[Search for better asthma drugs in many research projects. Increasing mortality and underdiagnosing are alarming].
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Asthma↗
Biomedical subjects
K Larsson
Publications and source records attributed to K Larsson.
Effects of selective dopamine D1 and D2 antagonists on male rat sexual behavior.
The effects of selective dopamine (DA) D1 and D2 antagonists on male rat sexual behavior were investigated. The D1 antagonist (+)SCH-23390, 25-100 micrograms kg-1 s.c. -20 min, and the D2 antagonist raclopride, 0.1-1.6 mg kg-1 s.c., -20 min, decreased both the number of mounts and intromissions preceding ejaculation. No statistically significant effects in the time up to ejaculation or in the time up to the first intromission were noted, whereas both compounds produced a statistically significant increase in the post-ejaculatory interval. The effect can generally be characterized as psychomotor inhibition, and no evidence was obtained for a specific role of DA D1 or D2 receptors in the mediation of male rat sexual behavior.
Animals↗
Influence of environmental events immediately after birth on postnatal testosterone secretion and adult sexual behavior in the male rat.
A rise in plasma testosterone (T) levels occurs in male rats during the first 2 hr after birth which is of importance for the process of sexual differentiation. To study the influence of environmental factors on the postnatal T surge and sexual development, newborn male rats were subjected to various treatments immediately after cesarean delivery including cooling, ether anesthesia, and mother-infant separation. In adulthood, the animals were observed for masculine and feminine sexual behavior. Males anesthetized at 0 hr showed elevated levels of feminine sexual behavior and impaired masculine sexual behavior. Pups subjected to cooling or mother-infant separation showed slightly prolonged intromission latencies, but otherwise normal levels of feminine sexual behavior. Significantly elevated plasma T levels were found in intact pups 2 hr after birth but not in pups subjected to cooling or ether anesthesia. Significantly higher levels of T were observed in pups subjected to cooling 4 hr after birth, suggesting a delay of the T surge. The most pronounced impairing effects were seen in the defeminization process, but the masculinization process also is affected by ether anesthesia. It was concluded that ether anesthesia immediately after birth may permanently interfere with the sexual development by suppressing the neonatal T surge.
Animals↗
High- and low-affinity antibodies--some observations in relation to polyethylene glycol concentration in immunoturbidimetric assays.
In an immunoturbidimetric assay it is generally accepted that by increasing the polymer concentration the turbidimetric response is increased when all the other parameters are constant. This is true when working with low-affinity antibodies. When working with high-affinity antibodies some assay systems will produce dose-response curves showing decreasing responses with increasing polymer concentrations. These observations are discussed in relation to the time-course of formation of antigen-antibody complexes.
Antibodies↗
Beta-adrenoceptors in human alveolar macrophages isolated by elutriation.
1. beta-adrenoceptors on human alveolar macrophages obtained by bronchoalveolar lavage (BAL) from healthy smoking volunteers (n = 26) were characterized by studying cyclic AMP (cAMP) accumulation in intact macrophages evoked by adrenaline or isoprenaline, with or without appropriate antagonists and by radioligand binding to macrophage membranes, using [125I]-iodopindolol (125IPIN) as beta-adrenoceptor ligand. 2. In a second study, cAMP responses of alveolar macrophages to isoprenaline and PGE1 and of peripheral blood lymphocytes to isoprenaline were compared in smoking and non-smoking healthy volunteers (n = 9 + 9), as our initial studies were performed in smokers, due to their higher cell yield. 3. BAL yielded 47 +/- 23 x 10(6) cells in smokers and 12 +/- 6 x 10(6) cells in non-smokers with a recovery of 82 +/- 8% in the elutriation step (means +/- s.d.). The cell preparation consisted of 99.2 +/- 0.8% macrophages and their viability (trypan blue exclusion) was 97.5 +/- 5.2%. 4. Isoprenaline or adrenaline increased cAMP accumulation approximately 40-fold with or without the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX, 10(-4) M), which enhanced basal and stimulated cAMP accumulation approximately five-fold. Peak responses were seen after 2 min. EC50s for isoprenaline and adrenaline were 3-5 x 10(-7) M. Phentolamine did not alter responses to adrenaline, indicating absence of inhibitory alpha 2-adrenoceptors. Propranolol inhibited isoprenaline induced cAMP accumulation stereoselectively; pD2-values were 8.2 for (-)-propranolol, 5.6 for atenolol and 7.5 for ICI 118,551, suggesting a predominance of beta 2-adrenoceptors. 5. Specific 125IPIN binding to macrophage membranes was rapid and saturable. Non-specific binding was determined in the presence of 1 microM (-)-propranolol. KD values were 71 +/- 7 pM and the density of specific binding sites was 36 +/- 3 fmol mg-1 protein (three experiments on a membrane pool from 10 subjects; r values for Scatchard analyses = 0.98 +/- 0.01). Similar values were obtained when 200 microM isoprenaline (+ GTP) was used to assess non-specific binding. Competition experiments again showed stereoselectivity for propranolol and a predominance of beta 2-adrenoceptors, as judged by the displacement of specific 125IPIN binding by atenolol and ICI 118,551. 6. Macrophages from smokers responded with less marked cAMP accumulation upon stimulation with isoprenaline or PGE1 than did cells from non-smokers (difference approximately 30%; P less than 0.05 for both agonists) in the presence of IBMX. Thus macrophages from smokers may produce less cAMP due to post-receptor changes in responsiveness.(ABSTRACT TRUNCATED AT 400 WORDS)
1-Methyl-3-isobutylxanthine↗
Ultrastructure of the uterotubal junction in preovulatory pigs.
The ultrastructure of the surface epithelia from the uterotubal junction (UTJ), and the adjacent tubal isthmic and endometrial regions, was studied in preovulatory oestrus gilts, either unmated or inseminated 12 h before with fresh boar semen. The simple columnar epithelium of the UTJ consisted of non-ciliated (secretory) and ciliated cells. Secretory vesicles occurred in the secretory cells, especially in inseminated gilts. Lymphocytes, monocytes and macrophages were found dispersed basally among the epithelial cells. Phagocytosis of epithelial cells undergoing apoptosis was seen throughout the UTJ at oestrus, increasing after insemination. Neutrophilic granulocytes were found in the lamina propria of the uterine component of the UTJ, but only occasionally in the epithelium. After insemination, neutrophils invaded the uterine epithelium, to actively participate in intraepithelial phagocytosis or move into the lumen, engulfing spermatozoa. Neutrophils were absent from the UTJ proper and the isthmic epithelium, irrespective of the presence of spermatozoa in the lumen. Those spermatozoa in the uterine lumen that escaped phagocytosis had severely damaged plasma membranes, whereas those in the UTJ proper--concentrated towards the deep furrows of the diverticulae--mostly showed normal sperm ultrastructure.
Animals↗
Effects of an inhaled corticosteroid, budesonide, on alveolar macrophage function in smokers.
Selected functions of alveolar macrophages obtained by bronchoalveolar lavage of 12 healthy smokers were examined before and after eight weeks' treatment with an inhaled glucocorticosteroid, budesonide (400 micrograms twice daily). After budesonide treatment spontaneous as well as opsonised zymosan triggered prostaglandin E2 (PGE2) secretion from harvested cells was reduced; no such reduction in opsonised zymosan triggered leukotriene B4 (LTB4) production was observed. Neither the capacity to phagocytose opsonised yeast particles nor the superoxide radical generation triggered by the calcium ionophore A23187, 4 beta-phorbol 12-myristate 13-acetate (PMA), or opsonised zymosan ex vivo were more than marginally affected by the glucocorticosteroid treatment in vivo. Lavage fluid concentrations of angiotensin converting enzyme (ACE), however, after treatment were twice those before treatment and concentrations of fibronectin were reduced to half. Albumin concentrations in lavage fluid were not affected by the glucocorticosteroid treatment. In separate experiments treatment of alveolar macrophages with 10(-7) or 10(-6) M budesonide overnight in vitro did not affect their superoxide radical or PGE2 generation but significantly blocked LTB4 release. These data indicate that inhaled gluco-corticosteroid treatment may affect synthesis or release (or both) of ACE and fibronectin by alveolar macrophages from healthy smokers whereas other functions of these cells, such as the generation of reactive oxygen derived products ex vivo, are only marginally affected.
Administration, Inhalation↗
Airways responses to ipratropium bromide do not vary with time in asthmatic subjects. Studies of interindividual and intraindividual variation of bronchodilatation and protection against histamine-induced bronchoconstriction.
Bronchial histamine provocation tests were performed in nine patients with nonallergic asthma on four consecutive days 45 minutes after inhalation of placebo or ipratropium bromide in a dose-response manner (40 micrograms, 200 micrograms, and 800 micrograms). The drugs were administered double-blind, one dose on each day. This procedure was repeated identically after three to nine months to investigate whether the bronchial responses to ipratropium bromide are constant or change with time. Ipratropium bromide induced a significantly better bronchodilation and protection against histamine-induced bronchoconstriction than placebo with no differences between the three doses. No correlation between bronchodilatation and protection was found. In six asthmatic patients ("responders") ipratropium bromide induced a significant protective effect against histamine-induced bronchoconstriction but no dose-response relationship was found. In three patients none or a very poor protective effect was found at all dose levels ("nonresponders"). The protective effect of ipratropium bromide against histamine-induced bronchoconstriction did not differ between the first and second occasion. Thus, the bronchoprotection differed between different asthmatic subjects but did not vary with time (three to nine months) within the same subject. This finding seems to be of clinical importance since it implicates that the effect of anticholinergic agents on the airways is predictable.
Administration, Inhalation↗
Acute bronchoconstriction is not a stimulus for sympatho-adrenal activation in asthmatic or healthy subjects.
Bronchoconstriction has been found to cause little sympathoadrenal activation in asthmatic patients. It has been questioned whether this is due to blunted sympatho-adrenal reactivity in asthmatics or if bronchoconstriction is a stimulus for sympatho-adrenal activation at all. We therefore compared sympatho-adrenal responses in eight asthmatic patients and 12 healthy subjects by measurements of plasma adrenaline and noradrenaline concentrations before, during and after methacholine-induced bronchoconstriction. Significant bronchoconstriction was obtained in eight of the healthy subjects and in all of the asthmatics. Considerably higher concentrations of methacholine were required to evoke bronchoconstriction in the healthy subjects but the relative magnitudes of bronchoconstriction were similar in the two groups: peak expiratory flow (PEF) decreased by approximately 24 and approximately 28% and specific airway conductance (sGaw) decreased by approximately 68 and approximately 70% in asthmatics and controls, respectively). Methacholine-induced bronchoconstriction did not alter plasma catecholamine levels significantly in either group. In addition, plasma concentrations of catecholamines and neuropeptide Y-like immunoreactivity (NPY-LI) were measured before and during bronchoconstriction induced by histamine or allergen in 8 and 5 asthmatic subjects, respectively. Plasma noradrenaline, adrenaline and NPY-LI remained unchanged up to 30 min after bronchoconstriction induced by histamine or allergen. We, therefore, conclude that bronchoconstriction is not a stimulus for sympatho-adrenal activation and that the lack of an adrenaline response to bronchoconstriction is not likely to be related to NPY release.
Acute Disease↗
[Do patients with uremia receive sufficient health care? Varying estimations of the need for dialysis].
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Aged↗
Effects of local application of 5-HT into the median and dorsal raphe nuclei on male rat sexual and motor behavior.
The local application of 10 micrograms 5-hydroxytryptamine (5-HT) into the dorsal or median raphe nucleus was found to facilitate male rat sexual behavior, as evidenced by a decrease in time to ejaculation, and in number of intromissions preceding ejaculation. The application of a higher dose, 40 micrograms, at either site, inhibited the initiation of sexual behavior. There was a clear distinction between the motor effects observed after local application of 5-HT into the dorsal or the median raphe nuclei. Injections into the median raphe produced a dose-dependent increase, whereas injections into the dorsal raphe nucleus produced a dose-dependent decrease, in motor activity. Present results suggests an inhibitory and excitatory role of the median and the dorsal raphe serotonergic projections, respectively, as regards motor behavior, whereas projections from both nuclei appear to have an inhibitory role in the mediation of male rat sexual behavior.
Animals↗
Evidence for the involvement of central 5-HT1A receptors in the mediation of lordosis behavior in the female rat.
5-Hydroxy-L-tryptophan (5-HTP), 25 mg kg-1 IP, in combination with the peripheral 5-HTP decarboxylase inhibitor benserazide, 25 mg kg-1 IP, and the selective inhibitor of neuronal 5-hydroxytryptamine (5-HT) re-uptake, zimeldine, 10 mg kg-1 IP, suppressed lordosis in ovariectomized female rats, treated with estradiol benzoate (EB) or with EB plus progesterone (P). The suppression of lordosis produced by 5-HTP was antagonized by the beta-receptor blocker (-)pindolol, which also is a selective 5-HT1 receptor antagonist, but not by the 5-HT2 receptor antagonists metitepine or pirenperone, nor by the beta-receptor blocker betaxolol. The EB- or EB plus P-activated lordosis was also suppressed by administration of the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Together, these observations indicate an important role of central 5-HT1A receptors in the mediation of lordosis behavior in the female rat.
5-Hydroxytryptophan↗
99mTc-DTPA clearance measured by a dual head gamma camera in healthy subjects and patients with sarcoidosis. Studies of reproducibility and relation to bronchoalveolar lavage findings.
99mTc-DTPA clearance was studied in ten healthy non smokers, five asymptomatic smokers and nine non smoking patients with sarcoidosis in the supine position with a dual head gamma camera allowing simultaneous information of regional clearance rates in frontal and dorsal projections. In the patients with sarcoidosis, a bronchoalveolar lavage was performed prior to the clearance study. DTPA clearance rate was measured during 60-90 min and data were corrected for recirculating radioactivity. The coefficients of variation for measurements on 2 consecutive days in the 10 healthy non smokers were 9%-11% for the right and left lung, anterior and posterior projections. The T1/2 calculated from total lung projections were 90-92 min for the anterior view and 84-85 min for the posterior view. Regional measurements did not add further information. No apico-basal difference was found but there was a significant fronto-dorsal gradient in 99mTc-DTPA clearance in the supine position. Smokers had significantly (P less than 0.01) faster clearance rates (T1/2 28 +/- 10 min) than healthy controls. In the sarcoidosis group clearance rates were increased in four patients and no relationships were found between DTPA clearance rates and inflammatory markers (lymphocytes, albumin, ACE) in the bronchoalveolar lavage fluid.
Adult↗
Antagonism by pindolol, but not betaxolol, of 8-OH-DPAT-induced facilitation of male rat sexual behavior.
8-OH-DPAT (0.25 mg/kg s.c.) produced a facilitation of the male rat sexual behavior, characterized by a decrease in the number of intromissions preceding ejaculation and in the time to ejaculation. This facilitation of the sexual behavior was antagonized by administration of the 5-HT and beta-adrenoceptor antagonist pindolol (4 mg/kg i.p.), but not by the selective beta-adrenoceptor antagonist betaxolol (4 mg/kg i.p.). Neither pindolol (2-8 mg/kg), nor betaxolol (2-8 mg/kg), produced any statistically significant effects per se on the male rat sexual behavior, as observed here (mounts, intromissions, ejaculation latency or the post-ejaculatory interval). A higher dose (16 mg/kg) of betaxolol produced a statistically significant reduction in the number of intromissions preceding ejaculation and in the ejaculation latency. The antagonism by pindolol of 8-OH-DPAT-induced effects on male rat sexual behavior suggests an involvement of 5-HT1A receptors in the facilitation of this behavior produced by 8-OH-DPAT.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Effects of stereoselective 5-HT1A agonists on male rat sexual behavior.
The effects on male rat sexual behavior of some new stereoselective 5-HT agonists, related to 8-OH-DPAT, are presented. It was found that (+)cis-8-hydroxy-1-methyl-2-(di-n-propylamino) tetralin (8-OH-MeDPAT), as well as (-)trans-2-(2-hydroxyphenyl)-N,N-di-n-propylcyclopropylamine (2-OH-DCPA), and its 3-hydroxy-phenyl analog (3-OH-DCPA), stereoselectively facilitated the male rat sexual behavior, as evidenced by a decrease in the number of intromissions preceding ejaculation, and a shortening of the ejaculation latency. For the former two compounds, studied in further detail, the potency and efficacy appear to be of the same magnitude as previously found for 8-OH-DPAT. The results demonstrate specific 5-HT receptor involvement in the mediation of male rat sexual behavior.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Effects of chronic and acute ethanol treatment during prenatal and early postnatal ages on testosterone levels and sexual behaviors in rats.
This study was prompted by previous findings that prenatal ethanol exposure may interfere with the differentiation of the sexual behavior in rats. Ethanol (6 g/kg) administered daily from day 15 postconception, resulted in elevated testosterone (T) levels on Day 18 in male and female fetuses. No alterations of sexual behavior in the ethanol-treated male offspring were seen under these conditions. However, in ethanol-treated female offspring the onset of regular estrous cycling was significantly delayed. Acute treatment with doses of ethanol, 2, 4 or 6 g/kg, was ineffective in influencing plasma T levels of the fetuses. Acute treatment with 3 g/kg ethanol did not prevent the rise of T levels normally occurring immediately after birth. In adulthood, but not at prepubertal age (Day 30), treatment of male rats with 2 g/kg ethanol caused a depression of plasma T levels. Possible mechanisms affected by ethanol exposure and influencing on the fetal development were discussed.
Age Factors↗
Sympatho-adrenal activity is assessed in patients with asthma by measurements of catecholamines and neuropeptide Y-like immunoreactivity (NPY-LI) in venous plasma.
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Adrenal Glands↗