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Biomedical subjects

E Eriksson

Publications and source records attributed to E Eriksson.

At least 235 records · Page 13Linked to original sources

Anticonflict and rotarod impairing effects of alprazolam and diazepam in rat after acute and subchronic administration.

1. The anticonflict and the rotarod impairing effects of the triazolo-benzodiazepine alprazolam (APZ) and the conventional 1,4-benzodiazepine (BDZ) diazepam (DIZ) were studied in the rat. 2. After acute administration the two drugs displayed approximately equal potency with respect to anticonflict effects in Vogel's conflict test and in Montgomery's conflict test. The results obtained in the former model indicate that also the efficacies of the two drugs are approximately equal. The shapes of the dose response curves obtained in this model differed, however, markedly. Thus, while APZ displayed a wide high efficacy dose-range (0.5-16.0 mg/kg), a maximal effect of DIZ was obtained in a narrow dose-range only (around 4.0 mg/kg). 3. Acutely, APZ was more rotarod impairing than DIZ; total impairment after 2.0 mg/kg of APZ and 3.5 mg/kg of DIZ. 4. After daily treatment with doses producing approximately equal and close to maximal anticonflict effects (APZ 1.25 mg/kg/day; DIZ 3.0 mg/kg/day) tolerance developed to the rotarod impairing (6 days of treatment) and the anticonflict (Vogel's conflict test; 9 days of treatment) effects of both drugs. It appeared, however, as if tolerance was more pronounced to the ataxic/sedative effects (approximately a four-fold rightward shift of the dose-response curve) than to the anticonflict effect (approximately a two-fold shift) of APZ, whereas tolerance developed to about the same extent to the two effects of DIZ (approximately two-fold shifts). 5. In conclusion, for APZ, but not for DIZ, after long-term administration of a dose producing marked anxiolytic-like effects, the relationship anxiolytic-like effect vs. ataxic/sedative effects was altered. These findings offer a tentative explanation to the putative advantage of APZ over conventional BDZs in the treatment of panic disorder.

Alprazolam↗

Increased cerebrospinal fluid levels of endorphin immunoreactivity in panic disorder.

Cerebrospinal fluid (CSF) concentrations of beta-endorphin-like immunoreactivity (END-IR) were determined in 11 female and 6 male patients fulfilling the diagnostic criteria of panic disorder (PD) and in matched controls. Eleven of the PD patients had been taking moderate doses of benzodiazepines (BZD) irregularly without satisfactory effect against the panic attacks while six were totally drug-free. No medication was allowed for at least 24 hours before the lumbar puncture. In six patients a second lumbar puncture was performed after 2 to 3 months of treatment with imipramine or clomipramine. In PD patients, CSF levels of END-IR were significantly higher than in controls. Patients that had been taking BZD had somewhat higher concentrations of END-IR than those taking no medication; however, totally drug-free patients also displayed END-IR levels that were significantly higher than in controls. Although they effected a dramatic reduction of the panic attacks, antidepressants did not influence CSF END-IR concentrations.

Adult↗

Prospective study of concentric and eccentric leg muscle torques, flexibility, physical conditioning, and variation of injury rates during one season of amateur ice hockey.

Twenty-three male ice hockey players in a third division amateur ice hockey team were prospectively studied during the 1987-1988 season. O2 uptake, muscle flexibility, and isokinetic concentric and eccentric leg muscle strength were measured before and after the season. All injuries were recorded by one and the same physician attending all the games: 68 injuries occurred altogether but only six of these led to absence from training or matches. O2 uptake and muscle flexibility were unchanged during the season, but a significant drop of both concentric and eccentric quadriceps and hamstring torques occurred in spite of the fact that the team played two games and trained twice per week during the entire season. No correlation between the fall in muscle strength and the injury rate was found. Although many injuries occur in ice hockey, the majority are minor ones that do not lead to absence from playing.

Adult↗

Local proteolytic activation after pulmonary trauma is not prevented by high dose steroids.

Local trauma to the lungs induces a temporary permeability disturbance with reduction in the osmotic reflection coefficient of a sheep lung lymph model. Proteolytic enzymes may be involved in this microvascular injury. In the present study, we tested the hypothesis that pretreatment with methylprednisolone prevents activation of proteolytic systems after pulmonary trauma and that these systems are of etiological importance in the development of the pulmonary lesion. Central markers of proteolytic cascade systems were monitored in sheep subjected to local trauma to the lungs (lung lymph fistula preparation) with (n = 7) or without (n = 7) methylprednisolone (30 mg/kg) pretreatment. In control animals, reduced levels of prothrombin, antithrombin, kallikrein inhibitors, antiplasmin, and increased level of plasminogen activator inhibitor (PAI) indicated systemic activation of the coagulation, kallikrein-kinin, and fibrinolytic systems. These changes, except for PAI, were more pronounced in lung lymph. High levels of thromboxane A2 and 6-keto prostaglandin F1 alpha were found in lymph. In steroid-pretreated animals, the prostanoid response was attenuated, but all other variables were similar to control animals; thus, steroids did not prevent either local or systemic proteolytic enzyme activation caused by local trauma to the lung. The etiological role of this activation in the development of lung lesion has not yet been evaluated.

Animals↗

The enhanced responsiveness of hypophyseal DA receptors in female rats induced by repeated reserpine treatment is not due to decreased oestrogen secretion.

In a previous study we have demonstrated that repeated reserpine treatment markedly enhances the intrinsic activity of the partial dopamine (DA) agonist (-)-3-PPP (preclamol) on pituitary DA receptors in female rats. This effect was attributed to the DA-depleting action of reserpine. However, since reserpine may also decrease oestrogen secretion, and since this hormone is known to affect dopaminergic transmission, experiments with ovariectomized, oestrogen-replaced female rats were undertaken. Ovariectomized rats were administered a depot preparation of oestradiol valerate in a dose that, according to literature data, yields physiological or slightly supraphysiological plasma concentrations of oestrogen. In spite of this treatment, repeated reserpine administration was found to substantially increase the intrinsic activity of (-)-3-PPP, as well as that of the partial DA agonist TDHL (terguride), on female pituitary DA receptors. It was concluded that repeated reserpine treatment increases pituitary DA receptor responsiveness in female rats by depleting DA, rather than by decreasing oestrogen secretion.

Animals↗

Skin flap circulation. Simultaneous monitoring with laser Doppler and electromagnetic flowmeters in the pig island buttock flap.

Twenty-two island skin flaps based on the deep circumflex iliac vessels were elevated in pigs. A comparative study of Laser Doppler flowmetry (LDF) and electromagnetic flowmetry (EMF) was undertaken. Flow values were compared during selective arterial and venous occlusion, nerve stimulation and intra-arterial noradrenaline or papaverine injection. The effectiveness of flap temperatures and blood gas data in monitoring vascular occlusions was also investigated. Similar and simultaneous responses in LDF and EMF values were noted during the different experimental manipulations, but for single simultaneous LDF/EMF observations from different animals the correlation coefficients were poor. The accuracy of EMF measurements in monitoring total flap inflow was confirmed by a high correlation with total venous outflow values. Major vascular occlusions also resulted in significant changes in the flap temperatures, and in the flap blood gases.

Animals↗

Thrombosis after hip replacement. Relationship to the fibrinolytic system.

Twenty-nine patients were operated on with the Charnley hip prosthesis. All the patients were given dextran 70 as thrombosis prophylaxis. Deep vein thrombosis (DVT) was diagnosed in 10 patients with the radioactive fibrinogen uptake test and phlebography. Variables of coagulation and fibrinolysis were studied before and after surgery. Tissue plasminogen activator (t-PA) activity in the plasma without venous occlusion decreased postoperatively, but there was no correlation with DVT. The t-PA activity in venous occlusion plasma was not reduced after surgery. Plasminogen activator inhibitor (PAI-1) levels were raised immediately postoperatively. There was a significant correlation between preoperative PAI-1 activity and development of postoperative DVT (P less than 0.05). Patients developing DVT had higher levels of PAI-1 postoperatively than patients not developing DVT. A defective fibrinolytic system, as defined by high PAI-1 activity, thus predisposed to postoperative DVT.

Aged↗

Idiopathic facial palsy in pregnancy and the puerperium.

An association between pregnancy and idiopathic facial palsy has been observed previously. A five year review of patients admitted to the Brigham and Women's Hospital disclosed 18 new instances of pregnancy associated Bell's palsy. Twelve patients became symptomatic during the third trimester and six during the first two weeks post partum. Primiparity was not a risk factor for pregnancy-associated facial palsy, but pre-eclampsia was six times more prevalent among patients in this study than among the general population of gravid women. Of 14 patients observed, eight had complete return of mimetic function within three months of the onset of symptoms. The remaining six patients had only mild residual facial weakness after a mean interval of 22 months. The administration of steroids did not appear to influence recovery.

Adolescent↗

Heparin and fibrinolysis--comparison of subcutaneous administration of unfractionated and low molecular weight heparin.

The effects on the fibrinolytic system after a single s.c. bolus injection (at 9 a.m.) of either 5000 IU conventional heparin or 5000 anti-Xa U of a fractionated low molecular weight heparin (Fragmin, KabiVitrum, Sweden) were investigated in 9 healthy volunteers. The effects were compared to those of an injection of normal saline in 6 volunteers. Samples for biochemical analyses were taken regularily during 6 hours after drug or placebo administration. In the coagulation system the following parameters were measured: Activated partial thromboplastin time (APTT), anti-Xa activity, thrombin time and fibrinogen. The fibrinolytic system was monitored by analysing: plasminogen, alpha 2-antiplasmin, fibrin(ogen) degradation products (FDP), euglobulin clot lysis time (ECLT), tissue plasminogen activator (t-PA) activity, t-PA antigen and plasminogen activator inhibitor (PAI) activity. Injection of the 2 drugs was followed by elevations in APTT and anti-Xa activity, and were more pronounced for Fragmin than heparin. The fibrinolytic system exhibited a diurnal variation with decreasing PAI activity and increasing t-PA activity during the day. Volunteers receiving normal saline (placebo) showed a similar pattern. The results were unrelated to heparin. It is concluded from this study that neither heparin nor Fragmin had any significant effect on the fibrinolytic parameters when measured after a single s.c. bolus injection since the observed variations were within the diurnal range.

Adult↗

Determination of plasminogen activator inhibitor in plasma using t-PA and a chromogenic single-point poly-D-lysine stimulated assay.

A two stage method for determination of plasminogen activator inhibitor (PAI) activity in blood plasma is described. In the first stage, an excess of single-chain tissue plasminogen activator (t-PA) is added to plasma. In the second stage, the residual t-PA activity is determined with a plasminogen/chromogenic plasmin substrate assay utilizing poly-D-lysine as a t-PA stimulator. The method proved accurate since it correctly determined the PAI activity (range 0 to 110U/mL) in citrated plasma samples with levels established by time course analysis of t-PA inhibition and by titration with t-PA. Furthermore, correlation was excellent (r = 0.97) with the method of Chmielewska et al Thromb. Res. 31, 427-436, 1983. Plasma samples with increased platelet factor 4, indicative of platelet release, did not show increased levels of PAI activity.

Blood Platelets↗

Effects of sex steroids on growth hormone responses to clonidine and GHRH in reserpine pretreated rats.

Administration of reserpine in a dose causing depletion of brain monoamines led to a complete suppression of the pulsatile secretory pattern of growth hormone (GH) in gonadectomized (GX) as well as in sham-operated male and female rats. In GX animals of both sexes treated with estradiol, but not in those treated with testosterone or dihydrotestosterone (DHT), the reserpine induced inhibition of GH release was partially antagonized. Administration of the alpha 2-adrenoceptor agonist clonidine caused secretion of GH in reserpine pretreated, sham-operated rats. In GX male rats GH responses to clonidine were blunted, while in GX males treated with testosterone or estradiol, but not in those treated with DHT, the responses were restored. In female rats gonadectomy did not significantly affect the GH releasing effect of clonidine. However, administration of estradiol to GX females led to enhanced responses to the alpha 2-agonist. Administration of the GH releasing hormone (GHRH) induced pronounced GH secretion in reserpine pretreated animals of both sexes; this effect was not significantly affected by gonadectomy. In GX males, however, GH responses to GHRH were enhanced by replacement with estradiol or testosterone, while in GX females, estradiol, but not testosterone, had the same effect.

Animals↗

The intrinsic activity of (-)-3-PPP (preclamol) on pituitary DA receptors in female rats is enhanced following chronic DA depletion.

The present investigation was aimed at comparing the influence of the partial dopamine (DA) receptor agonist (-)-3-PPP (preclamol) on prolactin release in acutely hyperprolactinemic but otherwise intact female rats and female rats subjected to chronic DA depletion. One group of animals received daily vehicle injections (controls) and another group daily reserpine (1 mg/kg) injections for a period of seven days. On the eighth day all animals were administered 10 mg/kg of reserpine in order to eliminate endogenous DA and elevate serum prolactin levels. In the control group (-)-3-PPP lowered serum prolactin levels only moderately. In contrast, in the chronically reserpinized female rats, a pronounced reduction of prolactin secretion was observed. It is suggested that this increase in intrinsic activity of (-)-3-PPP following chronic DA depletion reflects an enhanced responsiveness of hypophyseal DA receptors, possibly due to conformational changes in the receptor molecules. Our observations lend further support to the hypothesis that an inverse relationship exists between the intrinsic activity of a mixed agonist/antagonist and the degree of previous receptor occupancy.

Animals↗

Growth hormone responses to the alpha 2-adrenoceptor agonist guanfacine and to growth hormone releasing hormone in depressed patients and controls.

Growth hormone (GH) responses to the alpha 2-adrenoceptor agonist guanfacine and to GH releasing hormone (GHRH) were measured in 13 patients fulfilling Research Diagnostic Criteria and DSM-III criteria for major depressive disorder and in 13 controls matched for age and sex. Dexamethasone suppression tests were performed in all subjects. The peak GH response to guanfacine correlated to the peak GH response to GHRH both in depressed patients and in controls. Neither the response to guanfacine nor the response to GHRH was significantly lower in depressed patients than in controls. Dexamethasone suppression tests, which were performed about 3 days before the GH stimulation tests, were abnormal in 61% (8/13) of the depressed patients but in none of the controls. No difference between dexamethasone suppressors and nonsuppressors with respect to GH response to guanfacine or GHRH was observed. The data are discussed in relation to the blunted GH response to clonidine described in depression.

Adrenergic alpha-Agonists↗

Increase in myoglobin content and decrease in oxidative enzyme activities by leg muscle immobilization in man.

Biopsies from m. quadriceps femoris from the operated leg of nine patients were taken before, and 6 weeks after, knee surgery. During the whole postoperative period the operated leg was immobilized with the knee in 40-50 degrees of flexion. Myoglobin (MYO) and the enzymes citrate synthase (CS), creatine kinase (CK) and its isozymes MB (CK-MB) and mitochondrial CK (CK-MIT), aspartate aminotransferase (ASAT), phosphofructokinase (PFK) and lactate dehydrogenase (LD) were determined on the biopsies. Citrate synthase, ASAT, CK, CK-MB, CK-MIT and LD activities were decreased (12-30%) after the postoperative leg immobilization period. Phosphofructokinase did not change, while MYO content was increased (16%). In conclusion, a different control of the synthesis of oxidative enzymes and MYO is suggested, as the induced changes following immobilization were in opposite directions. The function of the increased MYO content may be to facilitate the oxygen extraction.

Adolescent↗

Method for skin blood flow studies in the pig.

In this methodological paper a quantitative blood flow measuring technique in porcine skin is described. The anatomy, technical preparation and surgical technique is emphasized. Baseline recordings yielded a total blood flow of 6.6 +/- 0.9 (S.E.) cc/100 g/min and an oxygen consumption of 0.16 +/- 0.02 cc/100 g/min at a dermal temperature of 35 degrees C. Approximately 75% of the experiments were successful and unsuccessful experiments were mainly due to malignant hyperthermia in the pig or inability to cannulate the vessels.

Animals↗

Experimental pretransfer expansion of free-flap donor sites: II. Physiology, histology, and clinical correlation.

There is a statistically significant increase in blood flow into expanded cutaneous and myocutaneous flaps in a pig model over controls. The vascular trees within flaps enlarge following expansion, and pronounced neovascularization is seen in the papillary dermis and capsular layers. Experimentally, there is differential thinning of all tissue layers except the epidermis. A successful clinical application of this technique, by free-tissue transfer of an expanded fasciocutaneous scapular flap, is described. The technique is applicable when altered flap size or contour is desired.

Adipose Tissue↗