Salmeterol, formoterol, and salbutamol in the isolated guinea pig trachea: differences in maximum relaxant effect and potency but not in functional antagonism.

BACKGROUND--Formoterol and salmeterol are new long acting beta 2 adrenoceptor agonists. The maximum relaxant effect, potency and functional antagonism against carbachol induced contraction for salmeterol, formoterol and salbutamol have been compared in the guinea pig isolated trachea. In addition, the possibility of inducing a non-beta adrenoceptor mediated relaxation by salmeterol was studied. METHODS--Concentration response experiments were conducted with isolated tracheal preparations (n = 4-6 in all experiments), precontracted by carbachol to cause either 40% (60 nmol/l), 80% (0.3 mumol/l) or 100% (3 mumol/l, supramaximal) of the maximum contraction. Each beta agonist was added cumulatively at each level of precontraction. Additional cumulative concentration response experiments were conducted for salmeterol alone at the highest level of precontraction, with and without beta blockade by sotalol (1 mmol/l). With the drug concentrations which produced the maximum response and the highest level of precontraction, the relaxation of formoterol (10 nmol/l) and salmeterol (1 mumol/l) was also compared non-cumulatively. Finally, with the corresponding drug concentrations and precontraction, the relaxant effect was compared for formoterol (10 nmol/l) in salmeterol relaxed airways with that of salmeterol (1 mumol/l) in formoterol relaxed airways. RESULTS--The increase in carbachol concentration from 60 nmol/l to 3 mumol/l induced a rightward shift in the mean (SE) concentration (log steps) causing 50% maximum relaxation for salmeterol (0.73 (0.17)), formoterol (0.85 (0.18)), and salbutamol (1.13 (0.11)). Significant differences in the maximum relaxant effect were shown at the highest level of precontraction only, with a remaining active tension of percentage precontraction of 27% (4%) for 1 mumol/l salbutamol and 35% (3%) for 10 nmol/l formoterol compared with 50% (2%) for 1 mumol/l salmeterol. The rank order of potency was: formoterol > salbutamol approximately salmeterol at all levels of precontraction (-log EC50: 9.32 (0.05) for formoterol, 7.82 (0.08) for salbutamol, and 7.50 (0.13) for salmeterol at 80% maximum precontraction). Beta blockade by sotalol (1 mmol/l) significantly inhibited the relaxation induced by salmeterol (1 mumol/l) (remaining active tension: 104% (1%) v 71% (11%) of precontraction) but not the relaxation induced by salmeterol (10 mumol/l) (remaining active tension: 75% (5%) v 71% (12%) of precontraction). In the non-cumulative experiments, formoterol displayed more relaxant effect than salmeterol (remaining active tension: 51% (6%) v 65% (6%) of precontraction). Finally, formoterol significantly relaxed salmeterol relaxed airways (relaxant effect: 22% (8%) of precontraction) whereas there was no significant response to salmeterol in formoterol relaxed airways (relaxant effect: 5% (12%) of precontraction). CONCLUSIONS--In the guinea pig isolated trachea, formoterol and salbutamol produce more relaxant effect than salmeterol, suggesting that salmeterol is a partial beta 2 agonist. Very high concentrations of salmeterol may induce non-beta adrenoceptor mediated relaxation. Formoterol is more potent than both salbutamol and salmeterol. There is no pronounced difference in the magnitude of antagonism against carbachol induced contractions between salmeterol, formoterol, and salbutamol.     

Caries experience in Icelandic 12-year-old urban children between 1984 and 1991

Abstract – In order to evaluate trends in caries experience, a 20% random sample of 12-yr-old residents of Reykjavik, Iceland (252 children) was examined clinically and radiographically in 1991 under conditions consistent with those of the survey conducted in 1984. In addition to caries data, frequency of toothbrushing and use of fluoride dentifrice were recorded. The mean DFT and DPS were 3.0 and 4.1, respectively. The decrease in caries experience reached 60% with an annual fall in DPS of nearly 10%. During the 7-yr period between examinations the decline in DFT and DFS scores averaged 5.2 and 8, respectively, the annual reduction amounting to 0.7 DF teeth or 1.1 DF surfaces per child. The ratio of approximal/occlusal caries and the proportion of approximal caries were similar in both surveys. Fourteen percent of the children were free from manifest caries in 1991, but only 2% in 1984. Polarization between low and high prevalence individuals had intensified. Ninety-five percent of the children brushed their teeth regularly and 97% reported using a fluoride dentifrice.     

Pineal response after pyridoxine test in children

Summary To characterize the pineal response to pyridoxine, plasma melatonin was measured in one hundred and twenty children 3 hours after vitamin B₆ administration. The children, aged between 1.5 and 8 years, were divided in four groups as follows: a) control day group, grouping 27 children sampled at 9:00 and at 12:00; b) control night group, grouping 29 children sampled at 21:00 and at 24:00; c) pyridoxine day group, grouping 30 children sampled at 9:00, then intravenously (i.v.) injected with 3mg/kg of pyridoxine, and sampled at 12:00; and d) pyridoxine night group, grouping 34 children sampled at 21:00, i.v. injected with 3mg/kg of pyridoxine, and sampled at 24:00. Melatonin concentration was measured by radioimmuno assay. The data obtained showed a significant increase in melatonin levels after pyridoxine administration in the pyridoxine night group (39.87 ± 8.02pg/ml basal vs 88.45 ± 9.21 pg/ml after pyridoxine, p < 0.001). The other groups did not showed significant differences in melatonin concentrations. Statistical analysis shows that the administration of pyridoxine during the nocturnal hours represents a stimulating factor to increase the pineal production of melatonin in children.     

The prevalence and clinical correlates of apathy and irritability in Alzheimer's disease

We examined the prevalence and correlates of apathy and irritability in a consecutive series of 101 patients with probable Alzheimer's disease (AD). Based on clinical criteria, 46 (46%) patients had apathy, and 13 (13%) patients had irritability. Apathy was significantly associated with more severe impairments in activities of daily living, significantly more severe extrapyramidal signs, and a significantly higher frequency of both major depression and dysthymia. Patients with irritability had significantly more severe impairments in activities of daily living and significantly higher depression and anosognosia scores. On the other hand, neither apathy nor irritability were significantly associated with deficits in specific cognitive domains.     

Fractures after Stroke

Fractures are a serious complication after stroke. Among patients with femoral neck fractures, a large subgroup have had a previous stroke. This study aimed to investigate the incidence of fractures after stroke. Included in the study were 1139 patients consecutively admitted for acute stroke. Fractures occurring from stroke onset until the end of the study or death were registered retrospectively. Hip fracture incidence was compared with corresponding rates from the general population. Patients were followed up for a total of 4132 patient-years (median 2.9 years). There were 154 fractures in 120 patients and median time between the onset of stroke and the first fracture was 24 months. Women had significantly more fractures than men (χ² = 15.6; p < 0.001). In patients with paresis most of the fractures affected the paretic side (χ² = 22.5; p < 0.001) and 84% of the fractures were cause by falls. Hip fracture was the most frequent fracture and the incidence was 2–4 times higher in stroke patients compared with the reference population. Fractures are thus a common complication after stroke. They are usually caused by falls and affect the paretic side. It is necessary to focus on the prevention of post-stroke fractures, including the prevention of both falls and osteoporosis.     

Detection of pathology of the urinary system in students during preventive mass screening

Screening tests including the questionnaire method, urine analysis and radiorenography were used during mass screening of 1330 students. Comparison of the results of the first two methods showed a good informative value of the questionnaire method for the detection of pathology of the kidneys and urinary tracts. Radiorenography performed in 106 students with the detected nephrological symptom complex (risk group) revealed some changes practically in every other "risk group" student.     

Duplication of the right atrioventricular orifice in a patient with common atrium and mitral cleft

The following case involved duplication of the right atrioventricular valve in a patient with a common atrium. The accessory orifice, formed by two fine leaflets, connected the right atrium with the right ventricular outflow tract and had no subvalvular apparatus. Successful surgical correction was accomplished under standard cardiopulmonary bypass.     

Activation of inflammatory systems during cardiopulmonary bypass

"Whole body inflammation" induced by cardiopulmonary bypass may play a role in the pathogenesis of postoperative complications after open-heart surgery. The inflammatory response, in terms of complement activation and release of granular proteins from neutrophil granulocytes, was investigated in six patients undergoing aortocoronary bypass surgery. Complement activation was demonstrated as well as substantially increased plasma levels of lactoferrin and myeloperoxidase--two granulocyte factors. The activation of inflammatory systems probably takes place on the artificial surfaces of the extracorporeal device. The biocompatibility of these components therefore should be further studied.     

Enzymatic synthesis of penicillins

Different penicillins (phenylacetyl, 2-hydroxyphenylacetyl, 4-hydroxyphenylacetyl, phenoxyacetyl and 2-thiopheneacetylpenicillin) have been synthesized "in vitro" by direct N-acylation of 6-aminopenicillanic acid (6-APA) with the acyl group of several acyl-CoA derivatives. The enzyme that catalyzes these reactions, acyl-CoA: 6-APA acyltransferase of Penicillium chrysogenum, was purified to homogeneity (374-fold) and its amino acid composition is given. This protein accepts as substrates several aliphatic acids and different aromatic acids with the only requirement that an acetyl-CoA moiety must be present in the substrate molecule. Shortening or lengthening of the acyl moiety prevents the 6-APA-N-acylation reaction. The presence of an amino group in the alpha-position of the acetyl group does not allow this molecule to be used as substrate. However, different substitutions in the phenyl group (hydroxylation of the carbons 2 and 4) or its replacement by another aromatic ring (thiophene) were accepted with varying reactions rates in the acylation reaction when a 176-fold purified acyltransferase was employed. The homogeneity pure enzyme accepts as substrate thiophene acetyl-CoA but it did not 2-hydroxyphenyl and 4-hydroxyphenylacetyl-CoA. The presence of an oxygen atom between the aromatic and the acetyl moieties did not affect the catalysis.     

Production of specific retinal S antigen antibodies in patients with retinal detachment

One hundred patients with retinal detachment (61 primary operations and 39 reoperations) were studied for titers of autoantibodies to human retinal S antigen using the enzyme-linked immunosorbent assay technique (ELISA). There was no statistically significant difference when comparing the group of patients with primary retinal detachment with the control group. However, a statistically significant increase in anti-S titers was recorded when a comparison was made between the group of reoperated patients and the control group (²,P < 0.001) and between the group of reoperated subjects and the group of patients operated on for the first time (²,P < 0.005).Presented at the XVth Meeting of the Club Jules Gonin, Copenhagen, 10–15 August 1986