Prevention of ski injuries.
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Biomedical subjects
Publications and source records attributed to E Eriksson.
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The abilities of dopamine (DA) and the partial DA D2 receptor agonist (-)-(3-hydroxyphenyl)-N-n-propylpiperidine, (-)-3-PPP, to suppress prolactin (PRL) release induced by any of five different PRL secretagogues in GH4C1 cells transfected with the human D2 receptor (short isoform) were investigated. Whereas DA reduced the response to all five secretagogues. (-)-3-PPP reduced the response to vasoactive intestinal peptide (VIP) and thyrotropin-releasing hormone (TRH), but not to high medium potassium (K+) or to the potassium channel antagonist tetraethylammonium (TEA). (-)-3-PPP tended to reduce the PRL release induced by the Ca2+ channel agonist BAY K-8644 (BAY); however, this effect of the partial agonist was modest and not significant. Whereas the effects of both DA and (-)-3-PPP on the PRL response to VIP and TRH were counteracted by co-incubation with the D2 antagonist raclopride, the effects of DA on the PRL response to K+, BAY, and TEA were antagonized by co-incubation with either raclopride or (-)-3-PPP. The results show that, at a given receptor density, the intrinsic activity of a partial D2 agonist with respect to D2-mediated suppression of PRL release may vary from agonism to antagonism depending on which intracellular transduction systems that are being concomitantly activated.
A male rat put in an open-field arena in which it is free to spend time in the vicinity of--but not in contact with--an estrous female, or in the vicinity of a male, usually spends more time with the female than with the male or elsewhere. Tentatively, the percentage of time spent in the vicinity of the female in this paradigm may be regarded as a measure of sexual motivation. In humans, treatment with selective serotonin reuptake inhibitors (SSRIs) may cause reduced libido. To investigate to what extent serotonin reuptake inhibition influences sexual motivation also in rats, we have tested the effect of subchronic treatment with fluoxetine on the behavior in the sexual motivation test described above; in addition, the effect of fluoxetine on male copulatory behavior was studied. Fluoxetine significantly reduced sexual motivation at subchronic but not at acute administration; moreover, fluoxetine-treated rats displayed an increased ejaculation latency. It is concluded that humans and rats respond similarly to the SSRI fluoxetine with respect to various aspects of sexual behavior.
Treatment with serotonin reuptake inhibitors (SRIs) has been shown to cause reduced libido and anorgasmia in women. A large body of evidence suggests that serotonin may influence sexual behavior in estradiol + progesterone primed, gonadectomized female rats; however, the influence of selective SRIs on the estrous behavior of intact female rats has not been described previously. In the present study, the effect of 1 to 3 weeks of fluoxetine administration (10 mg/kg daily) on vaginal and behavioral estrus in intact female rats was studied; in addition, the effect of fluoxetine (same dose, 1-8 weeks) on copulatory behavior and on sexual motivation in hormone-primed gonadectomized rats was investigated. Subchronic administration of fluoxetine did not influence cyclicity as judged by the examination of vaginal smears but significantly reduced the percentage of rats displaying receptive behavior in the estrous phase. In addition, fluoxetine significantly reduced receptive behavior, including lordosis, in ovariectomized female rats primed with estradiol (6.25 micrograms/rat; -48 hr) plus progesterone (1.0 mg/rat, -4 hr); in contrast, sexual motivation--as reflected by the amount of time these rats elected to spend in the vicinity of a male rather than in the vicinity of a female or elsewhere--was little affected by the treatment.
Male rats exposed to high levels of testosterone for 8 weeks, or to one high dose of testosterone 24 h before testing, displayed an increase in punished responding in the Vogel conflict test. The findings may be taken as indirect support for the assumption that the conflict paradigm reflects not only anxiety but also impulsivity.
In CHO cells transfected with the rat dopamine D2 receptor (long isoform), administration of dopamine per se elicited a concentration-dependent increase in arachidonic acid (AA) release. The maximal effect was 197% of controls (EC50=25 nM). The partial D2 receptor agonist, (-)-(3-hydroxyphenyl)-N-n-propylpiperidine [(-)-3-PPP], also induced AA release, but with somewhat lower efficacy (maximal effect: 165%; EC50=91 nM). The AA-releasing effect of dopamine was counteracted by pertussis toxin, by the inhibitor of intracellular Ca2+ release, 8-(N N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), by excluding calcium from the medium, by the phospholipase A2 (PLA2) inhibitor, quinacrine, and by long-term pretreatment with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). In addition, it was antagonized by the D2 antagonists, raclopride and (-)-sulpiride--but not by (+)-sulpiride--and absent in sham-transfected CHO cells devoid of D2 receptors. The results obtained contrast to the previous notion that dopamine and other D2 receptor agonists require the concomitant administration of calcium-mobilizing agents such as ATP, ionophore A-23187 (calcimycin), thrombin, and TRH, to influence AA release from various cell lines.
BACKGROUND: Postoperative adhesion formation has been associated with a decreased capacity to degrade intra-abdominally deposited fibrin. Adhesions, once lysed, have a high propensity for reformation. This study tested the hypothesis that patients with a high propensity for adhesion formation as well as adhesion tissue had a reduced fibrinolytic capacity. METHODS: Peritoneal biopsies were taken during abdominal surgery from 21 patients who had previously undergone operation; previously formed adhesion tissue was sampled from ten of these patients. Adhesion formation was scored. The fibrinolytic capacity of peritoneum was determined in tissue extracts. RESULTS: At the time of opening of the abdominal cavity, levels of plasminogen activator inhibitor (PAI) type 1 (P = 0.009) and tissue-type plasminogen activator (tPA)/PAI complex (P = 0.008) were increased in peritoneal samples from patients with severe adhesions compared with those in samples from patients with less severe adhesions. Adhesion tissue similarly had reduced fibrinolytic capacity as judged by a decrease in tPA activity (P = 0.005) and an increase in PAI-1 level (P = 0.01), reflected in an increased level of tPA/PAI complex (P = 0.008) compared with unaffected peritoneum. CONCLUSION: These observations demonstrate reduced fibrinolytic capacity in peritoneal tissue in patients with a greater propensity for development of adhesions and likewise in adhesion tissue. This suggests that components of the fibrinolytic system may be used as markers of an increased risk of adhesion development.
BACKGROUND: Peritoneal fibrinolytic capacity decreases during abdominal operation. This may be a local effect or a part of a generalized response to the procedure. METHODS: Plasma and paired peritoneal biopsy specimens were taken at intervals during abdominal operation, and fibrinolytic components were assayed in plasma and tissue extracts. Values are given as median [interquartile range]. RESULTS: In peritoneal tissue there was a gradual decrease of tissue-type plasminogen activator (tPA) activity, and at 90 minutes of the operation differed significantly from that of the initial sample (1.0 [1.0] ng/mg protein, and 5.1 [6.5] ng/mg protein, respectively, p < 0.05). The tPA activity levels at the wound were significantly lower (1.0 [1.0] ng/mg protein) at 90 minutes compared with a remote peritoneal site (1.8 [1.9] ng/mg protein, p < 0.05). At the wound, the tPA activity correlated significantly with time (r = -0.48, n = 26, p < 0.01). tPA activity and antigen peaked in plasma at 30 minutes (p < 0.05) and 60 minutes (p < 0.05), respectively. Plasminogen activator inhibitor type 1 activity increased in plasma during operation (p < 0.05), but was not detectable in peritoneal samples. CONCLUSIONS: The intraoperative changes in tissue tPA activity were not consistently reflected in plasma samples. These findings suggest that the reduction in peritoneal fibrinolysis during abdominal operation is a local response to trauma.
Thrombin can regulate the-fibrinolytic system by increasing the endothelial production of both tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1). The thrombin receptor transducts signals through the GTP-binding protein system, the classical pathway being the Galpha q-protein. The purpose of the present study was to examine the roles of Galpha i-protein and tyrosine kinases in the thrombin signal transduction of t-PA and PAI-1 production from human adult vein endothelial cells (HAVEC). t-PA and PAI-1 antigen were analysed in conditioned medium from cultured HAVEC after 16 h incubation. Data are expressed as percentages of basal release (100%), means +/- 95% confidence intervals. Thrombin increased t-PA and PAI-1 production (234 +/- 42% and 211 +/- 42%, respectively). Pertussis toxin (PTX) (inhibiting Galpha i-pathway) reduced basal PAI-1 (66 +/- 8%), but had only a weak influence on basal t-PA production. Pertussis toxin and genistein (inhibiting tyrosine kinase) significantly reduced the thrombin induction of both t-PA and PAI-1 (PTX: 142 +/- 23% and 146 +/- 19%, respectively, genistein: 156 +/- 42% and 76 +/- 24%, respectively). The present study demonstrated that thrombin can increase the production of t-PA and PAI-1 by transducting signals through the Galpha i and tyrosine kinase pathway, in addition to the Galpha q/protein kinase C pathway as has been found previously.
In a double-blind trial, the selective serotonin reuptake inhibitor citalopram was administered to women with severe irritability and/or depressed mood in the luteal but not in the follicular phase of the menstrual cycle (premenstrual dysphoria). Treatment continued for three consecutive menstrual cycles. One group (N = 17 completers) was administered citalopram continuously at a constant dosage (20+/-10 mg/day) throughout the menstrual cycle. A second group (N = 17) also received citalopram continuously throughout the cycle, but at a lower dosage in the follicular phases (5 mg/day) than in the luteal phases (20+/-10 mg/day) (semi-intermittent treatment). A third group (N = 18) received citalopram (20+/-10 mg/day) in the luteal phase only and placebo during the follicular phase (intermittent treatment). A fourth group (N = 17) received placebo throughout the cycles. The side effects of active treatment were generally mild and transient. Intermittent administration of citalopram was clearly more effective than placebo with respect to both reduction in self-rated irritability and self-rated global improvement; it is of interest that intermittent treatment with citalopram also seemed more effective than continuous or semi-intermittent administration of the drug.
Although externally exposed ventricular assist devices are associated with extremely high mortality rates, salvage may be accomplished by early aggressive wound debridement, transposition of a well-perfused autologous tissue (such as omentum), dead space obliteration, and adequate external coverage using vascularized tissue. The temporary suppression rather than the total eradication of the infection should be the goal of these procedures.
BACKGROUND: Sameridine, a new substance with both local anesthetic and opioid effects, was administered intrathecally for the first time to humans, i.e. in patients subjected to arthroscopic knee joint surgery. METHOD: A dose-escalating (10, 15, 20 and 25 mg), open study was performed in 33 patients. Only two patients were included in the 25 mg group. RESULTS: Sameridine provided good quality of surgical anesthesia in all patients except those receiving 10 mg. The maximum level of sensory block, Th5-Th7, was reached within 30 min with a median duration of 3.6-3.9 h. The motor block was more profound with increasing dose, but never lasted longer than the sensory block. The influence on heart rate and blood pressure was minor and atropine and ephedrine were needed in four patients. No clinically significant ECG-changes were detected and no arrhythmias were recorded. Oxygen saturation and respiratory rate did not decrease in a clinically significant way and were not affected by concomitant morphine given i.v. postoperatively. There were few side-effects, the most frequent being mild pruritus (10/33). CONCLUSION: Sameridine provided clinically adequate anesthesia for the patients receiving the doses of 15, 20 and 25 mg. Further studies are needed to evaluate the substance and it is of great interest to clinically investigate the opioid component with respect to postoperative analgesia.
The skin plays a crucial role in protecting the integrity of the body's internal milieu. The loss of this largest organ is incompatible with sustained life. In reconstructive surgery or burn management, substitution of the skin is often necessary. In addition to traditional approaches such as split- or full-thickness skin grafts, tissue flaps and free-tissue transfers, skin bioengineering in vitro or in vivo has been developing over the past decades. It applies the principles and methods of both engineering and life sciences toward the development of substitutes to restore and maintain skin structure and function. Currently, these methods are valuable alternatives or complements to other techniques in reconstructive surgery. This review article deals with the evolution and current approaches to the development of in vitro and in vivo epidermis and dermis.
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The object of this study was to evaluate the effect of androgenization on the extracellular concentrations of serotonin in the amygdala of otherwise intact female rats. One group of animals received one high dose of testosterone (1 mg, s.c.) within three hours after birth, one group received continuous administration of testosterone by means of silicone tubings (50 mm) for approximately 20 days starting at day 40, and one group received testosterone both in the neonatal period and from day 40 and onwards. Assessment of extracellular levels of serotonin in the amygdala was undertaken around day 60 using in vivo microdialysis with HPLC detection; the animals were awake and unrestrained during the microdialysis procedure. Dialysate serotonin concentrations did not differ between the three groups of androgenized animals; however, in all three groups, dialysate levels of serotonin were significantly lower than in controls receiving sesame oil neonatally and empty tubings at day 40. It is suggested that the effects of testosterone on sex-dependent behaviours such as aggression and sexual activity may be at least partly due to a reduction in brain serotonin function.