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B I Gustafsson

Publications and source records attributed to B I Gustafsson.

At least 19 recordsLinked to original sources
PubMed2007

Long-term fluoxetine administration does not result in major changes in bone architecture and strength in growing rats.

Many studies have indicated that serotonin and its transporter play a role in bone metabolism. In this study we investigated the effect of selective serotonin re-uptake inhibitor (SSRI), fluoxetine (Prozac) on bone architecture and quality in growing female rats. We therefore administrated rats with clinically relevant doses of fluoxetine for a period of 6 months. DXA scans were performed during the treatment period in order to follow parameters as body weight, fat percentage and BMD. After 6 months of treatment, femurs were used to analyze bone architecture and bone strength, by means of microCT scans and three-point bending assays, respectively. We found a slightly diminished bone quality, reflected in a lower bone tissue strength, which was compensated by changes in bone geometry. As leptin and adiponectin could be possible factors in the serotonergic regulation of bone metabolism, we also determined the levels of these factors in plasma samples of all animals. Leptin and adiponectin levels were not different between the control group and fluoxetine-treated group, indicating that these factors were not involved in the observed changes in bone geometry and quality.

Adiponectin↗
PubMed2006

Serotonin and fluoxetine modulate bone cell function in vitro.

Recent studies have proposed a role for serotonin and its transporter in regulation of bone cell function. In the present study, we examined the in vitro effects of serotonin and the serotonin transporter inhibitor fluoxetine "Prozac" on osteoblasts and osteoclasts. Human mononuclear cells were differentiated into osteoclasts in the presence of serotonin or fluoxetine. Both compounds affected the total number of differentiated osteoclasts as well as bone resorption in a bell-shaped manner. RT-PCR on the human osteoclasts demonstrated several serotonin receptors, the serotonin transporter, and the rate-limiting enzyme in serotonin synthesis, tryptophan hydroxylase 1 (Tph1). Tph1 expression was also found in murine osteoblasts and osteoclasts, indicating an ability to produce serotonin. In murine pre-osteoclasts (RAW264.7), serotonin as well as fluoxetine affected proliferation and NFkappaB activity in a biphasic manner. Proliferation of human mesenchymal stem cells (MSC) and primary osteoblasts (NHO), and 5-HT2A receptor expression was enhanced by serotonin. Fluoxetine stimulated proliferation of MSC and murine preosteoblasts (MC3T3-E1) in nM concentrations, microM concentrations were inhibitory. The effect of fluoxetine seemed direct, probably through 5-HT2 receptors. Serotonin-induced proliferation of MC3T3-E1 cells was inhibited by the PKC inhibitor (GF109203) and was also markedly reduced when antagonists of the serotonin receptors 5-HT2B/C or 5-HT2A/C were added. Serotonin increased osteoprotegerin (OPG) and decreased receptor activator of NF-kappaB ligand (RANKL) secretion from osteoblasts, suggesting a role in osteoblast-induced inhibition of osteoclast differentiation, whereas fluoxetine had the opposite effect. This study further describes possible mechanisms by which serotonin and the serotonin transporter can affect bone cell function.

3T3 Cells↗
PubMed2006

Retransplantation of the liver.

Retransplantation (re-TX) is the only available therapy for irreversible liver graft dysfunction. The outcome of a second procedure depends upon several factors, some of which are not defined at the time of the decision to retransplant. This study is an analysis of all re-TX of the liver performed at our unit between January 1995 and January 2004. Among the 474 liver TX were 55 (11.6%) re-TX in 47 patients. We studied (1) diagnosis at first TX; (2) indication for re-TX and time lapse; (3) donor age and cold ischemia time (CIT); (4) duration of operation, peroperative bleeding, and complications; (5) ICU and ward periods; and (6) patient and graft survivals. Patients who underwent re-TX did not differ from those transplanted once with regard to age, gender, or diagnosis. The indications for re-TX were roughly one-third biliary tract complications/chronic rejection, one-third hepatic artery thrombosis, and one-third others, including primary nonfunction, acute rejection, portal vein thrombosis, sepsis, and B/C hepatitis. The re-TX were "urgent" in 29 and "elective" in 26 cases. Complications were common; about half of the patients were reoperated due to bleeding or biliary problems. To date (May 2004), 15 patients have died (12 "urgent" and 3 "elective"), of whom 5 had well functioning grafts. In summary, liver re-TX is a complicated procedure associated with significant mortality and morbidity, but considering that the actual patient group has a poor prognosis without re-TX, the results are nevertheless encouraging.

Adolescent↗
PubMed2006

Pharmacological preconditioning of rat liver by up-regulation of heme oxygenase 1.

PURPOSE: We investigated whether pharmacologically induced up-regulation of heme oxygenase 1 by pyrrolidine dithiocarbamate (PDTC) conferred protection against subsequent ischemia-reperfusion injury (IRI) to the rat liver after temporary vascular occlusion of 70% of the organ. METHODS: Female Wistar rats (200 to 250 g body weight) anesthetized with pentobarbitone were cannulated in the carotid artery and jugular vein. After laparotomy, a rubber band was applied around the entire vascular supply to the median and left lateral lobes, enabling vascular occlusion of 70% of the liver. A laser Doppler miniprobe was placed on the left lateral lobe to monitor peripheral liver blood flow (PLBF). Immediately upon completion of the surgery, the rats were administered either PDTC (50 mg/kg intravenously; n = 8) or its solvent (isotonic NaCl; n = 8). After 60 minutes, regional ischemia was induced for 30 minutes. The animals were then monitored for 2 hours of reperfusion. Blood samples for alanine transferase (ALT) estimation (as a measure of parenchymal injury) were drawn immediately prior to ischemia and reperfusion, as well as 60 and 120 minutes after reperfusion; PLBF was calculated at these times. RESULTS: ALT increased in the course of the experiments but there was no difference between the groups. The reduction in PBLF due to ischemia-reperfusion was significantly lower in the PDTC group: about 16% versus 40%, after 2 hours of reperfusion. CONCLUSION: Pretreatment with PDTC attenuated the disturbance of hepatic microcirculation, but not parenchymal injury, in the early phase of IRI.

Alanine Transaminase↗
PubMed2006

Increase in organ donation rate in a Swedish region after implementing a new angle of approach.

In the Swedish Västra Götaland region (1.65 million inhabitants), we have implemented, as from January 1, 2006, a new concept to improve the organ donation rate, which in 2005 was 13.9 per million population (PMP). There are two cornerstones in the project: a new, active role for the transplant coordinators and the establishment of a uniform policy for the care of potential donors as well as criteria for the decision to offer intensive care in various critical conditions. The coordinator is now contacted at an early stage and is in place when the brain death diagnosis is underway or completed. The coordinator is thereafter a resource for all aspects of the care of the potential donor/donor, and also in the contact with the relatives. To date (May 2006) the donation rate has reached 23.6 PMP annually (a 70% increase).

Adolescent↗
PubMed2006

Effect of remote preconditioning on mild or severe ischemia-reperfusion injury to rat liver.

UNLABELLED: In this study we examined the effect of remote ischemic preconditioning (RIPC) on liver ischemia-reperfusion (IR) injury. Anesthetized Wistar rats (200 to 250 g body weight, n = 32) had the right femoral artery (FA) dissected. Protocol I. The hepatic artery (HA) was clamped for 60 minutes; peripheral liver blood flow (PLBF) and alanine aminotransferase (ALT) were measured prior to clamping as well as 60 minutes after reperfusion. The cohorts were group 1 (no RIPC; n = 10) and group 2 (RIPC; n = 10) 35 minutes after surgery, the FA was clamped for 10 minutes. After 15 minutes, the HA was clamped as in group 1. In protocol II, a rubber band was applied around the entire vascular supply to about 70% of the liver, yielding group 3 (no RIPC; n = 6) that 60 minutes after surgery, had vascular occlusion performed for 30 minutes and group 4 (RIPC; n = 6) with the FA clamped as above, in a procedure otherwise identical to that of group 3. RESULTS: In protocol I, there was no significant difference in PLBF between the two groups after reperfusion, but the increased ALT levels in the RIPC group were reduced (.70 +/- .05 vs. 1.0 +/- .15 microkat/L, P = .049). In protocol II, we observed no significant differences in ALT levels or PLBF between the two groups. Thus, a beneficial effect of RIPC was demonstrated in protocol I with relative hypoxemia to the liver. However, the effect could not be demonstrated in protocol II, which induced a more severe IR injury.

Alanine Transaminase↗
PubMed2005

Nitric oxide-mediated effects on liver blood flow.

We investigated whether blockade of nitric oxide synthase by the arginine analog l- NAME could affect peripheral liver blood flow (PLBF) or hepatocyte integrity (serum ALT) in either a control series or in a series subjected to mild reduction of liver blood flow by temporary clamping of the hepatic artery (HA). Anesthetized rats were arranged for mean arterial pressure (MAP) recordings via a carotid artery, drug injections, and blood sampling via a jugular vein, and monitoring of PLBF using a laser Doppler flowmeter. In series 1, the rats received either l-NAME (30 mg/kg i.v.) or NaCl. l-NAME caused a significant decrease in PLBF and an increase in MAP compared to NaCl; ALT did not differ. In series 2, l-NAME (30 mg/kg i.v.) or NaCl was administered at the beginning of the experiment. After 60 minutes of equilibration, the HA was clamped for 60 minutes then unclamped for another 60 minutes. As in series 1, the l-NAME group had significantly lower PLBF and higher MAP than the NaCl group. Occlusion of the HA resulted in significantly greater reduction in PLBF in the NaCl versus the l-NAME group. Upon unclamping, there was no difference in ALT levels, PLBF, or MAP. To conclude, NO displayed a positive tonic effect on liver blood flow, reduction of which with l-NAME did not aggravate mild ischemia/reperfusion injury in this model.

Animals↗
PubMed1994

Vagal influence on the motility of the feline jejunum.

1. The effects of electrical stimulation of the peripheral end of the cervical vagal nerve on jejunal motility were investigated in anaesthetized cats, pretreated with guanethidine, with sectioned splanchnic nerves and ligated adrenal vessels. Motility was monitored as volume changes of an intraluminal balloon. 2. Vagal stimulation elicited frequency-dependent hypermotility with a short latency. Relaxatory events were also observed, which could indicate the presence of a non-adrenergic inhibitory pathway. 3. After atropine treatment, contractions and relaxations could still be elicited. The former were compared to cholinergic contractions and showed a lower maximal amplitude and a longer latency to onset. Moreover, they were antagonized by 80-100% by the opioid receptor antagonist, naloxone. 4. Vagal stimulation after hemicholinium, given in order to deplete the preganglionic acetylcholine content, elicited naloxone-sensitive contractions. This suggests that a subpopulation of the vagal preganglionic fibres is non-cholinergic. 5. Isolation of the balloon-containing segment did not qualitatively alter the responses, indicating that the vagal fibres reach the small intestine via the paravascular mesenteric nerves. 6. It is concluded that cholinergic and non-adrenergic, non-cholinergic (NANC) contractions, as well as relaxations, could be elicited by efferent vagal stimulation. The NANC contractions seem to result from the activation of opioid receptors causing disinhibition of a tonic neurogenic restraint on the gut muscle.

Animals↗
PubMed1994

Neurogenic inhibition of duodenal and jejunal motility in the anaesthetized rat.

Duodenal or jejunal motility (monitored as pressure changes in a saline-perfused intraluminal catheter) was studied in anaesthetized rats, vagotomized and pretreated with adrenergic blocking agents. In the duodenum (but not the jejunum), atropine or the selective muscarinic M1 and M3 receptor antagonists, pirenzepine and 4-diphenyl-acetoxy-N-methylpiperidine (4-DAMP), respectively, augmented the spontaneous contractile activity. This effect could be abolished either by nicotinic ganglionic receptor antagonism with hexamethonium, or with morphine. Moreover, blockade of the synthesis of nitric oxide by N omega-nitro-L-arginine elicited hypermotility both in the duodenum and the jejunum, and also this response was abolished by hexamethonium. It is proposed from the present results that the rat small is controlled by non-adrenergic, non-cholinergic inhibitory as well as excitatory motor neurons. The latter motor neurons seem to be modulated by muscarinic, nitroxergic or opioidergic mechanisms.

Animals↗
PubMed1993

Motor effects of indomethacin, morphine or vagal nerve stimulation on the feline small intestine in vivo.

Some factors known to affect jejunal motility (recorded as volume changes of an intraluminal balloon) were investigated in anaesthetized cats (ether-chloralose) pretreated with guanethidine and atropine. Indomethacin, morphine (both compounds administered systemically) or vagal nerve stimulation elicited jejunal excitatory motor responses. The effect of indomethacin seemed to be independent of cyclooxygenase inhibition and probably did not involve opioid receptors. It is suggested that the spasmogenic stimuli caused jejunal hypermotility by inhibiting tonically active, inhibitory motor neurons that are intrinsic to the gut. Furthermore, when the jenunal tone had been raised by indomethacin or morphine spontaneous relaxations were observed, and these could be mimicked by vagal stimulation. Hexamethonium antagonized these relaxations but did not attenuate the drug-induced jejunal hypermotility.

Animals↗
PubMed1988

Effects of indomethacin on non-adrenergic, non-cholinergic motility of stomach and small intestine.

Stimulation of the sectioned cervical vagal nerve of anaesthetized cats (ether-chloralose), pretreated with guanethidine and atropine, in the peripheral direction produced gastric relaxation as well as jejunal and ileal contraction. The administration of indomethacin markedly enhanced intestinal tone and the amplitude of spontaneous phasic activity while the basal gastric motility was essentially unchanged. This suggests that endogenous prostaglandins exert an inhibitory influence on intestinal motility. The vagally induced gastric relaxation was significantly inhibited by indomethacin, with could suggest that prostaglandins modulate non-adrenergic, non-cholinergic inhibitory neurotransmission in the stomach.

Animals↗
PubMed1988

Motor responses elicited by local electrical stimulation of the distal colon in the anaesthetized rat.

A method to study electrically induced distal colonic motility in the rat in vivo is reported. The animals were anaesthetized with methohexital and chloralose and were artificially ventilated. Motility of a segment (2 cm) of the distal colon was monitored as volume changes of an intraluminal balloon, introduced via the anus. Local electrical stimulation of the wall of the segment was achieved by means of a bipolar electrode folded around the gut. Stimulations produced reproducible contractile responses in a frequency dependent fashion. Stimulation characteristics resembled those of other autonomic neuro-effector systems. The adrenergic neuron-blocker, guanethidine, significantly lowered colonic tone, but had no other effects on spontaneous or electrically induced motility. Atropine significantly lowered colonic tone. After the administration of this compound the electrically induced contractions were significantly smaller with a shorter duration and, furthermore, appeared upon the cessation of stimulation ('off' or 'rebound' contraction). Following the administration of tetrodotoxin (TTX, given close i.a. via a cannula with its tip in distal aorta) basal colonic tone and the number of spontaneously occurring contractions increased. The amplitude and duration of the electrically induced responses were significantly attenuated and, furthermore, appeared as 'rebound' contractions which were preceded by a relaxation. Such TTX-resistant responses may be myogenic, but a neurogenic origin cannot be excluded. The present study showed that local electrical stimulation of the distal colon elicits cholinergic contractions, but also atropine- and TTX-resistant motor responses.

Animals↗
PubMedDate not supplied

Tonic inhibition of small intestinal motility by nitric oxide.

The effects of blocking nitric oxide synthase with the arginine analog N omega-nitro-L-arginine (L-NNA) were investigated in anaesthetized cats, vagotomized and pretreated with guanethidine and atropine. Spontaneous NANC jejunal motility (recorded as the volume changes of an intraluminal balloon) was markedly increased in a dose-dependent and stereospecific manner. The effect of L-NNA was partly reversed by L-arginine, the substrate for nitric oxide (NO) synthesis. Thus, this study presents evidence for a tonic inhibitory influence, via the release of NO, on small intestinal motility in vivo. Furthermore, relaxations upon the L-NNA-induced hypermotility could be elicited by vagal nerve stimulation, which may suggest the existence of another NANC inhibitory transmitter. Hexamethonium abolished such relaxations but did not affect the tone or phasic activity after L-NNA.

Amino Acid Oxidoreductases↗