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Biomedical subjects

B Fellström

Publications and source records attributed to B Fellström.

At least 55 records · Page 3Linked to original sources
PubMed1996

alpha-Trinositol: a functional (non-receptor) neuropeptide Y antagonist in vasculature.

Neuropeptide Y is a sympathetic co-neurotransmitter released with noradrenaline upon sympathetic nerve stimulation. This study describes the ability of a synthetic inositol phosphate, alpha-trinositol(D-myo-inositol 1,2,6-triphosphate; PP 56) to antagonize vasoconstrictor responses to neuropeptide Y in-vitro as well as in-vivo. In human and guinea-pig isolated arteries alpha-trinositol potently (10 nM to 1 microM extracellular concentration) suppressed the constriction evoked by neuropeptide Y alone, the potentiation by neuropeptide Y of noradrenaline-evoked constriction, and the neuropeptide Y-induced inhibition of relaxation. Moreover, in the pithed (areflexive) rat, a non-adrenergic portion of the pressor response to preganglionic sympathetic nerve stimulation was sensitive to alpha-trinositol. As studied in the recently cloned human (vascular-type) Y1 receptor, the action of alpha-trinositol does not occur through antagonism at the neuropeptide Y recognition site nor does it induce allosteric changes of this receptor. However, we found alpha-trinositol to inhibit the rise in intracellular Ca2+ as well as inositol triphosphate concentrations induced by neuropeptide Y. It is, therefore, proposed that alpha-trinositol represents a non-receptor, but yet selective antagonist of neuropeptide Y in vasculature, opening up the possibility to investigate involvement of neuropeptide Y in sympathetic blood pressure control and in cardiovascular disorders.

Adrenergic alpha-Antagonists↗
PubMed1996

Ischemia-induced transplant arteriosclerosis in the rat. Induction of peptide growth factor expression.

Peptide growth factors have been reported to contribute to the atherogenic process, and they are known to mediate signals for vascular remodeling. Using syngeneic and allogeneic rat aorta transplant models, we analyzed the impact of cold ischemia time up to 24 hours and reperfusion injury on development of transplant arteriosclerosis during the first 2 months after transplantation. The expression of the transforming growth factor-beta (TGF-beta) family as well as the platelet-derived growth factor (PDGF) and its receptors was studied by use of immunohistochemistry, followed by semiquantitative evaluation and multivariate analysis. In the syngeneically transplanted aortas, the expression of TGF-beta 1, PDGF, and the two PDGF receptors in the neointima increased significantly with the extent of cold ischemia time. Furthermore, there was a significant induction of the latent TGF-beta binding protein in the neointima as well as TGF-beta 2 in the media, both correlating with the observation time after transplantation. In the allogeneic grafts, all examined proteins were already induced strongly 2 weeks after transplantation, even at the shortest ischemic period studied (1 hour). However, no positive correlation between growth factor expression and cold ischemia or observation time could be found. Double immunohistochemistry revealed that macrophages express PDGF and its receptors as well as TGF-beta 1. Smooth muscle cells express both types of PDGF receptors, and a few T cells express TGF-beta 1 as well as PDGF receptors. In summary, TGF-beta and PDGF are induced by allogeneic as well as ischemic stimuli in transplanted aortas, suggesting a role in the pathogenesis of transplant arteriosclerosis and representing a potential target for therapeutic intervention.

Animals↗
PubMed1995

Hyperlipidaemia in renal transplantation--risk factor for long-term graft outcome.

The role of hyperlipidaemia for the outcome of renal transplantation was evaluated in a prospective study involving 151 patients. Graft losses were associated with more pronounced pre-transplant lipid abnormalities. An increased risk of graft loss during the first two post-transplant years was found in patients with marked pre-transplant hypercholesterolaemia (> or = 6.9 mmol L-1, P = 0.014; relative risk 2.2). Hypercholesterolaemia > or = 6.9 mmol L-1 at 6 months after transplantation, present in 41/115 patients, was associated with a lower GFR (P = 0.007) and more pronounced albuminuria (P = 0.009) at 2 years. In patients with graft dysfunction (serum creatinine > 160 mumol L-1) at 2 years, more pronounced lipid abnormalities before and at 6 months after transplantation were found. Between 6 months and 2 years, total and LDL cholesterol did not change significantly, but HDL cholesterol decreased (P = 0.03). In conclusion, hyperlipidaemia is also a risk factor for the long-term outcome in renal transplantation. Further investigations are needed to determine whether graft losses and late graft failure can be prevented or ameliorated by treating hyperlipidaemia in renal transplantation.

Adolescent↗
PubMed1995

Can histopathological findings in early renal allograft biopsies identify patients at risk for chronic vascular rejection?

In order to assess the prognostic value of renal transplant biopsies for identifying patients at risk for chronic vascular rejection (CVR), 99 biopsies performed at 6 months after renal transplantation were evaluated as part of a prospective study. A chronic graft damage (CGD) score was calculated from the scores of vascular intimal hyperplasia, glomerular mesangial changes, focal lymphocytic infiltration, focal and diffuse interstitial fibrosis, and tubular atrophy, features compatible with CVR. The mean score for the whole patient population was 4.7 +/- 2.9 (range 0-11). There was a strong association between the CGD score at 6 months and the risk of graft loss up to 2 and 3 years following transplantation. Patients with a CGD-score of > or = 6 had a higher graft loss rate at 2 years than those with a score of < 6 (6/35 vs 2/54; p = 0.037). In patients with a functioning graft at 2 years, the CGD-score at 6 months correlated with graft function at 2 years. In addition to higher serum creatinine (p = 0.003) and lower GFR (p = 0.01), patients with a CGD-score of > or = 6 at 6 months also had a higher degree of albuminuria (p = 0.008) at 2 years as compared with patients with a CGD-score of < 6. At 3 years 10/35 patients with a CGD score of > or = 6 and 2/54 patients with a CGD-score of < 6 had lost their grafts (p = 0.002). The relative risk for graft loss associated with a CGD-score of > or = 6 was 7.65.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Ischemia-induced transplant arteriosclerosis in the rat.

The effect of cold graft ischemia time on the development of transplant arteriosclerosis was investigated. Aorta grafts from DA or PVG rats were stored in a cold perfusion solution for 1, 4, or 24 hours before being orthotopically transplanted to PVG recipients. After observation times ranging from 2 to 8 weeks, the grafts were examined for various cell populations. Regional changes in the intima and media layers were measured by using an image analysis system. The arteriosclerosis-like changes seen in syngeneic grafts with the longest ischemia time could be almost as prominent as those seen in the allogeneic transplants. The magnitude of the regional intima changes in the syngeneic group correlated well with the ischemia time and in the allogeneic group with the observation time. The cell composition found in the intima and media of the allogeneic vessels consisted of macrophages, T-lymphocytes, MHC class II-expressing cells, and smooth muscle cells, whereas the syngeneic grafts contained almost exclusively smooth muscle cells and macrophages. We therefore conclude that the damage due to prolonged cold ischemia time is sufficient to cause pronounced graft arteriosclerosis. The pathophysiological mechanism leading to ischemia-induced arteriosclerosis is different from the one seen in the allogeneic situation.

Animals↗
PubMed1994

Treatment of renal calcium stone disease with the synthetic glycosaminoglycan pentosan polysulphate.

Glycosaminoglycans (GAGs) are potent inhibitors of calcium oxalate growth and aggregation. The synthetic GAG pentosan polysulphate (PPS) was used in the treatment of patients with renal calcium stone disease. Altogether, 121 patients were included in an open trial over a 3-year-period. The average stone episode rate and the stone operation rate were no different during treatment and in the pretreatment period. Altogether 48% of the patients were entirely stone-free during follow-up, whereas 29/56 patients who continued to form stones reported smaller stones that were more easily passed. It is concluded that there may be a role for PPS in the treatment of recurrent renal calcium stone disease, but a controlled study may be needed.

Calcium↗
PubMed1993

Induction of transforming growth factor-beta during cardiac allograft rejection.

The polypeptides of the transforming growth factor-beta (TGF-beta) family are potent endogenous immuno-regulators. Using a rat cardiac allograft transplant model, we investigated the expression of the precursor forms of TGF-beta 1, TGF-beta 2, and TGF-beta 3 and the latent TGF-beta binding protein (LTBP) by immunohistochemistry. The activity of TGF-beta in the extracts from transplanted as well as normal hearts was measured using a bioassay, and Northern blot analysis was performed on RNA extracts. The transplanted hearts were analyzed both during acute rejection up to 6 days and during chronic rejection up to 6 mo after transplantation and compared with normal controls. The animals of the chronic rejection group received cyclosporin A for immunosuppression. The TGF-beta bioactivity dramatically increased in the transplanted allografts during the chronic rejection process compared to the normal hearts, and so did the immunostaining as well as the mRNA levels for TGF-beta 1 and, to a lesser extent, the immunostaining for TGF-beta 2. TGF-beta 3 expression remained unchanged and was only found in the myocardium in trace amounts. During the acute rejection process up to 6 days after transplantation, TGF-beta immunoreactivity increased only slightly, whereas the TGF-beta mRNA was severalfold increased. Control animals treated with cyclosporin A showed a similar pattern at day 6 with regard to TGF-beta expression. LTBP was induced simultaneously with TGF-beta 1 and occurred within interstitial spaces of the myocardium. The TGF-beta was produced by macrophage-like infiltrating lymphocytes. In conclusion, highly elevated levels of TGF-beta and LTBP were found during chronic rejection of cardiac allografts in rats. The induction of TGF-beta may counteract the rejection process and could be useful for new therapeutic approaches in the prevention of allograft rejection.

Animals↗
PubMed1993

The influence of pretransplant lipoprotein abnormalities on the early results of renal transplantation.

Lipoprotein patterns were investigated before and after renal transplantation in a prospective study including 151 patients. Kidney graft losses during the first 6 months were associated with higher total cholesterol (P = 0.03), LDL cholesterol (P = 0.003) and LDL triglyceride levels (P = 0.01) before transplantation. Patients with serum cholesterol > or = 6.9 mmol l-1 before transplantation had more acute rejections (1.7 vs. 0.9), a worse graft function and more vascular intimal hyperplasia and glomerular mesangial changes in transplant biopsies at 6 months. Patients with serum creatinine levels exceeding 160 mumol l-1 at 6 months had more severe lipid disorders already before transplantation. Serum creatinine at 6 months was influenced by the number of acute rejection episodes (P = 0.0001) and the age of the donor (P = 0.009) while the number of acute rejections was found to be related to pretransplant total cholesterol levels (P = 0.0086) and the age of the recipient (P = 0.025). In conclusion, pretransplant lipoprotein disturbances have an impact on the early outcome of renal transplantation. Since there is a progression of hyperlipidaemia following transplantation, this may have an influence also on the cardiovascular morbidity and late graft dysfunction.

Adolescent↗