Controlled Comparison of the Bronchodilator Effects of Three β-Adrenergic Stimulant Drugs Administered by Inhalation to Patients with Asthma

In a double-blind trial of the effect of inhaling three different β-adrenergic stimulants (isoprenaline sulphate 1,000 μg., orciprenaline sulphate 1,500 μg., and salbutamol 200 μg.) and a placebo on ventilatory function in 24 patients with chronic asthma salbutamol was found to have a much longer action than isoprenaline, and it produced a slightly more intense and prolonged effect than orciprenaline. In a double-blind subjective assessment 13 of the 24 patients selected salbutamol as the most effective preparation, while only five preferred isoprenaline and three orciprenaline. Hence salbutamol, given by inhalation, may prove to be the most effective drug at present available for the short-term relief of asthmatic symptoms.     

Antagonistic Action of Aerosols of Prostaglandins F2α and E2 on Bronchial Muscle Tone in Man

Experiments were carried out in healthy male volunteers to investigate the effect of the inhalation of prostaglandin F₂α (PGF₂α) on airways resistance and the influence of the subsequent inhalation of prostaglandin E₂ (PGE₂). Airways resistance, which reflects the tone of smooth muscle in the larger airways in man, was measured by total body plethysmography.The inhalation of PGF₂α (40-60 μg) caused an increase in airways resistance in all subjects. Both PGE₂ (55 μg) and isoprenaline (550 μg) given by metered aerosol promptly reversed the bronchoconstriction induced by PGF₂α, but isoprenaline was more effective in this respect.A role for these prostaglandins in the control of bronchial muscle tone is discussed.     

Response of Asthmatics to Isoprenaline and Salbutamol Aerosols Administered by Intermittent Positive-pressure Ventilation

The bronchodilator and cardiac effects produced by aerosols of 0·5% isoprenaline and of 0·25, 0·5, and 1% salbutamol administered in 40% oxygen by intermittent positive-pressure ventilation were compared in 24 asthmatic patients. Isoprenaline and salbutamol in concentrations of 0·5% were equipotent in peak bronchodilator effect; salbutamol was superior in total bronchodilator effect and duration of average effect, but the peak bronchodilator effect occurred earlier after isoprenaline. Significantly greater tachycardia was produced by 0·5% isoprenaline than by the same concentration of salbutamol. The 0·25, 0·5, and 1% concentrations of salbutamol had about the same peak bronchodilator effect, but there was a stepwise increase in total effect and duration of average effect in relation to the concentration used. A similar stepwise increase in heart rate was also noted, but with all concentrations this was significantly less than with 0·5% isoprenaline. It was concluded that a 0·5% solution of salbutamol, which provided maximal bronchodilatation without important tachycardia, was therapeutically superior to the other three treatments.     

Effects of Salbutamol and Isoprenaline Phenylephrine in Reversible Airways Obstruction

Ventolin (salbutamol) and Medihaler-Duo (isoprenaline/phenylephrine combination) standard pressurized inhalers were used to administer doses of two or six “puffs” to 16 patients with known reversible airways obstruction. The doses were administered in random order over two days. Both the Ventolin and Medihaler-Duo inhalers substantially increased FEV₁, but in the doses used salbutamol was more effective than isoprenaline/phenylephrine (P < 0·01). There was no significant difference between two and six puffs of salbutamol, though there seemed to be an advantage of six puffs of isoprenaline/phenylephrine over two puffs (P < 0·05). Adrenaline (1/1,000) 0·5 ml and atropine 0·6 mg produced similar increases in FEV₁ to those produced by salbutamol.The Pao₂ fell more than 5 mm Hg in three patients after salbutamol and in three after isoprenaline/phenylephrine. There was no significant fall in mean Pao₂ in any of the treatment groups. It is concluded that the Ventolin inhalant, administered in the conventional dose of two puffs, is as effective a bronchodilator as subcutaneous adrenaline and atropine, is more effective than the Medihaler-Duo, and is without detectable side effects.     

Accumulation of Trehalose and Sucrose in Cyanobacteria Exposed to Matric Water Stress

The drought-resistant cyanobacteria Phormidium autumnale, strain LPP₄, and a Chroococcidiopsis sp. accumulated trehalose, sucrose, and both trehalose and sucrose, respectively, in response to matric water stress. Accumulated sugar concentrations reached values of up to 6.2 μg of trehalose per μg of chlorophyll in P. autumnale, 6.9 μg of sucrose per μg of chlorophyll in LPP₄, and 4.1 μg of sucrose and 3.2 μg of trehalose per μg of chlorophyll in the Chroococcidiopsis sp. The same sugars were accumulated by these cyanobacteria in similar concentrations under osmotic water stress. Cyanobacteria that did not show drought resistance (Plectonema boryanum and Synechococcus strain PCC 7942) did not accumulate significant amounts of sugars when matric water stress was applied.     

Evaluation of the Protective and Therapeutic Properties of DBCP for Control of Root-Knot Nematode on Tomato

Twelve soil drenches over a period of 30 days with DBCP concentrations of 40 μg/ml did not completely prevent infection of tomato plants by root-knot nematode juveniles. Repeated DBCP drenches of 40 μg/ml halted gall development during the drenches, but 10 days after drenching was discontinued galls were apparent. DBCP drenches at 200 μg/ml prevented tomato root development, and 40 μg/ml slowed it. Ten μg/ml increased the height of root-knot-infected plants, but not their top weights. Treated plants were lanky. Protective drenches of 2.5 to 40 μg/ml of DBCP decreased nematode populations and increased fruitfulness. DBCP as a therapeutant reduced the incidence of galling on new roots and halted increases in gall size on previously infected roots but did not improve fruitfulness or plant size significantly.     

Effect of Salbutamol on Spirometry and Blood-gas Tensions in Bronchial Asthma

A new bronchodilator drug, salbutamol, reduced airway obstruction in 37 patients with bronchial asthma but did not lead to a significant fall in lowered arterial oxygen tension. This drug, unlike other bronchodilators, appears to have little or no effect on the cardiovascular system, and it is suggested that it does not therefore lead to an intensification of the ventilation/perfusion disturbance in the lung leading to a worsening of hypoxaemia.     

Growth of Potato and Control of Pratylenchus penetrans with Oxamyl-treated Seed Pieces in Greenhouse Studies

Oxamyl was applied to both uncut and cut potato tubers in aqueous solutions of 1,000 to 32,000 μg/ml. Emergence in greenhouse pots was delayed for a day or more after soaking cut tuber pieces in 32,000 μg/ml. After 10 weeks plant growth was greater, relative to the control, when Pratylenchus penetrans-infested soil was planted with cut tubers soaked for 20 minutes in 32,000 μg/ml. Soaking for 40 minutes did not increase nematode control nor affect plant growth. Oxamyl applied to tubers at 1,000 μg/ml reduced the numbers of P. penetrans in the soil by 20% and in the roots by 35%; at 32,000 μg/ml, the numbers of P. penetrans in the soil were reduced by 73-86% and in the roots by 86-97%. The numbers of P. penetrans did not increase in the roots of plants developed from cut tubers soaked in 32,000 μg/ml over a period of 10 weeks, but numbers of lesion nematodes had begun to increase in the soil.     

Effect of Vancomycin on the Growth of Psittacosis-Trachoma Agents Cultivated in Eggs and Cell Culture

The antibiotic vancomycin was effective in preventing bacterial contamination during studies with psittacosis and trachoma (PT) agents. This antibiotic was not toxic to chick embryos at 80 mg per egg, or to HeLa 229 cells cultivated in a medium containing 3,200 μg/ml of vancomycin; however, it was toxic to LLC-MK2 cells at a concentration of 1,600 μg/ml. Vancomycin did not affect the growth of a variety of PT agents at a concentration of 2 mg per egg or 800 μg per ml of cell culture medium, but it did inhibit the growth of common gram-positive bacterial air contaminants.     

Effect on airways resistance of prostaglandin E1 given by aerosol to healthy and asthmatic volunteers

The forced expiratory volume in one second (F.E.V.₁) was measured in healthy and asthmatic volunteers and the inhalation of prostaglandin E₁ (PGE₁) was compared with that of isoprenaline, using metered aerosols.In healthy volunteers PGE₁, either as the free acid or the neutral triethanolamine salt, did not affect the F.E.V.₁; the free acid was irritant to the upper respiratory tract. In five out of six asthmatic volunteers with reversible airways obstruction, inhalation of 55 μg of PGE₁ (triethanolamine salt) produced an increase in F.E.V.₁ comparable in both degree and duration to that produced by an inhalation of 550 μg. of isoprenaline sulphate.Though the triethanolamine salt was well tolerated in most of the asthmatic subjects studied, in one asthmatic subject this preparation caused coughing and there was a progressive reduction in the F.E.V.₁ associated with bronchospasm.     

Mode of Action of Lomofungin

Lomofungin inhibited the growth of some yeasts and mycelial fungi at concentrations between 5 and 10 μg/ml. At such concentrations, there was no decrease in endogenous and exogenous oxygen consumption, and even 50 μg of antibiotic per ml caused only slight decreases. The permeation of the cell membrane was changed so that leakage of ninhydrin-positive substances was reduced, and the uptake of ¹⁴C-labeled glucose, amino acids, uracil, and thymidine was decreased at concentrations as low as 4 μg/ml. Protein synthesis in whole cells of Saccharomyces cerevisiae was reduced 35% at 10 μg/ml. However, the antibiotic did not reduce the incorporation of phenylalanine-U-¹⁴C into polypeptides with cell-free systems of Rhizoctonia solani and S. cerevisiae. The synthesis of ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) was inhibited even at concentrations of lomofungin of 4 μg/ml. Since RNA synthesis was inhibited at lower concentrations and earlier than DNA synthesis, the primary site of action of the antibiotic appears to be the synthesis of RNA.     

Mode of Action of Lomofungin

Lomofungin inhibited the growth of some yeasts and mycelial fungi at concentrations between 5 and 10 μg/ml. At such concentrations, there was no decrease in endogenous and exogenous oxygen consumption, and even 50 μg of antibiotic per ml caused only slight decreases. The permeation of the cell membrane was changed so that leakage of ninhydrin-positive substances was reduced, and the uptake of ¹⁴C-labeled glucose, amino acids, uracil, and thymidine was decreased at concentrations as low as 4 μg/ml. Protein synthesis in whole cells of Saccharomyces cerevisiae was reduced 35% at 10 μg/ml. However, the antibiotic did not reduce the incorporation of phenylalanine-U-¹⁴C into polypeptides with cell-free systems of Rhizoctonia solani and S. cerevisiae. The synthesis of ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) was inhibited even at concentrations of lomofungin of 4 μg/ml. Since RNA synthesis was inhibited at lower concentrations and earlier than DNA synthesis, the primary site of action of the antibiotic appears to be the synthesis of RNA.     

Tolerance to bronchodilation during treatment with long-acting beta-agonists,a randomised controlled trial

Background

Regular use of beta-agonists leads to tolerance to their bronchodilator effects. This can be demonstrated by measuring the response to beta-agonist following bronchoconstriction using methacholine. However most studies have demonstrated tolerance after a period of beta-agonist withdrawal, which is not typical of their use in clinical practice. This study assessed tolerance to the bronchodilator action of salbutamol during ongoing treatment with long-acting beta-agonist.

Methods

Random-order, double-blind, placebo-controlled, crossover trial. After 1 week without beta-agonists, 13 asthmatic subjects inhaled formoterol 12 μg twice daily or matching placebo for 1 week. Eight hours after the first and last doses subjects inhaled methacholine to produce a 20% fall in FEV₁. Salbutamol 100, 200 and 400 μg (cumulative dose) was then given at 5-minute intervals and FEV₁ was measured 5 minutes after each dose. After a 1 week washout subjects crossed over to the other treatment. Unscheduled use of beta-agonists was not allowed during the study. The main outcome variable was the area under the salbutamol response curve.

Results

The analysis showed a significant time by treatment interaction indicating that the response to salbutamol fell during formoterol therapy compared to placebo. After 1 week of formoterol the area under the salbutamol response curve was 48% (95% confidence interval 28 to 68%) lower than placebo. This reduction in response remained significant when the analyses were adjusted for changes in the pre-challenge FEV₁ and dose of methacholine given (p = 0.001).

Conclusion

The bronchodilator response to salbutamol is significantly reduced in patients taking formoterol. Clinically relevant tolerance to rescue beta-agonist treatment is likely to occur in patients treated with long-acting beta-agonists.     

The interference of ozone gas in kinects and mitochondrial potential of equine sperm submitted on cryopreservation

The objective of this study was to evaluate the effects of the addition of different concentrations of ozone to quarter horse semen submitted to cryopreservation. Six ejaculates from four stallions were collected and were divided in four experimental groups: a control group (BotuCRIO® extender) and three other groups with BotuCRIO® ozonized at concentrations of 6, 8 and 12 μg of O₃/mL. The semen samples were diluted (200 x 10⁶ spermatozoa/mL), filled in straws and frozen. After thawing (37 ºC, 30s), the samples were evaluated at 0, 30 and 60 minutes of incubation regarding sperm kinetics by a computer-assisted sperm analysis (CASA), and plasma membrane integrity (PMI), acrosome integrity (ACi) and mitochondrial membrane potential (MMP) by fluorescent probes. There was a reduction in the kinetic parameters total motility (TM), progressive motility (PM), curvilinear velocity (VCL), straight line velocity (VSL) and average path velocity (VAP) in all groups during the thermoresistance test (TT), a pattern also found in PMI and MMP analyses (p<0.05). There was no difference (p>0.05) between the control and treatment (6, 8, and 12 μg of O₃/mL) groups, in any of the evaluated times for the kinetic parameters TM, linearity (LIN), straightness (STR), wobble index (WOB), amplitude of lateral head displacement (ALH) and beat cross frequency (BCF). Regarding the VCL, VSL and VAP parameters, the group treated with 6 μg did not differ from the control or from 8 μg, but was higher than 12 μg at 30 and 60 minutes. ACi and PMI did not differ between groups (p>0.05), but PMI was lower in groups 8 μg and 12 μg compared to the control and 6 μg (p<0.05). It was concluded that the addition of ozone does not present beneficial effects for cryopreservation of equine semen at the concentrations used and decreases important parameters of fertility.     

Decline in Deoxynivalenol (Vomitoxin) Concentrations in 1983 Ontario Winter Wheat Before Harvest

Samples of winter wheat were collected in 1983 from five fields in southwestern Ontario that were naturally infected with head blight. The geometric mean concentration of deoxynivalenol (vomitoxin) in the grain declined significantly from 1.56 μg/g on 7 July to 0.21 μg/g on 14 July and 0.11 μg/g on 18 July and did not increase at harvest (20 through 27 July).     

In Vitro Hatch and Survival of Heterodera glycines as Affected by Alachlor and Phenamiphos

Heterodera glycines (race 1) eggs were exposed to aqueous solutions o f selected concentrations o f the herbicide alachlor and the organophosphate nematicide phenamiphos alone and in herbicide-nematicide combinations. Phenamiphos (0.5 μg/ml) + alachlor (0.063, 0.125, or 1.0 μg/ ml) treatments increased the incidence o f juvenile hatch over that of untreated controls at 18 days. At 18 and 25 days, phenamiphos (0.5 μg/ml) treatments contained more juveniles than did phenamiphos at 1.0 μg/ml. Phenamiphos (1.0 μg/ml) alone and in combination with alachlor (1.0 μg/ ml) suppressed hatch for 21 days and juvenile survival for more than 21 days. Alachlor treatments enhanced juvenile survival compared to the untreated control at 14 and 21 days. Technical alachlor gave results similar to those of the formulated product.     

Resistance of Pseudomonas aeruginosa to gentamicin

The resistance to gentamicin 4 μg./ml. of 250 Pseudomonas aeruginosa isolates was measured by a proportion method. Twenty-eight (11.2%) of the cultures fell into the most resistant group, in whose populations between 10 and 100% of the organisms were resistant. A relatively high percentage of urinary isolates and a comparatively low percentage of isolates from respiratory sources occurred in this group. Three of the 28 were resistant to carbenicillin 150 μg./ml. and 6 of 18 tested were as resistant to gentamicin 8 μg./ml. as they were to 4 μg./ml. The distribution of Ps. aeruginosa isolates between the different grades of resistance did not change significantly during the 10 months in which the survey was performed.     

Long-Term Responses to Loss of Renal Mass: Pathophysiological Aspects: Role of Solute Excretion in Prevention of Norepinephrine-Induced Acute Renal Failure

Infusion of 0.75 μ g/kgbw/min norepinephrine (NE), for 40 minutes, into one renal artery in anesthetized dogs, induced acute renal failure (ARF). Subsequently there was nearly complete reversal of function within 8 weeks. Isotonic saline volume expansion, or renal vasodilation plus diuresis by acetylcholine (into renal artery: 20 μg/min) did not protect against this type of ARF. Volume expansion with either 5 or 20 percent mannitol partly prevented the fall of GFR 3 hours after NE, this protection being correlated with the magnitude of the osmolar clearance at the time of the insult. IV furosemide (10 mg/kg + 10 mg/kg/h; fluid losses replaced) afforded an even better protection. Proximal tubular necrosis in the “protected” kidneys was as severe as in non-protected kidneys. Glomerular cell morphology (scanning electron microscopy) was not altered by the 40-minute NE infusions. Functional “protection” appeared to depend on solute diuresis at the time of insult.     

Concentrations of glycerides and phospholipids in rat heart and gastrocnemius muscles: Effects of alloxan-diabetes and perfusion

1. Methods are described for the extraction of lipid and assay of mono-, di- and tri-glyceride glycerol and phospholipid phosphorus in rat heart and gastrocnemius muscles. 2. In hearts from normal animals, concentrations found were: monoglyceride, 0·6; diglyceride, 0·1; triglyceride, 12·6μmoles of glyceride glycerol/g. of dry muscle; phospholipid, 171μg.atoms of phospholipid phosphorus/g. of dry muscle. Concentrations of glycerides in gastrocnemius muscle were similar to heart muscle but those of phospholipids were lower (64μg.atoms of phospholipid phosphorus/g. of dry muscle). 3. Alloxan-diabetes increased the concentration of triglyceride in the muscles twofold. This increase was shown to be dependent in the heart on the availability of growth hormone and cortisol but not on the availability of dietary lipid. Total glyceride in the heart was increased after 48 and 72hr. starvation but not after 96hr. Changes in glyceride concentration seen in starvation and diabetes were not associated with significant changes in phospholipid concentration. It is suggested that mobilization of free fatty acids in diabetes leads to the synthesis of additional glyceride in muscle. 4. The possible contribution of glyceride fatty acid in the heart to respiration during perfusion has been calculated from the net loss of glyceride during perfusion, and also from the relative rates of lipolysis and esterification and compared with oxidation of fatty acid required for the balance of oxygen consumption (oxygen not utilized in the oxidation of glucose or glycogen glucose). In the normal or diabetic heart perfused with glucose and insulin the breakdown of glyceride can account for the balance of oxygen consumption. In the normal heart perfused without substrate the balance of oxygen consumption is not entirely accounted for by the breakdown of glyceride.     

Production of Beauvericin, Moniliformin, Fusaproliferin, and Fumonisins B1, B2, and B3 by Fifteen Ex-Type Strains of Fusarium Species

Fifteen Fusarium species were analyzed by high-performance liquid chromatography for the production of six mycotoxins in corn grits cultures. Production of mycotoxins ranged from 66 to 2,500 μg/kg for fumonisin B₁, 0.6 to 1,500 μg/g for moniliformin, 2.2 to 720 μg/g for beauvericin, and 12 to 130 μg/g for fusaproliferin. Fumonisin B₂ (360 μg/kg) was produced by two species, fumonisin B₃ was not detected in any of the 15 species examined, and Fusarium bulbicola produced none of the six mycotoxins that we analyzed.