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K Larsson

Publications and source records attributed to K Larsson.

At least 181 records · Page 10Linked to original sources

Pulmonary gas exchange response following allergen challenge in patients with allergic asthma.

Pulmonary gas exchange was studied in 8 patients with allergic asthma before and after allergen challenge. Ventilation-perfusion relationships were assessed by the multiple inert gas elimination technique and forced expiratory flow by conventional spirometry. Measurements were made before, 7-8 minutes, and 0.5, 2.5 and 5 hours after challenge. During baseline conditions all patients showed normal forced expiratory flow (FEV1 3.9 +/- 0.77 (SD) l) and gas exchange expressed as the dispersion of pulmonary blood flow, log SDQ (0.35 +/- 0.08), (one of the common descriptors of ventilation-perfusion (VA/Q) inequality). Immediately after challenge there were significant decreases in FEV1 (to 2.3 +/- 0.75 l) and arterial PO2 (from 13.1 +/- 0.9 to 9.5 +/- 1.2 kPa). The developed ventilation-perfusion inequalities were similar to those found in other asthma studies, i.e. mainly a broad (log SDQ increased to 0.73 +/- 0.30) and sometimes bimodal distribution of the perfusion. Thirty minutes after challenge FEV1 significantly improved to 3.2 +/- 1.18 l while log SDQ remained high (0.71 +/- 0.32). Two and a half hours after challenge log SDQ was reduced and almost normalized to 0.38 +/- 0.07. Five patients developed a late phase reaction with decreasing flow rates after 5 hours. Three of these patients also showed increased log SDQ. There was no clear relationship between gas exchange mismatch and reduced forced expiratory flow. The results support the hypothesis that reduced expiratory flow and gas exchange impairment are caused by different pathophysiological mechanisms.

Adolescent↗

Effects of sexual interactions on the in vivo rate of monoamine synthesis in forebrain regions of the male rat.

The effects of heterosexual interactions on the in vivo rate of regional brain monoamine synthesis were examined in the male rat. To this end, the animals were administered an inhibitor of cerebral aromatic L-amino acid decarboxylase, NSD-1015 (100 mg.kg-1 i.p.), and regional brain DOPA and 5-HTP accumulation, over a 15-35 min period of sexual interaction, was compared with the DOPA or 5-HTP accumulation in time-matched home cage controls. Using the DOPA and 5-HTP accumulation as an estimate for the rate of tyrosine and tryptophan hydroxylase activity, respectively, the present results demonstrate: (1) an increased demand on catecholamine synthesis in the neocortex, the amygdala and in the septal area; and (2) an increased dopamine and serotonin synthesis in the ventral striatum (excluding the olfactory tubercle), and in the dorsal striatum.

5-Hydroxytryptophan↗

Behavioral and biochemical effects of the 5-HT1A receptor agonists flesinoxan and 8-OH-DPAT in the rat.

The 5-HT1A receptor agonists flesinoxan (0.2-3.2 mg kg-1 s.c.) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.025-0.4 mg kg-1 s.c.) produced (1) a dose-dependent facilitation of male rat ejaculatory behavior and (2) characteristic, dose-dependent effects on spontaneous motor activity. Thus, total locomotor activity and rearing activity were decreased. However, forward locomotion and peripheral locomotion were increased relative to the total horizontal activity. Furthermore, (3) 5-HTP accumulation, after inhibition of cerebral decarboxylase, was dose dependently decreased by both compounds in the ventral striatum and in the prefrontal cortex. There was a statistically significant decrease in DOPA accumulation in the ventral striatum after administration of a high dose of flesinoxan (3.2 mg kg-1), and a tendency for 8-OH-DPAT to produce the same effect. The efficacy of the compounds to affect male rat sexual behavior, spontaneous motor activity in the open-field and forebrain 5-HT synthesis was approximately the same, whereas flesinoxan was about an order of magnitude less potent than 8-OH-DPAT.

5-Hydroxytryptophan↗

Region-selective inhibition of male rat sexual behavior and motor performance by localized forebrain 5-HT injections: a comparison with effects produced by 8-OH-DPAT.

The local application of 5-HT (0-40 micrograms side-1) into the nucleus accumbens was found to inhibit male rat sexual behavior, as evidenced by an increase in number of mounts and intromissions preceding ejaculation and in time to ejaculation. There were no effects on male rat sexual behavior after similar 5-HT injections into other striatal areas, including the dorsolateral, the ventromedial and the posterior neostriatum, as well as the olfactory tubercle. The same groups of animals were also scored for motor activity and body posture after the injection of 5-HT, and only animals injected into the nucleus accumbens showed a statistically significant decrease in motor activity and an increase in the display of a flat body posture. 8-OH-DPAT (0-5 micrograms side-1), injected into the nucleus accumbens, produced a facilitation of the male rat sexual behavior, as evidenced by a decrease in number of mounts and intromissions to ejaculation, as well as in the postejaculatory interval. 8-OH-DPAT injections into the nucleus accumbens produced a decrease in motor activity and an increase in the per cent animals with a flat body posture. Injections into the olfactory tubercle had no effects on the sexual behavior or on the motor activity, whereas the per cent flat body posture was increased. Local application of 8-OH-DPAT (0-5 micrograms) into the median raphe nucleus, facilitated male rat sexual behavior, as evidenced by a decrease in number of intromissions preceding ejaculation and in time to ejaculation. The same doses of 8-OH-DPAT injected into the dorsal raphe had no effects on the sexual behavior. In an additional experiment, 3 groups of animals were injected with 5-HT (40 micrograms) or 8-OH-DPAT (5 micrograms) into the nucleus accumbens, the dorsal and the median raphe nuclei and thereafter observed for treadmill performance. No statistically significant effects were found after injections in any of these brain areas. The present results strongly suggest an inhibitory role of ventral forebrain 5-HT in the mediation of male rat sexual behavior. The facilitation produced by 8-OH-DPAT is possibly due to a blockade of 5-HT2 receptors. Facilitation by 8-OH-DPAT of the male rat copulatory performance after median raphe injections is probably due to stimulation of 5-HT1A autoreceptors in this brainstem region. In contrast to their opposite effects on sexual behavior, both compounds produced a decrease in motor activity and an increased display of flat body posture after accumbens injections.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Synthetic human calcitonin in postmenopausal osteoporosis: a placebo-controlled, double-blind study.

A placebo-controlled, double-blind study was carried out over 4 months to evaluate two doses of synthetic human calcitonin (0.25 and 0.125 mg) given s.c. three times per week. Enrolled were 60 women, aged 56-82 years, who had experienced a vertebral fracture due to low-energy trauma within the preceding year. During active treatment there was within the first month a dose-dependent decrease of the indices of bone resorption (fasting urinary calcium and hydroxyproline excretions), whereas only the higher dose and a treatment period of 4 months produced a reduction of bone formation (serum osteocalcin). The bone mineral content (BMC) of the nondominant forearm was unchanged. Treatment with calcitonin also had significant, dose-dependent, analgetic effects. The amelioration of pain was, in multivariate analyses, related to a reduction in parameters felt to be markers for bone resorption. In the placebo group there was a significant reduction of the BMC of the forearm but no changes of any of the biochemical markers for bone turnover and no improvement of pain. In conclusion, treatment with two low doses of calcitonin induced changes of the biochemical markers of bone turnover in a dose-dependent manner. The analgetic properties of calcitonin were also of salient clinical importance. The knowledge derived from this study could be adapted to the dosage schedule in long-term trials in osteoporosis.

Aged↗

Synergistic action of estradiol, progesterone and testosterone on rat proceptive behavior.

The role of estradiol (E), progesterone (P) and testosterone (T) in the control of rat feminine sexual behavior (receptivity, proceptivity and sexual orientation) was analyzed. The action of estradiol benzoate (EB, 1.25 micrograms/rat x 3 days) and P (0.5 mg/rat) was compared in ovariectomized (OVX) and ovariectomized-adrenalectomized (OVX + ADX) subjects. Administration of EB alone was followed by maximum levels of lordosis behavior and a male-directed orientation in both OVX and OVX + ADX females. A reduction in the level of proceptivity was observed in EB-treated OVX + ADX animals as compared with EB-treated OVX rats. The administration of P to OVX + ADX females resulted in an increase in proceptive behavior similar to that observed in OVX EB-treated animals. A further study analyzed the effect of combined administration of EB, P and various doses of T (30, 90 and 270 micrograms/rat) in OVX + ADX rats. A synergistic action of all three hormones on proceptivity was observed. Neither a further increase in lordosis nor in male-directed orientation was observed in EB-treated females after additional treatment with P or T independently or together. Finally, we studied the effect of adrenalectomy on the spontaneous onset of estrous behavior. Adrenalectomy did not modify any aspect of normal feminine sexual behavior, suggesting that the adrenals, in the presence of the ovaries, are of no critical importance for this behavior. The possible contribution of adrenal steroids to the expression of proceptivity is discussed.

Adrenalectomy↗

Role of androgen, estrogen and sexual experience on the female rat's partner preference.

Virgin ovariectomized rats were implanted with Silastic tubings containing estradiol (E2, 5 mm), testosterone (T, 30 mm), dihydrotestosterone (DHT, 30 mm), or injected daily SC with the synthetic nonaromatizable androgen, methyltrienelone (R 1881, 5 mg.kg-1) daily for three weeks. Animals were tested for partner preference behavior (staying in the vicinity of a sexually active male, an estrous female or staying elsewhere) before and after they had been tested for feminine and masculine sexual behavior. All naive androgen-treated groups showed a male-oriented preference, while the naive E2-treated females did not show any consistent partner preference. Sexual experience abolished the male-directed orientation of the androgen-treated groups while E2 treatment induced a male-directed orientation. E2-treated females spent significantly longer time elsewhere in both tests compared to the other groups which might be due to insufficient levels of E2. Feminine sexual behavior was seen after treatment with E2 or T but not after treatment with DHT or R 1881. It was concluded, 1) that the effect of treatment with an androgen on the partner preference behavior differs according to whether the females are virgins or sexually experienced, and 2) the effect of the hormone treatment on the partner preference behavior is independent of whether the hormone stimulates feminine sexual behavior.

Androgens↗

Opposite effects of 5-methoxy-N,N-di-methyl-tryptamine and 5-hydroxytryptophan on male rat sexual behavior.

The administration of 5-methoxy-N,N-di-methyl-tryptamine (5-MeODMT), O-2.0 mg.kg-1 SC -15 min, produced a dose-dependent facilitation of the male rat sexual behavior, as evidenced by a decrease in the number of intromissions to ejaculation and in the ejaculation latency. The effects produced by 5-MeODMT (1 mg.kg-1) were antagonized by pindolol (4 mg.kg-1 SC -30 min), but not pirenperone (0.25 mg.kg-1 SC -30 min) or metergoline (1 mg.kg-1 SC -30 min), administration. As expected, 5-HTP (25 mg.kg-1 SC -60 min) produced an increased number of mounts and intromissions to ejaculation and an increase in the ejaculation latency in benserazide (25 mg.kg-1 SC -90 min) pretreated animals. Pindolol (4 mg.kg-1) by itself produced the same effects as seen after 5-HTP administration, and the combination of these compounds produced additive effects. Betaxolol (8 mg.kg-1 SC -30 min) had no effects of its own and did not interact with 5-HTP. The results suggest that stimulation of brain 5-HT1 or 5-HT2 receptors produces facilitation and inhibition, respectively, of the male rat sexual behavior.

5-Hydroxytryptophan↗

Anxiolytics reverse the acceleration of ejaculation resulting from enforced intercopulatory intervals in rats.

The enforced interval of copulation (EIC) consists of the artificial prolongation of the interintromission interval, induces a reduction in the number of intromissions preceding ejaculation, and is accompanied by an anxiety like behavioral repertoire. The administration of the benzodiazepine anxiolytics diazepam, chlordiazepoxide, flurazepam, and flunitrazepam produced a dose-dependent inhibition of the EIC effect with a concomitant increase in mounting. These actions were blocked by the central benzodiazepine antagonist Ro 15-1788. The anxiogenic agent beta-carboline Zk 39106 had no effect. Treatment with pentobarbital also produced a blockade of the reduction in the number of intromissions during EIC, whereas muscimol and bicuculline lacked this effect. The serotonergic anxiolytic buspirone reversed the facilitatory action induced by EIC; however, two putative serotonergic antianxiety agents, 8-OH-DPAT and ipsapirone, did not modify or potentiate it, respectively. Finally, the nonanxiolytic serotonergic compounds 5-hydroxytryptophan and TFMPP drastically increased the number of mounts but did not antagonize the reduction of intromissions produced by EIC. These results suggest that an increase in the anxiety levels may be responsible for the excitatory action of EIC on sexual behavior.

Adrenergic alpha-Agonists↗

Skeletal responsiveness to parathyroid hormone in healthy females: relationship to menopause and oestrogen replacement.

In order to directly evaluate the role of parathyroid hormone (PTH) and its interaction with oestrogens for postmenopausal bone loss, studies were performed where synthetic human (1-38) PTH was infused s.c. over 24 h in 15 healthy females. Measurements were made of serum electrolytes, PTH and biochemical indices of bone turnover: serum osteocalcin and alkaline phosphatase and fasting urinary hydroxyproline and calcium. During the infusion of PTH there were significant increases of serum calcium (15%), fasting urinary calcium (55%) and hydroxyproline (80%) but a reduction of the serum osteocalcin concentrations (15%). There were significant relations between the calcaemic response and the increases of urinary calcium and hydroxyproline and the two latter were also closely related. There was, however, no correlation between the responses to PTH for the formative vs the resorptive indices. Postmenopausal women displayed greater increases of serum calcium and fasting urinary hydroxyproline indicating greater skeletal sensitivity to exogenous PTH. Following treatment with oestrogens the indices of skeletal responsiveness were reversed towards the premenopausal values. The findings demonstrate that during short-term infusion of PTH there is a dissociation between bone resorption and formation and, furthermore, that the menopause is associated with an enhanced skeletal sensitivity for PTH.

Adult↗

Concentrations of nuclear progesterone receptors in endometrium of virgin and repeat breeder heifers after embryo transfer.

The present study aimed to correlate the repeat breeder syndrome in the bovine with an impaired or suboptimal uterine progestational response. Concentrations of nuclear (i.e. transformed) receptors for progesterone (PRn) were determined with a binding and exchange method in endometrial samples from virgin (VH) and repeat breeder (RBH) heifers 15 days post oestrus. The heifers were recipients of Day 7 demi-embryos collected from donors with normal fertility and transferred 8 days prior to tissue sampling. Results were compared with both the type of heifer, the condition of the embryo present within the uterus and the temporal relationship to the hormone plasma levels. The binding data for PRn indicated that a single class of high-affinity, low-capacity sites existed. The amount of PRn in VH endometria holding embryonic structures was significantly greater than in RBH, but no statistical differences were found in their plasma progesterone levels. PRn concentrations were also higher in the uterine horn in which an elongated (greater than 15 mm), morphologically normal embryo was present, when compared to cornua with small (less than 5 mm) embryos, regardless of recipient group. Furthermore, in endometria with an elongated embryo in the lumen, the relative amount of PRn was significantly greater in VH than in RBH. The present results indicate that the RBH recipients of Day 7 demi-embryos by Day 15 have fewer numbers of specific receptors for maternal progesterone, which could explain in part the poorer development of the transferred embryos compared with that in virgin heifers.

Animals↗

Sperm morphology and fertility in A.I. bulls.

Forty-seven A.I. bulls between 15 and 26 months of age, were used to study the relationship between sperm morphology in fresh semen and fertility (56-day non-return rate) in frozen semen following 11,749 inseminations. The sperm morphology was studied in two freezing operations/bull in a phase-contrast microscope and morphological abnormalities were recorded as a percentage of the total number of counted spermatozoa. Morphological categories used in this study were abnormal heads, detached heads, nuclear pouches, abnormal acrosomes, proximal cytoplasmic droplets, abnormal midpieces and abnormal tails. The greatest mean value recorded for the investigated categories was found for abnormal heads (3.8%) but the majority of morphological abnormalities only occurred in about 1% of all studied spermatozoa. Breed effects were found, with a somewhat higher incidence (p less than or equal to 0.05-0.01) of sperm abnormalities and poorer fertility among SRB than among SLB bulls. Despite the low frequency of sperm abnormalities, statistically significant (p less than or equal to 0.05-0.001) correlations were found between abnormal heads, nuclear pouches and proximal cytoplasmic droplets assessed in fresh semen and fertility (56-day non-return rate) of frozen semen.

Animals↗

Short-term effects of pamidronate on biochemical markers of bone metabolism in osteoporosis--a placebo-controlled dose-finding study.

The bisphosphonates are potent inhibitors of osteoclastic bone resorption that mainly have been used for treatment of hypercalcaemia secondary to malignancy. We have performed a controlled dose-finding study of oral pamidronate that was given to 60 patients with a history of fracture of the distal forearm, an enhanced bone turnover and a lowered bone mineral density. Different doses of pamidronate, 75 mg and 150 mg daily, or placebo were given to parallel groups. Fasting specimens of blood and urine were collected before the treatment period and at regular intervals. Oral pamidronate caused a dose-related reduction on the biochemical markers of bone resorption, i.e. fasting urinary calcium, hydroxyproline, pyridinoline and deoxypyridinoline that was seen already after the first week. The inhibition was evident during the treatment period and 4 weeks thereafter but not 12 weeks after cessation of therapy. Also the levels of serum osteocalcin, a marker of bone formation, were lowered during treatment with the higher dose.

Administration, Oral↗

Structure of the starch granule--a curved crystal.

A structure model of the molecular arrangement in native starch proposed earlier is further considered, with special regard to the lateral packing of cluster units. The amylopectin molecules are radially distributed, with branches concentrated in clusters. Within each cluster the polyglucan chains form double helices which are hexagonally packed. The clusters form spherically concentric crystalline layers with amylose in an amorphous form acting as a space-filler. A translational mechanism for the change of helical direction at boundaries between clusters is proposed which can account for variations in the curvature of the concentric layers. The model is related to X-ray diffraction data and optical birefringence, considering dissembly at gelatinization. The structure is also discussed in relation to biosynthesis. Some aspects of gelatinization, such as the recent glass-transition approach, are then considered.

Amylopectin↗

Disturbance of basal and stimulated serum levels of intact parathyroid hormone in primary hyperparathyroidism.

In patients with primary hyperparathyroidism, measurements were made of basal and stimulated levels of intact parathyroid hormone (PTH). The basal PTH values were elevated in all but six of 89 patients and provided clear separation towards normal individuals (n = 75) and patients with hypercalcemia of other origin (n = 34). The PTH value correlated with the serum calcium concentration in hyperparathyroidism and with the weight of excised parathyroid adenomas but not with that of chief cell hyperplasias. A constant ethylenediaminetetraacetic acid infusion during 60 minutes of induced essentially linear reductions of plasma-ionized calcium concentrations, averaging 0.02 mmol/L/10 minutes, which were associated with swift, curvilinear, elevations of PTH levels that reached a plateau after 10 to 20 minutes. The increment in serum PTH level correlated with the basal PTH value both in patients with hyperparathyroidism and controls. However, in proportion to the much greater glandular mass in the patients with hyperparathyroidism, the secretion of PTH was relatively reduced. The findings support the value of the intact PTH assay in the differential diagnosis of hypercalcemia and show that PTH secretion in vivo is extremely sensitive to hypocalcemic stimulation, that the pathological parathyroid tissue in hyperparathyroidism is characterized by a reduction of hormone release per unit weight, and that the hormone secretion in hyperparathyroidism operates closer to its maximal capacity than under normal circumstances.

Adult↗

Increased lung deposition and biological effect of methacholine by use of a drying device for bronchial provocation tests.

A simple device aiming to increase deposition of nebulized methacholine in the lower airway was studied. The device controlled inspiratory flow and volume and dried the aerosol. The effect of drying on deposition in the throat and lower airways was studied in six subjects given an aerosol of 99mTechnetium-diethylenetriamine pentaacetate (DTPA) in saline with the device and with a reference device giving the same inspiratory flow and volume but no drying. Drying reduced throat deposition from 46 (range 26-61) to 13 (range 6-22)% (p less than 0.05) of the inhaled and retained dose. The effect of drying on the biological effect of nebulized methacholine was studied in 21 subjects who underwent three provocation tests on different days with doubling concentrations of methacholine from 0.5 to a maximum of 64 mg.ml-1, one with the reference device and two with the drying device. The percentage change in forced expiratory volume in one second (%FEV1) per cumulative dose of methacholine changed from -1.0 (2.6) %FEV1.mumol-1 (geom. mean and SD) with the reference device to -1.6 (3.6) with the drying device p less than 0.02. In an additional study 20 subjects underwent four provocation tests on different days, two with a different version of the drying device and two with the reference device. The slope changed from -1.1 (3.1) to -1.6 (3.3), p less than 0.02. The reproducibility of duplicate measurements did not improve with the drying device. Thus, the drying device decreased throat deposition and increased the biological effect of nebulized methacholine.

Administration, Inhalation↗