[Biological aspects of sexual orientation: similar behavior in mice and men].
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Animals↗
Biomedical subjects
K Larsson
Publications and source records attributed to K Larsson.
Ultrastructural changes in spinal nerve roots induced by autologous nucleus pulposus.
STUDY DESIGN: Ultrastructural changes were analyzed by transmission electron microscopy in nerve roots exposed to autologous nucleus pulposus experimentally. OBJECTIVES: To assess if ultrastructural changes were present in areas with no light microscopic changes in nerve roots exposed to autologous nucleus pulposus in a pig model. SUMMARY OF BACKGROUND DATA: Previous analyses have shown that there is focal nerve fiber damage in nerve roots exposed to autologous nucleus pulposus in the pig. These changes could not fully explain the reduction in nerve conduction velocity seen in the same nerve roots. In the present study, the parts of the nerve roots that did not display breakdown of axons or myelin sheaths at the light microscopic level were analyzed regarding ultrastructural changes. METHODS: In a previous study, nucleus pulposus was harvested from a lumbar disc and placed epidurally onto the cauda equina at the sacrococcygeal level in pigs. Retroperitoneal fat was used as control. After 1, 3, and 7 days, the nerve roots were excised and processed for light microscopy. Parts of the nerve roots that appeared normal at the light microscopic level were further processed for the present electron microscopic examination. RESULTS: Significant ultrastructural changes, such as expansion of the Schwann cell cytoplasm and intracellular edema with vesicular swelling of the Schmidt-Lanterman incisures, were observed in nerve fibers with normal axons. Although present after nucleus pulposus and control application, the changes were more pronounced after the application of nucleus pulposus. CONCLUSIONS: Epidural application of autologous nucleus pulposus without any pressure may induce not only nerve function impairment but also axonal injury and significant primary Schwann cell damage with vesicular swelling of Schmidt-Lanterman incisures. However, because axonal and Schwann cell changes affected only part of the nerve fibers, further causes of the impaired nerve conduction need to be determined.
Animals↗
Time course of interleukin-6 and tumor necrosis factor-alpha increase in serum following inhalation of swine dust.
Inhalation of swine dust induces airway inflammation and general symptoms, such as fever and malaise. In the present investigation, the presence and time course of changes in tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in serum were studied to evaluate possible mechanisms by which inhalation of swine dust induces general symptoms. A group of 14 previously nonexposed subjects weighed swine for 3 h. The average +/- SD inhalable dust concentration was 22.4 +/- 4.7 mg/m3 and endotoxin, 1.2 +/- 0.4 microgram/m3. TNF-alpha in serum increased from 2.5 (1.8 to 3.1) ng/L (median, interquartile range) before exposure to maximum values 10.0 (4.6 to 15.7) ng/L between 3 and 5 h after the start of exposure. IL-6 increased from less than 1.5 to 21.4 (18.6 to 33.6) ng/L 4 to 11 h after the start of exposure. Maximum IL-6 occurred 1 to 5 h after the maximum TNF-alpha. In many subjects, however, an early rise in IL-6 parallel to the change in TNF-alpha was seen. The results that some of the peripheral reactions to swine dust might be mediated by TNF-alpha and IL-6. The early rise in IL-6 implies multiple origins of the IL-6.
Adult↗
Beta 2-agonist treatment reduces beta 2-sensitivity in alveolar macrophages despite corticosteroid treatment.
Alveolar macrophage beta 2-adrenoceptor sensitivity and bronchodilator responses to inhaled terbutaline were investigated before and after 2 wk of oral treatment with terbutaline 7.5 mg twice a day in healthy volunteers. The influence of corticosteroid treatment was examined by giving 10 subjects budesonide 400 micrograms twice a day by inhalation throughout the treatment period, and by giving 10 subjects 40 mg prednisolone and 10 subjects placebo orally 12 h before the second examination. Terbutaline treatment elicited marked attenuation (approximately 75% reductions) of isoprenaline-induced cyclic AMP accumulation in the alveolar macrophages. Responses to prostaglandin E1 were not influenced by treatment, suggesting homologous beta-adrenoceptor desensitization. Corticosteroid administration failed to either prevent (budesonide) or reverse (prednisolone) this desensitization. Bronchodilator responses to terbutaline were not altered by treatment in either group. We conclude that the beta 2-adrenoceptor sensitivity of human alveolar macrophages is markedly and selectively depressed by beta 2-agonist treatment and that corticosteroid treatment, contrary to previous hypotheses, fails to influence this phenomenon. Studies on the mechanisms involved are needed. The importance of alveolar macrophages in asthma is unclear, but the present data in humans are of interest in relation to possible effects of continuous beta 2-agonist treatment on inflammatory mechanisms in the airways.
Administration, Inhalation↗
In vivo effects of 13-cis retinoic acid treatment on the concentration of proteins and lipids in serum.
A number of serum components, whose concentrations or gene expression have been shown to be modulated by all-trans retinoic acid in vitro, were monitored in patients before and during treatment with Roaccutane (13-cis retinoic acid, 40-60 mg/day) for severe acne. The 13-cis retinoic acid concentration in serum rose from 5.25 +/- 1.09 to 593 +/- 65 nmol/l (mean +/- SD) 24 h after the latest dose. The concentration of all-trans retinoic acid in serum under Roaccutane treatment was measured in model experiments and shown to be 10-20 nmol/l i.e., 2-4 times the basal levels (4.65 +/- 0.85 nmol/l) when the 13-cis retinoic acid concentration was 370-980 nmol/l. The concentrations of creatine kinase-MB, apolipoprotein B, total cholesterol and LDL cholesterol increased significantly while the other measured serum components, including lipoprotein lipase activity, were unaffected by Roaccutane treatment.
Acne Vulgaris↗
Novel forms of B-domain-deleted recombinant factor VIII molecules. Construction and biochemical characterization.
Recombinant molecules similar to the smallest active plasma-derived factor VIII molecule, a complex of an 80-kDa and a 90-kDa polypeptide chain lacking the B domain, have been produced using various factor VIII cDNA constructs in order to obtain primary translation products which were efficiently processed into the 80 + 90-kDa complex. Three types of single-chain cDNAs encoding B-domain-deleted derivatives factor VIII were designed, taking account of sites at Arg740 and Glu1649, assumed to be important for processing factor VIII. In the type 1 constructs, either Arg747, Arg752, or Arg776 in the N-terminal region of factor VIII B domain was fused to the N-terminus (Glu1649) of the 80-kDa subunit. In the type 2 construct r-VIII SQ, Ser743 was fused to Gln1638, creating a link of 14 amino acids between the C-terminus (Arg740) of the 90-kDa chain and N-terminus of the 80-kDa chain, whereas in type 2 r-VIII RH, Arg747 was fused to His1646. In the type 3 constructs, the B-domain was completely removed or replaced with 1-4 Arg residues. After expression in Chinese hamster ovary cells, the type 1 derivatives and the type 3 derivatives with 0-2 Arg residues inserted were found to be only partially processed and contained a large amount of the 170-kDa primary translation product. In contrast, most of the type 2 derivatives r-VIII SQ and r-VIII RH and the type 3 derivatives r-VIII R4 and r-VIII R5 containing three or four extra Arg residues preceding the N-terminus of the 80-kDa chain were processed into the desired 80 + 90-kDa chain complexes. The feature common to the most efficiently processed factor VIII deletion derivatives was that they contained the recognition motif for proteolytic cleavage by the membrane-bound subtilisin-like protease furin, which is expressed in most types of cells; that is, basic amino acid residues at positions -1 and -4 relative to the cleavage site at Glu1649. Biochemical studies of r-VIII SQ and r-VIII R5, two of the most effectively processed factor VIII derivatives, showed that both proteins had a normal factor VIII cofactor function, and had N- and C-termini of the 80-kDa and 90-kDa chains corresponding to those found in plasma-derived factor VIII.
Amino Acid Sequence↗
A rapid transport route between the epidural space and the intraneural capillaries of the nerve roots.
STUDY DESIGN: The possibility of epidurally applied substances reaching the intraneural capillaries of the spinal nerve roots and cauda equina was assessed in the pig sacrococcygeal spine. METHODS: The presence of Evans blue-labelled albumin in intraneural capillaries after epidural application for 1, 10, or 30 minutes was studied with fluorescence microscopy. Ink angiography was used to determine whether there were any direct communicating vessels between the epidural vein plexus and the intraneural capillaries. RESULTS: Evans blue-labelled albumin was present in the intraneural capillaries 1 minute after epidural application. Microangiography demonstrated small venules that connected the epidural vein plexus and the intraneural capillaries. CONCLUSIONS: The results of this study demonstrated a rapid transport route between the epidural space and the intraneural capillaries. The results suggest that nucleus pulposus material, as well as epidurally applied substances, such as local anesthetic drugs or epidurally injected corticosteroids, may have a rapid, direct transport route to the axons of the spinal nerve roots. The demonstrated transport route also may be related to the mechanisms behind epidural anesthesia and spinal nerve root infiltration.
Albumins↗
Sexual preference and feminine and masculine sexual behavior of male rats prenatally exposed to antiandrogen or antiestrogen.
Male rats were prenatally (Day 10-19 of pregnancy) exposed to an antiestrogen, nitromifene citrate (CI628, 1 mg/rat), or an antiandrogen, cyproterone acetate (CA, 10 mg/rat), and in adulthood were examined for their exhibition of male-typical and female-typical behavior pattern. Treatment with CI628 abolished the capacity of the adult intact male to ejaculate, enhanced his potential to exhibit feminine sexual behavior, and decreased the intensity of the level of female-oriented behavior in a two-choice stimulus situation (estrous female vs active male). The administration of testosterone (T) did not alter these behaviors. Males exposed to CA showed low levels of lordosis behavior and normal levels of female-oriented preference. Further, they showed increased frequency of mounts and decreased number of intromissions, and only a few males ever ejaculated. Macroscopic inspection of the genital organs of the CI628-treated males revealed complete absence of the prostate. The dissections of the CA-treated males revealed a poorly developed penis and a blind-ending vagina. It was concluded that prenatal estrogen (E) is involved (1) in determining the development of mechanisms destined to mediate the display of male-typical behaviors in adulthood, (2) in suppressing the development of mechanisms of female-typical behaviors, and (3) seems to stimulate neural mechanisms influencing sexual preference behavior in the adult.
Androgen Antagonists↗
Clozapine acts as a 5-HT2 antagonist by attenuating DOI-induced inhibition of male rat sexual behaviour.
Evidence has been reported that clozapine may derive part of its therapeutic effects in treatment-resistant schizophrenic patients by interacting with the serotonin system. Among the few behavioural models available to test the hypothesis of an interaction of clozapine with 5-HT2 receptors, male rat sexual behaviour is particularly useful, since in this behaviour 5-HT1A and 5-HT2 receptors have opposite functions. Stimulation of 5-HT1A receptors facilitates ejaculatory behaviour and stimulation of 5-HT2 receptors inhibit ejaculation. In the present study, male rat sexual behaviour was depressed by treatment with DOI (1.0 mg/kg), a selective 5-HT2 receptor agonist. The depressive effect of DOI was attenuated by the administration of clozapine (0.1-1.0 mg/kg) in doses that by themselves did not significantly affect sexual behaviour. It was concluded that clozapine in the male rat sexual behaviour model may be interpreted as serving as a 5-HT2 antagonist.
Animals↗
Low serum concentration of all-trans and 13-cis retinoic acids in patients treated with phenytoin, carbamazepine and valproate. Possible relation to teratogenicity.
All-trans retinoic acid deficiency resulting from ethanol's interference with the synthesis of all-trans retinoic acid from retinol was recently suggested to cause the malformations of the fetal alcohol syndrome. Phenytoin, carbamazepine and valproate, might be teratogenic because they lower the concentration of all-trans retinoic acid in serum, by inducing the enzyme systems in the liver responsible for the metabolism of the all-trans retinoic acid, or by other mechanisms. Here we show, that in patients given therapeutic doses of phenytoin, carbamazepine and valproate, serum all-trans and 13-cis retinoic acid concentrations are indeed significantly lowered. We propose that drugs with this ability should be considered as potential teratogens.
Adult↗
Adrenalectomy does not prevent the ability of 8-OH-DPAT to decrease the ejaculatory threshold in male rats.
The present experiments demonstrate that 8-OH-DPAT (0.25 mg/kg SC, - 15 min) produced a decrease in the ejaculatory threshold to the same extent in adrenalectomized male rats as in sham operated controls. Both groups of animals displayed a marked and statistically significant decrease in number of mounts and penile intromissions preceding ejaculation and in the ejaculation latency, as a result of treatment with 8-OH-DPAT. Adrenalectomy per se did not affect any aspect of the male rat's sexual behavior (latency to first intromission, number of mounts or penile intromissions, ejaculation latency or the postejaculatory interval). The surgical removal of the adrenals was verified by measurements of plasma corticosterone levels. It is concluded that well documented effects of 8-OH-DPAT on adrenal secretions do not contribute to its ability to decrease the ejaculatory threshold in male rats.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Sympathoadrenal responses to bronchoconstriction in asthma: an invasive and kinetic study of plasma catecholamines.
1. Bronchoconstriction does not seem to be a stimulus for sympathoadrenal activation, as judged by venous plasma concentrations of noradrenaline, adrenaline or neuropeptide Y-like immunoreactivity. However, venous measurements have methodological drawbacks. In the present study arterial and mixed venous (pulmonary arterial) levels of these variables were determined before and after histamine-induced bronchoconstriction in non-medicated asthmatic subjects. In addition, noradrenaline kinetics in plasma (isotope dilution) and the pulmonary overflows of noradrenaline and neuropeptide Y-like immunoreactivity were determined. 2. Histamine inhalation induced bronchoconstriction; forced expiratory volume in ls decreased by 38.7% +/- 4.1% (SE) and arterial PO2 by 3.0 +/- 0.9 kPa. This acute bronchoconstriction induced significant elevations of arterial and mixed venous plasma noradrenaline from < or = 1.18 nmol/l to > or = 1.40 nmol/l. The clearance of NA from plasma increased marginally. Thus, the arterial plasma NA response was due to increased spillover of noradrenaline to plasma (from 1.80 +/- 0.18 to 2.52 +/- 0.36 mmol min-1/m2 at maximal bronchoconstriction, with a subsequent further increase). There were no elevations of adrenaline or neuropeptide Y-like immunoreactivity in arterial plasma. 3. No sympathetic activation could be demonstrated in the lungs (pulmonary noradrenaline or neuropeptide Y-like immunoreactivity overflow), and no alterations in pulmonary vascular resistance or cardiac output were observed. Neither arterial nor mixed venous plasma concentrations of adrenaline were influenced by bronchoconstriction. 4. Acute bronchoconstriction thus leads to peripheral sympathetic activation (possibly due to the increased work of breathing) which does not involve the lungs.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Comparison of the effect of the linseed extract Salinum and a methyl cellulose preparation on the symptoms of dry mouth.
The effect of a linseed extract Salinum and a sodium carboxymethyl cellulose preparation called MAS-84 was compared with regard to its effect on the symptoms of dry mouth. Twenty patients with xerostomia, who had been treated for cancer in the head and neck by radiation were recruited from the clinic for maxillofacial surgery, Malmo University Hospital. Following radiation treatment the salivation was severely reduced. The symptoms of a general feeling of a dry mouth, difficulties in chewing and swallowing, taste disturbances, problems with speech and mouth burning were registered on a subjective verbal rating scale. In addition plaque index and gingival bleeding were determined. The study design was crossover and performed single blind. The experimental period was 7 weeks. The patients were randomly divided into 2 groups. One group used Salinum and the other MAS-84 for 3 weeks. The fourth week was a wash out period and for the next three weeks the patients shifted preparation. Each of the preparations was used ad libitum. Registrations of the various parameters were undertaken on days 0, 7 and 21 of the respective period. At the initial examination all patients reported considerable disturbances from mouth-dryness. These symptoms were reduced in 15 patients during the Salinum period and in 9 during the MAS-84 period. The relief was significantly more pronounced during the use of Salinum compared to that during the use of the methyl cellulose preparation. On day 21 plaque and gingival bleeding were significantly reduced during the Salinum period but not during the MAS-84 period. The results of the present study confirm those of a previous pilot study and indicate that the linseed mucilage significantly reduced the symptoms of dry mouth. This effect increased with increasing time of saliva substitute use. The linseed mucilage Salinum appeared to be a suitable saliva replacement in mouth dry patients.
Aged↗
Exogenous phospholipid reduces postoperative peritoneal adhesions in rats.
OBJECTIVE: To find out if the previously described ability of phosphatidylcholine to reduce peritoneal adhesions is specific to it, or if other phospholipids such as phosphatidylinositol (PI) or DL-phosphatidylcholine dilauryl (DL-PC) have similar effects. DESIGN: Laboratory experiment. SETTING: University hospital, Sweden. MATERIALS: 160 rats which had had intraperitoneal adhesions induced at laparotomy by peritoneal defects repaired in one of two models. INTERVENTIONS: PI was given intraperitoneally either once in a dose of 20 or 40 mg/rat at the end of the operation, or at the end of the operation and repeated on the second and third postoperative days. DL-PC was given once at the end of the operation in a dose of either 20 or 40 mg/rat. MAIN OUTCOME MEASURES: Adhesions were assessed a week after operation by an observer who was unaware of the treatment given. RESULTS: PI given on three consecutive days significantly reduced adhesions formed postoperatively in both models (p < 0.05). Neither PI nor DL-PC given in a single dose of 20 mg/rat had any effect, whereas both PI and DL-PC given in single doses of 40 mg/rat significantly reduced adhesions (p < 0.05). CONCLUSION: Both PI and DL-PC are effective in the prevention and limiting of postoperative adhesions in rats.
Animals↗
Allergic sensitization is associated with increased bronchial responsiveness: a prospective study of allergy to laboratory animals.
The purpose of this prospective study was to investigate the extent of change in bronchial responsiveness and the prognostic value of methacholine provocation in early sensitization to laboratory animals. Thirty eight laboratory technicians were studied during training (before first exposure) and after having been exposed to laboratory animals for a median 18 (range 5-33) months. On both occasions they were subjected to spirometry, bronchial methacholine challenge, skin-prick tests and blood sampling, and responded to questionnaires. Nine (24%) developed laboratory animal allergy (LAA), defined as animal work-related symptoms (n = 8), or specific immunoglobulin E (IgE) (n = 7) or both. In the LAA group, bronchial responsiveness was normal before employment, but had increased significantly at follow-up compared to technicians who had not developed LAA. Six of the nine LAA subjects had a more than threefold increase in bronchial responsiveness, and three of these reported chest symptoms. Spirometric values were not different between the groups prior to exposure or at follow-up, and had no prognostic value. However, a pre-employment level of total IgE > 100 kU.L-1 predicted the development of LAA (relative risk 2.8). Thus, early LAA was associated with increased bronchial responsiveness in most subjects. In contrast to total IgE, the level of pre-employment bronchial responsiveness or lung function did not influence the magnitude of change in responsiveness, nor predict sensitization.
Adolescent↗
[Physiological processes control parental behavior. Hormonal ties between mother and child].
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Estrogens↗
Effects of FG 5893, a new compound with 5-HT1A receptor agonistic and 5-HT2 receptor antagonistic properties, on male rat sexual behavior.
In the present study male rat sexual behavior was used to explore the functional properties of FG 5893, a newly developed diphenylbutylpiperazinepyridyl derivative which is a 5-HT1A receptor agonist and a 5-HT2 receptor antagonist. Treatment with FG 5893 (0.1-6.0 mg kg-1) stimulated male rat sexual behavior, as evidenced by a decrease in the number of mounts and intromissions to elicit ejaculation, and a shortening of the ejaculation latency. The stimulatory effects varied in a dose-dependent manner, reaching a maximum at 3.0 mg kg-1. Pretreatment with (+/-)-pindolol (0.5 mg kg-1 -30 min), a selective 5-HT1A receptor antagonist, completely antagonized the stimulatory effects of FG 5893 (1 mg kg-1 -20 min) on male sexual behavior. In addition, the behavioral action of FG 5893 was investigated on various components of the 'serotonin behavior syndrome' including flat body posture, forepaw treading, and lower lip retraction. The effects obtained were compared with those induced by treatment with 8-hydroxy-2(di-n-propyl-amino)tetralin (8-OH-DPAT), the prototype of a 5-HT1A receptor agonist. Compared to 8-OH-DPAT, a 100 times higher dose of FG 5893 (10 mg kg-1) was needed to elicit flat body posture while forepaw treading was never seen. Lower lip retraction was elicited by the lowest doses of FG 5893 (0.1 mg kg-1) and 8-OH-DPAT (0.03 mg kg-1). Treatment with (+/-)-pindolol reduced flat body posture elicited by 8-OH-DPAT and completely eradicated the flat body posture induced by FG 5893.(ABSTRACT TRUNCATED AT 250 WORDS)
8-Hydroxy-2-(di-n-propylamino)tetralin↗
[Better results in sports after use of anti-asthmatic drugs?].
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Adrenal Cortex Hormones↗