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Biomedical subjects

K Larsson

Publications and source records attributed to K Larsson.

At least 127 records · Page 7Linked to original sources

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↗

The influence of body composition on left ventricular mass and other echocardiographic and Doppler measurements in 70-year-old males.

Heart morphology and function are often related to body size. The most common way to standardize for body composition is to divide these measures by body surface area (BSA). It has, however, been suggested that left ventricular mass (LV mass) ought to be indexed for height and that cardiac output is influenced by the body fat distribution. As part of a health screening programme of 70-year-old males in Uppsala, Sweden, 100 consecutive men were investigated with echocardiography and Doppler with regard to cardiac morphology and function. These measures were related to an evaluation of body composition using an X-ray method (dual energy X-ray absorptiometry). Lean body mass was strongly related to BSA and body weight (r = 0.90 and 0.89, respectively; P < 0.0001), and to a lesser degree to height (r = 0.70, P < 0.0001). In the healthy part of the population (n = 39), relationships between LV mass on the one hand and lean body mass, BSA and height on the other were seen (r = 0.51, 0.51 and 0.50, respectively; P < 0.01). Stroke volume calculated according to Teichholtz (but not when calculated with Doppler) showed a significant correlation to lean body mass (r = 0.38, P < 0.05). Also, left ventricular diameter and the thickness of the free wall were related to lean body mass (r = 0.40 and 0.39, respectively; P < 0.05). All of the evaluated relationships were generally weaker and in most cases no longer significant when evaluated in part of the population with diseases known to affect the heart. No significant correlations were seen between the size of the left atrium, septal thickness or indices of diastolic function (E/A-ratio, isovolumic relaxation time, deceleration time) and the indices of body composition. No measures of cardiac morphology and function were significantly related to the amount of body fat or body bone. LV mass, stroke volume and left ventricular diameter were found to be correlated with lean body mass, but not with the amount of fat, in healthy 70-year-old males. Theoretically, it is optimal to adjust for lean body mass, but in clinical practice, BSA is to be preferred.

Aged↗

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↗

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↗

Asthma, lung function, and bronchial responsiveness in welders.

The incidence of asthma was compared in welders welding in stainless steel (SS) or mild steel (MS). The study was comprised of welders who had been welding for at least 6 months during the preceding 10 year period in four companies, but who had not been welding occupationally prior to this time. The inclusion criteria were met by 42 SS welders with a total welding time of 196 years. Sixteen of these had left work, six because of airway symptoms. Eighty-five MS welders with a total welding time of 403 years were included. Forty-eight of these had left work, 10 citing airway symptoms as a main reason for leaving work, according to responses in a mailed questionnaire. Ex-welders with airway symptoms were in some cases further investigated with spirometry and bronchial provocation tests. In other cases, medical records gave a clear diagnosis. In addition, bronchial responsiveness and lung function were measured and airway symptoms were recorded in presently active welders. Twenty-three of the 26 active SS steel welders and 23 of the 37 active MS steel welders were examined, together with a reference group of 26 (out of 30 invited) vehicle assemblers. There was no difference in the incidence of welding-associated asthma (5% for SS, 7% for MS welders per 1,000 welding-years). Bronchial responsiveness and lung function in active welders was normal and did not differ between MS and SS welders or between welders and a reference group of vehicle fitters. Welders had a significantly higher prevalence of airway symptoms as compared to vehicle fitters.

Adult↗

Effects of infusion of parathyroid hormone and primary hyperparathyroidism on formation and breakdown of type I collagen.

The influence of chronic and acute exposure to parathyroid hormone (PTH) on formation and breakdown of type I collagen, using two recently developed radioimmunoassays for serum PICP (the carboxyterminal propeptide of type I procollagen) and serum ICTP (the carboxyterminal telopeptide of type I collagen), have been evaluated. Fasting morning values were obtained from 18 women with primary hyperparathyroidism (HPT) and an equal number of age-matched, healthy controls. A 24-hour infusion of synthetic human parathyroid hormone (PTH 1-38) was performed in 14 healthy females. The patients with HPT had higher values for serum ICTP than the controls (6.0 +/- 3.0 and 4.1 +/- 2.1 micrograms/liter; P < 0.05), whereas the serum PICP concentrations were not different (170 +/- 72 and 151 +/- 65 micrograms/liter; n.s.). During infusion of PTH in healthy subjects, there was an increase of the serum ICTP concentrations (from 3.6 +/- 1.3 to 4.4 +/- 1.8 micrograms/liter; P < 0.001) whereas those of serum PICP decreased (from 185 +/- 78 to 118 +/- 42 micrograms/liter; P < or = 0.0001). The increase of serum ICTP during infusion of PTH was positively related to the increase of serum calcium and other indices of bone resorption, i.e., fasting urinary excretions of hydroxyproline and calcium. The decrease of serum PICP was also related to the changes of serum ICTP and hydroxyproline in urine, serum calcium, and alkaline phosphatase but not to osteocalcin, an established marker of osteoblastic activity. The findings support the fact that serum ICTP is a valuable method for evaluating bone resorption and is also easy to perform.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Age-dependent variations in the sexual preference of male rats.

Male rats were tested for their sexual preference behavior at either 37, 70, 90, or 150 days of age on three different occasions; while still sexually naive, after sexual experience with a receptive female, and while sexually aroused by having initiated copulation. These tests resulted in the following findings: a) 37-day-old sexually naive males showed a preference for other males and failed to show a preference for either sex after exposure to females; b) 70- and 90-day-old males showed a statistically significant preference for the female after acquiring sexual experience; c) 150-day-old animals showed a female-oriented preference only after being sexually aroused with two intromissions preceding the preference test, and d) none of the age groups tested showed a female-oriented preference without previous exposure to females. It was then concluded that a) female-oriented behavior requires sexual experience and b) the effects of experience varies with age.

Aging↗

Experience modulates the influence of gonadal hormones on sexual orientation of male rats.

The aim of this study was to investigate whether heterosexual experience influences the male's partner preference and the role of gonadal hormones, including several androgens and estradiol, on female-oriented behavior. In the first experiment, the animals were exposed to a four-stimuli test situation including a sexually active male, a castrated male, an estrous female, and an ovariectomized (ovx) female. Castrated naive and experienced male rats were implanted with either testosterone (T), estradiol (E2), or an empty tubing (blank) and compared to intact naive and experienced male rats. None of the naive animals, whether castrated or intact, showed a consistent preference for any of the four stimuli. Whereas when sexually experienced, only intact and T-treated males showed a female-oriented preference. In the second experiment, the animals were allowed to choose between an active male and an estrous female. Castrated naive male rats were implanted with either T, E2, or DHT, or injected daily SC with the synthetic nonaromatizable androgen, methyltrienelone (R 1881). Two groups of intact males, one consisting of experienced and the other of naive animals, were also included in this experiment. The experienced intact males showed a significant preference for the estrous female, while the intact naive males showed no preference for either of the two stimuli. After the animals had gained heterosexual experience, intact and androgen-treated males showed a significant preference for the female. Neither the administration of R 1881 nor E2 promoted a female-oriented behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗