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E Pettersson

Publications and source records attributed to E Pettersson.

At least 37 records · Page 2Linked to original sources
PubMed1997

On the release of glutamate and aspartate in the basal ganglia of the rat: interactions with monoamines and neuropeptides.

Using highly sensitive analytical procedures, glutamate (Glu), aspartate (Asp) and several putative neurotransmitters and metabolites can be monitored simultaneously in the extracellular space of neostriatum, substantia nigra and cerebral cortex of the rat by in vivo microdialysis. Glu and Asp are found at sub-micromolar concentrations in all investigated brain regions. In order to ascertain their neuronal origin, we have extensively studied the sensitivity of extracellular Glu and Asp levels to: (i) K(+)-depolarization, (ii) Na(+)-channel blockade, (iii) removal of extracellular Ca2+, (iv) depletion of presynaptic vesicles, and (v) integrity of neuronal pathways. The relevance of these criteria for several neurotransmitters monitored simultaneously or in parallel experiments has also been examined. The functional interactions among different neuronal pathways in the basal ganglia are studied by using selective pharmacological treatments, administered systemically, or locally via intracerebral injections or the microdialysis perfusion medium. Immunohistochemical evidence for the existence of Glu and/or Asp neuronal pathways in the basal ganglia of the rat is presented, discussing especially new findings indicating the existence of a Glu-independent Asp system, intrinsic to the neostriatum of the rat. The clinical relevance of these interactions is discussed, focusing on the implications for the treatment of neurodegenerative disorders affecting the basal ganglia.

Animals↗
PubMed1997

IgA nephropathy: 30 years on.

Thirty years since its discovery, IgA nephropathy (IgAN) has turned out to be the commonest primary glomerulonephritis around the world. The major presenting symptom is haematuria, with or without proteinuria. IgAN was initially considered a benign disease, but long-term follow-up studies have shown the course to be slowly progressive with up to 50% of the patients developing terminal renal failure after several decades. The aetiology and pathogenesis are still unclear, but IgAN seems to be associated with a dysregulation of the immune response which is not very well understood. There is today no specific treatment. Effective blood pressure control is the cornerstone of therapy.

Glomerulonephritis, IGA↗
PubMed1997

Predisposing factors in sulphasalazine-induced systemic lupus erythematosus.

The aim of this study was to define predisposing factors in patients with sulphasalazine-induced systemic lupus erythematosus (SLE). Eleven patients with onset of SLE or SLE-like syndromes during sulphasalazine treatment are reported. Before the onset of SLE, five of the patients suffered from rheumatoid arthritis (RA), one from psoriatic arthropathy (PsoA), two from juvenile chronic arthritis (JCA) and three from ulcerative colitis (UC). At the time of diagnosis of drug-induced SLE, analysis of antinuclear antibodies (ANA), anti-double-stranded DNA antibodies (anti-dsDNA), anti-histone antibodies (anti-histones), acetylator status of the enzyme N-acetyltransferase 2 (NAT2) and HLA classification were performed. All patients were anti-DNA positive at disease onset and were determined to be slow acetylators. HLA A1 occurred in 4/10 patients, B8 in 5/10. HLA DR 3 was represented in one patient and DR 3(17) in five patients. The DQA1* 0501 allele was observed in 7/10 patients and DQB1 0201* in 6/10. Persistent SLE and development of nephritis were noted in patients with long duration of treatment and high cumulative dose of sulphasalazine (> 1000 g). In sulphasalazine-induced SLE, slow acetylator genotype and HLA haplotypes associated with idiopathic SLE seem to predict disease induction. Further, as the risk of developing persistent SLE and nephritis increases with long-standing sulphasalazine medication, it is of importance to monitor the patients with regard to signs of SLE during the entire treatment period.

Adolescent↗
PubMed1997

Olsalazine-induced lupus syndrome.

A 73 year-old woman with ulcerative colitis developed skin rashes after long-standing sulphasalazine treatment. After a switch to olsalazine, she developed a severe SLE with multiorgan involvement. When the treatment was terminated, the disease manifestations and serological findings resolved.

Aged↗
PubMed1997

Serum ferritin and tissue iron in anemic dialysis patients.

The relationship between serum ferritin and tissue iron was investigated in 26 dialysis patients (17 hemodialysis patients. 9 chronic peritoneal dialysis patients) with anemia (median hemoglobin 74 g/l, range 56-92 g/l). Serum ferritin ranged from 18 to 9,435 micrograms/l (median 450 micrograms/l). Tissue iron was assessed in the liver biopsies of 4 hemodialysis patients with iron overload (serum ferritin 1,150-9,435 micrograms/l), in the muscle biopsies of 5 patients with serum ferritin 170-9,435 micrograms/l, and in bone marrow aspirations (semiquantitative assessment). The mean liver iron concentration was 15.4 +/- 8.0 micrograms Fe/mg protein (mean +/- SD), which is similar to that previously found in patients with untreated idiopathic hemochromatosis. Four patients with serum ferritin 170-620 micrograms/l had muscle iron concentrations (0.33 +/- 0.10 microgram Fe/mg protein) similar to those found in controls (0.23 +/- 0.10, means +/- SD). One patient with serum ferritin 9,435 micrograms/l had a markedly increased muscle iron concentration (1.3 micrograms Fe/mg protein). The bone marrow iron was assessed as negative in 3 patients (serum ferritin 44-85 micrograms/l), positive in 8 (serum ferritin 18-379 micrograms/l), increased in 11 patients (serum ferritin 222-4,210 micrograms/l), and was markedly increased in 2 patients (serum ferritin 4,550 and 9,435 micrograms/l). Bone marrow iron correlated significantly with serum ferritin concentrations (spearman rank correlation coefficient rho = 0.89, p < 0.001). These results show that in dialysis patients with a stable iron balance and unstimulated erythropoiesis, i.e., patients without erythropoietin treatment and parenteral iron, serum ferritin is a useful indicator of iron stores. Our findings also suggest that the relationship between tissue iron and serum ferritin levels in end-stage renal disease is altered, i.e. a relative increase in serum ferritin levels unrelated to iron stores is observed in dialysis patients.

Adult↗
PubMed1996

Evidence for aspartate-immunoreactive neurons in the neostriatum of the rat: modulation by the mesencephalic dopamine pathway via D1-subtype of receptor.

Aspartate-like immunoreactivity was visualized in the neostriatum of rats using indirect immunofluorescence techniques and antibodies raised against aspartate conjugated to keyhole limpet hemocyanine. In normal rats only a few aspartate-positive cell bodies with limited processes were observed. A moderate increase was seen after treatment with (+)methamphetamine and haloperidol. A dramatic increase in the number and fluorescence intensity was observed in the unilaterally 6-hydroxy-dopamine lesioned rats after multiple injections of the D1-dopamine receptor agonist SKF 38393. In these rats strongly fluorescent processes as well as extensive terminal varicose fibre networks were observed. This increase could partly be blocked by the D1-dopamine receptor antagonist SCH 23390. Using a modified technique the aspartate-positive cell bodies and processes were observed even when the antiserum was diluted 1:80,000. Positive cell bodies and fibres were also seen on the ipsilateral side outside the neostriatum, for example in the islet of Calleja and in the piriform cortex. The aspartate-positive cells were negative for dopamine- and cyclic AMP-regulated phosphoprotein-32, a marker for neurons bearing dopamine D1-receptor subtype. A proportion of the aspartate-positive neurons (20%) contained neuropeptide tyrosine-like immunoreactivity. On adjacent sections there was a marked up-regulation of preprodynorphin-like immunoreactivity. The up-regulation of dynorphin and aspartate was only observed when there was an almost complete denervation of the neostriatum as visualized with antiserum to tyrosine hydroxylase, a marker for dopamine fibres. The present results raise the possibility that aspartate may act as a neurotransmitter released from interneurons in the neostriatum.

Animals↗
PubMed1996

Modulation of neurotransmitter release by cholecystokinin in the neostriatum and substantia nigra of the rat: regional and receptor specificity.

The effect of cholecystokinin peptides on the release of dynorphin B, aspartate, glutamate, dopamine and GABA in the neostriatum and substantia nigra of the rat was investigated using in vivo microdialysis. Sulphated cholecystokinin-8S in the dialysis perfusate (1-100 microM) induced a concentration-dependent increase in extracellular dynorphin B and aspartate levels, both in the neostriatum and substantia nigra. Striatal dopamine levels were only increased by 100 microM of cholecystokinin-8S, while in the substantia nigra they were increased by 10-100 microM of cholecystokinin-8S. Extracellular GABA and glutamate levels were increased following 100 microM of cholecystokinin-8S only. Striatal cholecystokinin-8S administration also produced a significant increase in nigral dynorphin B levels. Local cholecystokinin-4 (100 microM) produced a moderate, but significant, increase of extracellular dynorphin B and aspartate levels in the neostriatum and substantia nigra. No effect was observed on the other neurotransmitters investigated. A 6-hydroxydopamine lesion of the nigrostriatal dopamine pathway did not affect the increases in dynorphin B and aspartate levels produced by local administration of cholecystokinin-8S. Basal extracellular GABA levels were increased significantly in both the neostriatum and substantia nigra ipsilateral to the lesion. Nigral glutamate and aspartate levels were also increased in the lesioned substantia nigra, but in the lesioned neostriatum aspartate levels were decreased. The cholecystokinin-B antagonist L-365,260 (20 mg/kg, s.c.), but not the cholecystokinin-A antagonist L-364,718 (devazepide; 20 mg/kg, s.c.), significantly inhibited the effect of cholecystokinin-8S on striatal dynorphin B and aspartate levels. In the substantia nigra, however, the effect of cholecystokinin-8S on dynorphin B and aspartate levels was inhibited to a similar extent by both L-365,260 and L-364,718. Pretreatment with L-364,718, but not with L-365.260, prevented the increase in nigral dopamine levels produced by nigral cholecystokinin-8S administration. Taken together, these results suggest that cholecystokinin-8S modulates dynorphin B and aspartate release in the neostriatum and substantia nigra of the rat via different receptor mechanisms. In the neostriatum, the effect of cholecystokinin-8S on dynorphin B and aspartate release is mediated via the cholecystokinin-B receptor subtype, while in the substantia nigra, cholecystokinin-8S modulates dynorphin B and aspartate release via both cholecystokinin-A and cholecystokinin-B receptor subtypes. Cholecystokinin-8S modulates dopamine release mainly in the substantia nigra, via the cholecystokinin-A receptor subtype.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Studies of the molecular basis of IgA production, subclass regulation and class-switch recombination in IgA nephropathy patients.

IgA nephropathy (IgAN), the most common form of glomerulonephritis, is characterized by normal to elevated levels of serum IgA. In order to understand the molecular mechanism(s) involved in the production of IgA in IgAN, peripheral blood mononuclear cells (PBMC) from these patients were analysed in this study. IL-10, transforming growth factor-beta 1 (TGF-beta 1) and CD40 have previously been shown to be involved in IgA production. We show here that CD40L expression was increased three-fold in these patients. However, expression of TGF-beta 1 in serum levels was comparable to controls. In vitro stimulation of PBMC with a polyclonal activator resulted in a three-fold increase in synthesis of both IgA subclasses, with a preference for IgA1 RNA. In situ hybridization studies also showed a three-fold increase in the numbers of IgA1- and IgA2-producing cells, but the subclass distribution was similar to the controls. Furthermore, using the nested primer polymerase chain reaction (PCR) for amplifying switch (S mu/S alpha) breakpoints we could demonstrate that in unstimulated PBMC the switch frequency did not differ from that of control donors. Sequence analysis of the amplified switch breakpoints and the I alpha regulatory region from patients showed no structural abnormality. Although we have previously demonstrated a correlation to in vivo germ-line RNA expression and class switching, no I alpha transcripts were detected in unstimulated PBMC from these patients. However, stimulation of PBMC with TGF-beta 1 resulted in I alpha production. Taken together, results from in vivo and in vitro studies suggest that increased cytokine production and hyperresponsiveness to polyclonal stimulation may play an important role in the increased synthesis of IgA. The preference for IgA1 is due to increased production of IgA1 per cell, and the absence of I alpha RNA indicates that additional defect(s) in immune regulation may play an important role in the pathogenesis of IgAN.

Adolescent↗
PubMed1996

On the origin of extracellular glutamate levels monitored in the basal ganglia of the rat by in vivo microdialysis.

Several putative neurotransmitters and metabolites were monitored simultaneously in the extracellular space of neostriatum, substantia nigra, and cortex and in subcutaneous tissue of the rat by in vivo microdialysis. Glutamate (Glu) and aspartate (Asp) were at submicromolar and gamma-aminobutyric acid (GABA) was at nanomolar concentrations in all brain regions. The highest concentration of dopamine (DA) was in the neostriatum. Dynorphin B (Dyn B) was in the picomolar range in all brain regions. Although no GABA, DA, or Dyn B could be detected in subcutaneous tissue, Glu and Asp levels were 5 and approximately 5 and approximately 0.4 microM, respectively. Lactate and pyruvate concentrations were approximately 200 and approximately 10 microM in all regions. The following criteria were applied to ascertain the neuronal origin of substances quantified by microdialysis: sensitivity to (a) K+ depolarization, (b) Na+ channel blockade, (c) removal of extracellular Ca2+, and (d) depletion of presynaptic vesicles by local administration of alpha-latrotoxin. DA, Dyn B, and GABA largely satisfied all these criteria. In contrast, Glu and Asp levels were not greatly affected by K+ depolarization and were increased by perfusing with tetrodotoxin or with Ca2+-free medium, arguing against a neuronal origin. However, Glu and Asp, as well as DA and GABA, levels were decreased under both basal and K+-depolarizing conditions by alpha-latrotoxin. Because the effect of K+ depolarization on Glu and Asp could be masked by reuptake into nerve terminals and glial cells, the reuptake blocker dihydrokainic acid (DHKA) or L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) was included in the microdialysis perfusion medium. The effect of K+ depolarization on Glu and Asp levels was increased by DHKA, but GABA levels were also affected. In contrast, PDC increased only Glu levels. It is concluded that there is pool of releasable Glu and Asp in the rat brain. However, extracellular levels of amino acids monitored by in vivo microdialysis reflect the balance between neuronal release and reuptake into surrounding nerve terminals and glial elements.

Amino Acids↗
PubMed1996

Methylsulfonyl metabolites of PCBs and DDE in human milk in Sweden, 1972-1992.

A multicomponent method used for analysis of organochlorine pesticides, polychlorinated biphenyls (PCBs), naphthalenes, dibenzo-p-dioxins, and dibenzofurans was adapted for the analysis of methylsulfonyl metabolites of chlorinated biphenyls (MeSO2-CBs) and of p,p'-DDE (MeSO2-DDE) in human milk. The extraction and initial purification was made by liquid-gel partitioning. Additional purification and separation steps were achieved by adsorption and gel permeation chromatography. The mean recoveries of 23 MeSO2-CBs and MeSO2-DDE standards, added to the milk before extraction, were 80-97%. Human milk sampled in Stockholm during 1972, 1976, 1980, 1984/85, 1990, 1991, and 1992 was analyzed by GC-MS. During the time course studied, the concentrations of MeSO2-CBs decreased from approximately 9 to 2 ng/g lipids and of MeSO2-DDE from 5 to 0.4 ng/g lipids. The concentrations of MeSO2-CBs and MeSO2-DDE correlated to the levels of total PCB and p,p'-DDE, respectively. 3-MeSO2-DDE was the major isomer of the aryl methyl sulfones studied in the milk. PCB methyl sulfones with five and six chlorine atoms in the molecule were predominant among the PCB methyl sulfones Generally, the concentrations of 4-MeSO2-CBs were higher than the corresponding 3-MeSO2-CB compound. The major MeSO2-CBs in the milk were 4-MeSO2-2,5,2',3',4'-pentaCB (4-87) and 4-MeSO2-2,3,6,2',4',5'-hexaCB (4-149).

Female↗
PubMed1995

Studies of four novel diphenylbutylpiperazinepyridyl derivatives on release and inhibition of reuptake of dopamine, serotonin and noradrenaline by rat brain in vitro.

Four novel diphenylbutylpiperazinepyridyl derivatives (FG5865 (2-[4-[4,4-bis(4-fluorophenyl)butyl]-1-piperazinyl]-3-pyridine- carboxamide), FG5891 (2-[4-[4,4-bis(4-fluorophenyl)butyl]-1-piperazinyl]-N-methyl-3- pyridinecarboxamide), FG5893 (2-[4-[4,4-bis(4-fluorophenyl)butyl]-1-piperazinyl]-3- pyridinecarboxylic acid methyl ester) and FG5909 (2-[4-[4,4-bis(4-fluorophenyl)butyl]-1-piperazinyl]-3-hydroxypyridine) were tested concerning their effects on in vitro release and reuptake of neurotransmitters. Serotonin, noradrenaline and dopamine were those considered, with rat synaptosomes prepared respectively from frontal cortex, cortex and striatum. FG5865, FG5891, FG5893 and FG5909 were found to potently inhibit the uptake of all three neurotransmitters. In addition, FG5865, FG5891 and FG5893 increased the release of serotonin and dopamine from perfused frontal cortical and striatal tissue; FG5865 was most potent in this regard. The release induced by the FG compounds was, however, much less than that induced by e.g. fenfluramine or amphetamine. All four FG compounds were also found to inhibit glutamate-stimulated release of dopamine from striatal tissue; for FG5893 this inhibition occurred at nanomolar concentrations.

Animals↗
PubMed1995

Effect of local cholecystokinin-8 administration on extracellular levels of amino acids and glycolytic products monitored by in vivo microdialysis in the fronto-parietal cortex of the rat.

The effects of local cholecystokinin-8 (CCK-8) administration on cortical extracellular levels of amino acids, catecholamines and metabolism products were studied in the halothane anaesthetized rat by in vivo microdialysis. CCK-8 (10 microM), administrated via a microdialysis probe, produced a significant increase in the levels of aspartate, glutamate and gamma-aminobutyric acid (GABA), but not of 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), lactate and pyruvate, which were simultaneously monitored. The increase in aspartate and glutamate levels produced by CCK-8 was about 3-4-fold. The effect of CCK-8 on aspartate levels was significantly inhibited by the CCKB antagonist, L-365,260 (20 mg kg-1, s.c.), but not by the CCKA antagonist, L-364,718 (20 mg kg-1, s.c.). In contrast, the increase in glutamate levels was inhibited by both L-365,260 and L-364,718. GABA was slightly, but significantly increased (approximately 30%), by local CCK-8 and was inhibited by both CCK antagonists. The present results show that CCK-8 exerts a strong modulatory action on both aspartate and glutamate release in rat cortex. While the effect of CCK-8 on aspartate is selectively mediated via CCKB receptor subtype, the effect of CCK-8 on glutamate appears to be mediated via both CCKA and CCKB receptor subtypes.

Amino Acids↗
PubMed1995

Hypertension two years after renal transplantation: causes and consequences.

The incidence of hypertension 2 years after renal transplantation and the possible causes of hypertension were studied retrospectively. A group of 93 patients treated with cyclosporin (CyA), azathioprine (Aza), and/or prednisolone (Pred) were compared to a group of 31 patients treated with Aza and Pred. There were more patients with hypertension in the CyA group (73%) than in the Aza group (58%). Hypertension before transplantation predisposed to hypertension after transplantation. After transplantation, hypertension was most common among patients with polycystic kidney disease (46%), chronic glomerulonephritis (67%), and diabetes (71%). The accumulated immunosuppressive medication (CyA/Pred) did not affect the occurrence of hypertension. Hypertensive patients had significantly poorer graft function than did normotensive patients (serum creatinine level 229 mumol/l vs 162 mumol/l, P < 0.01). The 10-year graft survival was markedly impaired in the group with hypertension (42% vs 65% for normotensives, P < 0.05). The 10-year patient survival was 59% vs 79% (P = NS). The study further confirms the frequent finding that hypertension has a negative effect on graft and patient survival rates.

Adult↗
PubMed1995

Blood pressure and renal function seven years after pregnancy complicated by hypertension.

OBJECTIVE: To assess the occurrence of chronic hypertension and renal disorder after gestations complicated by pregnancy induced hypertension or pre-eclampsia and to define background factors and laboratory analyses at follow up examination which discriminate between women who remain normotensive and those who develop hypertension. SETTING: Swedish university hospital. SUBJECTS: Women with pregnancy induced hypertension (PIH) (n = 49), pre-eclampsia (n = 45) or a normotensive pregnancy (n = 44) during 1986. DESIGN: Subjects were reviewed in 1993 with regard to chronic hypertension and renal disorder. Plasma concentrations of creatinine, urea, uric acid, calcium and albumin were measured, and urine was examined for the presence of microalbuminuria and erythrocyte excretion rate. Those with and without hypertension at follow up were compared with regard to the renal function tests and possible features in the history which might predict chronic hypertension. RESULTS: Women with a history of pregnancy induced hypertension or pre-eclampsia had an increased risk, relative to controls, for hypertension at follow up (37% and 20% vs 2%; P < 0.001), microalbuminuria (14% and 20% vs 2%; P < 0.05) and demonstrated increased plasma levels of albumin corrected calcium (2.41 [SE 0.02] and 2.40 [0.01] vs 2.32 [0.01] mmol/l; P < 0.001). The only factors significantly associated with hypertension at follow up were the presence of microalbuminuria (P = 0.0008) and having had a delivery prior to the index pregnancy (P = 0.0017). CONCLUSIONS: The risk for chronic hypertension seven years after a pregnancy complicated with pregnancy induced hypertension or pre-eclampsia is considerably increased. The presence of hypertension at follow up is closely related to residual renal disorder.

Adult↗
PubMed1994

Modulation of striatal aspartate and dynorphin B release by cholecystokinin (CCK-8) studied in vivo with microdialysis.

Sulphated cholecystokinin-8 (CCK-8) given into the neostriatum of the rat by in vivo microdialysis produced a concentration-dependent (1-100 microM) increase in extracellular aspartate (Asp) and dynorphin B (Dyn B), but not in glutamate, GABA or dopamine levels. The increase in Asp levels produced by 10 microM CCK-8 was approximately 10 fold and was inhibited (approximately 50%) by the CCKB antagonist L-365,260 (20 mg kg-1, i.p.), while the increase in Dyn B (approximately 2 fold) was totally abolished. Both increases were inhibited (approximately 50%) by local infusion of 10 microM of tetrodotoxin (TTX). Thus, CCK exerts modulatory effects in the basal ganglia, possibly by interacting with local neostriatal neurones releasing Asp, and with Dyn B-containing neurones projecting to the pars reticulata of the substantia nigra.

Animals↗
PubMed1994

Effect of microwave radiation on permeability of liposomes. Evidence against non-thermal leakage.

The effect of 2.45 GHz microwave radiation on the permeability of unilamellar phosphatidylcholine liposomes has been studied. Leakage of 5(6)-carboxyfluorescein from the liposomes was measured using spectrofluorimetry after exposure to either microwaves or thermal heating for 5-20 min intervals. The exposure temperature, 37.6 +/- 0.5 degrees C, was well above the phase transition temperature of the lipid membrane. The microwave exposure did not result in any non-thermal increase in permeability above that produced by thermal heating. This study refutes the results reported by Saalman et al. [1] in which an increased liposome permeability due to microwave exposure was reported. The refined analysis in the present study shows that this increased liposome permeability was not a non-thermal microwave effect.

Fluoresceins↗