characterize the nature of this injury more effectively. In inflammatory conditions, hypoxia occurs frequently before and in parallel with pulmonary and non-pulmonary pathological events. This current study was designed to examine the in vivo effect of hypoxia as a potentially aggravating condition in endotoxin-induced lung injury. Lipopolysaccharide, 150 microg, was instilled intratracheally into rat lungs, and thereafter animals were exposed to either normoxia or hypoxia (10% oxygen). Lungs were collected 2, 4, 6 and 8 h later. Inflammatory response and tissue damage were evaluated by quantitative analysis of inflammatory cells and mediators, surfactant protein and vascular permeability. A significantly enhanced neutrophil recruitment was seen in lipopolysaccharide-animals exposed to hypoxia compared to lipopolysaccharide-animals under normoxia. This increased neutrophil accumulation was triggered by inflammatory mediators such as tumour necrosis factor-alpha and macrophage inflammatory protein-1beta, secreted by alveolar macrophages. Determination of vascular permeability and surfactant protein-B showed enhanced concentrations in lipopolysaccharide-lungs exposed to hypoxia, which was absent in animals previously alveolar macrophage-depleted. This study demonstrates that hypoxia aggravates lipopolysaccharide injury and therefore represents a second hit injury. The additional hypoxia-induced inflammatory reaction seems to be predominantly localized in the respiratory compartment, underlining the compartmentalized nature of the inflammatory response.

Animals↗

PubMed2004

Release of inflammatory mediators in irradiated cell salvage blood and their biological consequences in human beings following transfusion.

BACKGROUND AND OBJECTIVE: Irradiation of intraoperative cell salvage blood has recently been used to inactivate tumour cells before retransfusion, during cancer surgery. No information is available about a potential inflammatory response of the recipient to the retransfusion of irradiated intraoperative cell salvage blood. This pilot study was conducted to investigate the possible release of the pro-inflammatory mediators, tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), eotaxin and monocyte chemo-attractant protein-1 (MCP-1), in the serum of recipients by intraoperative retransfusion of irradiated intraoperative cell salvage blood. METHODS: Nine patients undergoing gynaecological cancer surgery were included in this study. Intraoperative cell salvage blood was irradiated with 50 Gy and retransfused to the patient. Serum and intraoperative cell salvage blood concentrations of TNF-alpha, IL-1beta, eotaxin and MCP-1 were repeatedly analysed before and after retransfusion, respectively before and after irradiation. RESULTS: Traces of mediators were detected in intraoperative cell salvage blood but no increase due to irradiation was observed. Following transfusion of intraoperative cell salvage blood, minute quantities (all < 30 pg mL(-1) of mediators were detected in the serum of patients. However, there was no significant upregulation compared to serum values before retransfusion. CONCLUSIONS: These results provide evidence that retransfusion of irradiated intraoperative cell salvage blood might represent a blood-saving strategy in cancer surgery without an immunological inflammatory response as shown by a lack of upregulation of inflammatory mediators.

Aged↗

PubMed2002

Decreased alveolar oxygen induces lung inflammation.

Molecular mechanisms of the inflammatory reaction in hypoxia-induced lung injury are not well defined. Therefore, effects of alveolar hypoxia were studied in rat lungs, exposing rats to 10% oxygen over periods of 1, 2, 4, 6, and 8 h. An increase in the number of macrophages in bronchoalveolar lavage fluid of hypoxic animals was shown between 1 and 8 h. Extravasation of albumin was enhanced after 1 h and remained increased throughout the study period. NF-kappaB-binding activity as well as mRNA for TNF-alpha, macrophage inflammatory protein (MIP)-1beta, and monocyte chemoattractant protein (MCP)-1 were increased within the first 2 h of exposure to hypoxia. Hypoxia-inducible factor (HIF)-1alpha and intercellular adhesion molecule (ICAM)-1 mRNA were upregulated between 1 and 6 h. Elimination of alveolar macrophages by intratracheal application of liposome-encapsulated clodronate led to a decreased expression of NF-kappaB binding activity, HIF-1alpha, TNF-alpha, ICAM-1, and MIP-1beta. In summary, alveolar hypoxia induced macrophage recruitment, an increase in albumin leakage, and enhanced expression of inflammatory mediators, which were mainly macrophage dependent. Alveolar macrophages appear to have a prominent role in the inflammatory response in hypoxia-induced lung injury and the related upregulation of inflammatory mediators.

Animals↗

PubMed2001

Heterozygosity for the factor V Leiden (G1691A) mutation predisposes renal transplant recipients to thrombotic complications and graft loss.

BACKGROUND: Heterozygosity for a mutation in the coagulation factor V gene (factor V Leiden; FVL) leads to resistance to activated protein C and represents the most common cause of inherited thrombophilia. FVL is associated with a high risk for thromboembolic events and might be a risk factor for venous thrombosis and early graft loss in renal transplant recipients. METHODS: We studied a cohort of 202 renal allograft recipients to assess the impact of the FVL mutation on thrombotic events and graft loss within 1 year after transplantation. We recorded the occurrence of deep venous thrombosis, pulmonary embolism, early graft perfusion defect, and graft loss. The occurrence of these events was then correlated with the presence or absence of heterozygosity for the FVL mutation. RESULTS: Heterozygosity for FVL was detected in 8 (4%) of 202 patients. The incidence of deep venous thrombosis or pulmonary embolism was higher in heterozygous compared with wild-type patients (25% vs. 5.7%, P=0.09). Furthermore, early graft perfusion defect (25% vs. 2.6%; P=0.03) and graft loss within 7 days after transplantation (2/8 vs. 1/194; P=0.004) were significantly more frequent among heterozygous carriers of FVL. All eight FVL carriers were negative for protein C or S deficiency and antiphospholipid and anticardiolipin antibodies, and were not carriers of the G20210A prothrombin mutation. CONCLUSIONS: Heterozygosity for the FVL mutation predisposes renal allograft recipients to venous thromboembolic complications, graft perfusion defects, and early transplant loss. Screening for the FVL mutation and appropriate peri- and postoperative anticoagulation after renal transplantation might prevent these thromboembolic complications.

Cohort Studies↗

PubMed2001

Suppression of ICAM-1 expression in renal proximal tubular cells by 1,25-dihydroxyvitamin D3.

BACKGROUND: 1,25-Dihydroxyvitamin D(3) is mainly synthesized by renal proximal tubular cells. More recently, it has been shown to affect cell growth and TGF-beta(1) synthesis in glomerular and tubular renal cells in vitro, and to prevent glomerulosclerosis in vivo in subtotally nephrectomized rats. The mechanisms involved have not been fully identified. We asked whether 1,25-vitamin D(3) might interact with additional immunoregulatory functions of renal cells by studying its effects on the expression of the cellular adhesion molecules ICAM-1 (CD54) and VCAM-1 (CD106) in human proximal tubular cells in vitro (HK-2 cells). METHODS: Expression of adhesion molecules was assessed in HK-2 cells cultured under basal conditions and after stimulation with TNF-alpha plus IFN-gamma, by flow cytometry, gene transcription (RT-PCR) and measurement of soluble ICAM-1 in culture supernatant by ELISA. RESULTS: Unstimulated HK-2 cells did not express VCAM-1 and only little ICAM-1. 1,25-Vitamin D(3) had no effect on the expression of adhesion molecules in unstimulated cells. TNF/IFN stimulation resulted in a 4-fold increase in ICAM-1 and VCAM-1 expression. The TNF/IFN-induced increase in ICAM-1 expression was reduced by 1,25-vitamin D(3) dose dependently (10(-7) M vs. solvent: -30%; 10(-9) M: -18%; 10(-11) M: -17%). 25(OH)-vitamin D(3) had no effect. ICAM-1 mRNA concentration was increased in TNF/IFN-stimulated cells. 1,25-Vitamin D(3) treatment prevented the increase of ICAM-1 mRNA by 27% after 24-72 h incubation (p = 0.03). The TNF/IFN-induced increase in soluble ICAM in culture supernatants was unchanged by 1,25-vitamin D(3). VCAM-1 expression was unchanged by incubation with 1,25-vitamin D(3) under basal conditions and after TNF/IFN stimulation. CONCLUSION: 1,25-Vitamin D(3) inhibits cytokine-induced ICAM-1 but not VCAM-1 expression in renal proximal tubular cells in vitro. The present data support the hypothesis that 1,25-vitamin D(3) is not only synthesized by renal tubular cells, but may also affect immunoregulatory functions in these cells.

Calcifediol↗

PubMed2000

The 825C/T polymorphism of the G-protein subunit beta3 does not influence blood pressure and renal function in kidney transplant recipients.

BACKGROUND: Recently, a polymorphism at position 825 (C-->T) of the cDNA that encodes the beta3 subunit of heterotrimeric G proteins (Gbeta3) was found to be associated with essential hypertension. The T allele leads to the formation of a truncated splice variant (Gbeta3-s) with enhanced activity, promoting hypertension. We examined whether the T allele had an influence on blood pressure (BP) and early renal function after renal transplantation. METHODS: We determined the Gbeta3 genotype and T allele frequencies in renal transplant patients and examined associations with BP, BP medications, and renal function in the first year after transplantation. RESULTS: In renal transplant recipients (n=216) the frequency of the T allele was marginally increased (0.34 vs 0.29) compared with normal healthy blood donors (n=163). Age, sex and body mass index were similar in patients with the CC, CT and TT genotype. BP, number of BP medications, and serum creatinine levels were also similar for the three genotypes within the first year after transplantation. Significantly more patients with the TT genotype (48%) had glomerulonephritis as the underlying renal disease, compared with the CT (29%) and CC (27%) genotypes. CONCLUSIONS: The T allele of Gbeta3 does not have a negative impact on BP and early renal function in recipients of a renal allograft. The T allele might play a role in the pathogenesis of chronic glomerulonephritides.

Adult↗

PubMed1999

1,25-dihydroxyvitamin D3 stimulates transforming growth factor-beta1 synthesis by mouse renal proximal tubular cells.

1,25-dihydroxyvitamin D3 [1,25-(OH)2 D3] is a secosteroid hormone with effects on cell growth, differentiation and immunoregulatory functions in a number of tissues not primarily involved in mineral metabolism. We recently demonstrated growth-regulating effects of 1, 25-(OH)2 D3 on human mesangial cells and proximal tubular cells. To investigate whether 1,25-(OH)2 D3 might also affect the synthesis of cytokines and growth factors in proximal tubular cells, we assessed in the present study the expression and secretion of transforming growth factor-beta1 (TGF-beta1) in a mouse proximal tubular cell line (MCT) in vitro. TGF-beta1 synthesis was measured by a monospecific ELISA in culture supernatant. The secreted TGF-beta1 was proven to be biologically active by means of a bioassay system (CCL-64 mink lung epithelial cell proliferation assay). TGF-beta1 gene expression was assessed by RT-PCR. To analyze whether TGF-beta1 expression mediates the 1,25-(OH)2 D3-induced antiproliferative actions in MCT, proliferation studies in the absence or presence of a blocking monoclonal anti TGF-beta1-3 antibody were performed. 1, 25-(OH)2 D3 (10(-11) to 10(-7) M) specifically increased the TGF-beta1 protein secretion in MCT with a maximum at 10(-8) M. No detectable effect was found with 25 D3 at 10 times higher concentrations. A synthetic 20-epi analogue, MC 1288, increased TGF-beta1 secretion up to similar amounts at equimolar concentrations as the natural hormone 1,25-(OH)2 D3. Steady-state TGF-beta1 mRNA concentration in MCT was transiently increased by 1, 25-(OH)2 D3 between 12 and 24 h, returning to control values at 48 h. Blocking TGF-beta1 did not reduce or abrogate the antiproliferative effect of 1,25-(OH)2 D3. In conclusion, 1,25-(OH)2 D3 stimulates TGF-beta1 expression in renal proximal tubular cells, a growth factor with anti-inflammatory and profibrotic actions which plays an important role in the development and progression of nephrosclerosis.

Animals↗

PubMed1996

1,25-dihydroxyvitamin D3 and the synthetic vitamin D analogue, KH 1060, modulate the growth of mouse proximal tubular cells.

Apart from its classical role in bone and mineral metabolism, 1,25-dihydroxyvitamin D3 (1,25-vitamin D3) has recently been shown to affect cell growth and differentiation from a variety of tissues primarily not involved in mineral metabolism and to provide immunomodulatory functions. Findings in human mesangial cells in vitro as well as in rat model of compensatory renal growth in vivo suggest that renal cells are a target for 1,25-vitamin D3. In the present study the effects of 1,25-vitamin D3 and a synthetic vitamin D analogue, KH 1060, on proliferation and protein synthesis were investigated in a mouse proximal tubular cell line (MCT). 1,25-vitamin D3 and KH 1060 inhibited cell proliferation dose dependently (10(-7) to 10(-12) M) and specifically as assessed by 3H-thymidine incorporation (DNA synthesis) and cell counting. The cellular protein concentration, protein synthesis (3H-methionine incorporation) and protein/DNA ratio were not influenced by 1,25-vitamin D3 and KH 1060. By analyzing c-fos and c-myc expression using semiquantitative RT-PCR, a constant basal expression of both protooncogenes, even under serum-free conditions, was found in MCT cells. Phorbol 12-myristate 13-acetate (TPA) further stimulated c-fos and c-myc expression, whereas treatment with 1,25-vitamin D3 (10(-7) M) it had no effect either in unstimulated or in TPA-stimulated cells. In conclusion, 1,25-vitamin D3 and a synthetic vitamin D analogue, KH 1060, provide growth-regulating effects on renal proximal tubular cells in vitro. These effects are not mediated by regulation of c-fos and c-myc. Further studies will have to clarify whether 1,25-vitamin D3 plays a physiologic role in renal development and growth in vivo.

Animals↗

PubMed1991

[Space closure after anterior tooth loss due to trauma].

The orthodontic treatment of space closure after loss of anterior teeth due to trauma asks not only for a dental movement but for careful consideration. These depend on various factors such as age, tooth shape, tooth size, extent of the traumatic damage and the present malocclusion. The possibilities and limits of an orthodontic treatment have to be estimated to allow a correct decision for each patient, whereby some compromise has to be accepted. This is demonstrated with two examples.

Adult↗

PubMed1986