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Biomedical subjects

J Parantainen

Publications and source records attributed to J Parantainen.

18 recordsLinked to original sources

Catecholamines inhibit leukotriene formation and decrease leukotriene/prostaglandin ratio.

Adrenaline, noradrenaline, isoprenaline, and to a lesser extent dopamine inhibit the release of leukotriene (LT) B2 from calcium ionophore-stimulated human polymorphonuclear leukocytes, while the release of prostaglandin (PG) E2 is proportionally elevated. The inactivity of salbutamol, a noncatechol adrenergic beta 2-receptor agonist, and the inability of propranolol to antagonize the effects of adrenaline, suggest the mediation through beta-receptor independent mechanisms. Neither are alpha-1-receptors involved, as prazosin, a specific antagonist, fails to inhibit the reaction. As the principles for biochemical regulation of LT- and PG-production are met by catecholamines in several tissues, the mechanism is considered to be of general physiological importance. Catecholamines may function as coenzymes/antioxidants which, by altering the redox state of the enzyme iron or heme, decrease the LT/PG ratio thus protecting the organism against tissue anaphylaxis and other LT-related pathophysiology.

Albuterol

A controlled study with taltrimide and sodium valproate: valproate effective in partial epilepsy.

Taltrimide was compared with valproate and placebo in 17 patients with intractable epilepsy being on carbamazepine monotherapy. Taltrimide (400 mg/day), valproate (1000 mg/day) or placebo were added to the treatment for periods of 3 months using a randomized cross-over design. Serum carbamazepine concentrations remained within the therapeutic range throughout the trial. Thirteen patients completed the study. In partial epilepsy of 7 the seizure frequency was reduced by 27% during valproate (p less than 0.05), compared with placebo, while no improvement was found during taltrimide. In 6 with primary generalized epilepsy, the number of seizures was reduced by 49% during taltrimide and by 38% during valproate, but neither effect was significant, compared with placebo. Headache was reported by 3 patients while on taltrimide. One with hypersensitivity history developed petecchiae and nasal bleeding during taltrimide and, therefore, the treatment was stopped. The three other interruptions were independent of taltrimide. Thus, the only statistically significant effect in this study was that of valproate in partial epilepsy.

Adolescent

Inflammation-related changes in cyclic AMP and cyclic GMP in bovine mastitis.

Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) concentrations in milk and plasma samples from healthy and mastitic cows were determined by radioimmunoassay and compared with prostaglandins (PGE2, PGF2 alpha and thromboxane B2 [TXB2]), phospholipids and other relevant parameters in milk and blood. The concentrations of cAMP were about five times higher in plasma (p less than 0.01) than in milk, whereas the cGMP concentration in milk was three times higher (p less than 0.01) than that in plasma in both healthy and diseased animals. In mastitic milk, the cAMP and cGMP concentrations were 19% and 65% and in blood plasma 13% and 84% higher respectively than in healthy animals. In milk, cyclic nucleotide concentrations correlated with the markedly elevated cell count and also with the prostaglandin concentration and pH. In blood, cAMP correlated positively with phospholipids and cGMP with reduced glutathione (GSH). These changes are considered to be important in the disease process and, in particular, the increase in cGMP deserves further study.

Animals

Free fatty acids and lipid peroxidation in normal and mastitic bovine milk.

Milk levels of free fatty acids (FFA) and prostaglandins (PGs) were determined in healthy cows and in those with mastitis and compared with some parameters commonly used for diagnosing mastitis. A modified gas chromatography-mass spectrometry method was used. In mastitis there was a substantial overall increase in FFA levels in milk. Specific attention was paid to the fate of the long-chain polyunsaturated fatty acids, known as precursors for the production of PGs, leukotrienes and other eicosanoids. Both the omega-6 and omega-3 lines of these lipids were increased in mastitis, but only in proportion to other FFA. The milk levels of PGs (PGF2, PGF2 alpha, thromboxane B2) were elevated in the same proportion. The possible importance of lipid peroxidation, inflammatory reaction and host defence are evaluated in relation to tissue destruction and oxidative killing of pathogens. It may be possible to manipulate the intake and fate of FFA in the organism by dietary intake, antioxidants and proper storing of feed. It is concluded that in studies concerning FFA special attention should be given to those long-chain fatty acids that are precursors for the formation of eicosanoids.

Animals

Role of plasma fatty acids, prostaglandins and antioxidant balance in bovine mastitis.

Plasma levels of free fatty acids (FFA) were measured in cows with mastitis. FFA levels are known to be elevated in milk of affected cows, and similar increases were now observed in blood plasma. Of the long-chain polyunsaturated fatty acids which serve as precursors for prostaglandins (PGs), leukotrienes (LT) and related eicosanoids, arachidonic acid (C20: 4 omega-6) was elevated by 156 per cent and C20: 3 (consisting of both omega-3 and omega-6) 153 per cent; eicosapentaenoic acid (20: 5 omega-3), not present in the plasma of healthy animals, was detected in blood of mastitic animals. Arachidonic acid correlated positively with the plasma levels of PGs. Total plasma phospholipids were increased as well, and they were positively correlated with the levels of linoleic and arachidonic acids. Changes in FFA levels correlated positively with parameters of inflammation, like bovine serum albumin and serum N-acetyl-beta-D-glucosaminidase, but negatively with the antioxidant status of the animals (vitamin E, glutathione peroxidase). As PGs and LTs are mediators of inflammation, and products of lipid peroxidation, the increase of plasma FFA could be related to tissue damage caused by oxygen free radicals. Similar processes are, however, involved also in host defence, e.g. in oxidative killing of pathogens.

Acetylglucosaminidase

Evidence for the presence of cytochrome P-450 in mastitic bovine mammary gland.

The content of cytochrome P-450 in mastitic and healthy lactating bovine mammary gland was analyzed. Evidence for the existence of cytochrome P-450 in mastitic tissues was found. The amount of cytochrome P-450 formed in the assay ranged from 0.017 to 0.031 nmole/mg protein. The highest concentrations were found in severely inflamed samples, whereas and traces or no cytochrome P-450 were found in healthy tissues. The significance of cytochrome P-450 in mastitic mammary gland is discussed in relation to host defence involving oxidative killing of pathogens.

Animals

Tolfenamic acid is as effective as ergotamine during migraine attacks.

Tolfenamic acid (a potent inhibitor of prostaglandin biosynthesis), ergotamine tartrate, acetylsalicylic acid, or placebo was administered during 160 migraine attacks in twenty women in a double-blind, cross-over study. Tolfenamic acid and ergotamine were equally effective in reducing the duration and intensity of attacks, but side-effects, especially nausea, were less common with tolfenamic acid. This probably accounted for the patients' preference for tolfenamic acid. The effectiveness of tolfenamic acid in acute migraine attacks accords with the postulated role of prostaglandins in migraine.

Adolescent

Effect of lowering of the temperature on the tissue levels of cAMP, cGMP, PGE and PGF2 alpha in spontaneously beating rat atria preparation.

Tissue levels of cAMP, cGMP, PGE, and PGF2 alpha were measured in spontaneously beating rat atria preparation at 20C and 37C. At 20C the formation of cAMP increased in correlation with the markedly increased amplitude and reduced frequency. The other biochemical parameters were not significantly affected by the low temperature.

Adaptation, Physiological

Prostaglandins; their biological and pharmacological role.

The biological and pharmacological roles of prostaglandin system are reviewed. The most recent and important finding is the isolation and characterization of endoperoxides, thromboxanes and prostacyclin. In many respect they seem to be even more effective than the original prostaglandins and could explain many actions previously attributed to prostaglandins. Prostaglandins, endoperoxides, thromboxanes, and prostacyclin seem to have important physiological and pathophysiological roles, e.g. in the cardiovascular, gastro-intestinal and reproductive systems, the skin, and the central nervous system, as well as in inflammatory, immunological and metabolic reactions. Thus, prostaglandin-like substances, their analogues, prostaglandin antagonists, and the drugs that affect prostaglandin synthesis present good prospects for the treatment of many diseases affecting these systems. The mode of action of most anti-inflammatory and analgesic drugs can be explained by actions on the prostaglandin system. New potent and selective regulators of the prostaglandin system are being investigated and more indications are being found for using existing drugs. Although the field is generally promising, there are many contradictory findings. This calls for a cautious interpretation of the many interesting observations.

Animals

The role of cyclic nucleotides and prostaglandins in heart function.

A short review of the role of cyclic nucleotides and prostaglandins (PGs) in normal and pathological functions of the heart is given. Possible interrelationships of these two regulatory systems have been studied by using spontaneously beating rat atria preparations. Addition of noradrenaline (NA) to the incubate (1 . 10(-6) M) caused an increase in amplitude and frequency which was preceded and parallelled by an elevation of the tissue cAMP level. A transient increase in cGMP and PGE values was also seen. Propranolol (5 . 10(-6) M) abolished the increase in amplitude and frequency as well as in cAMP and PGE concentrations. Indomethacin (1 . 10(-5) M) inhibited the formation of PGE. The increase in cGMP was blocked by phenoxybenzamine. Interchange between beta- and alpha-receptors according as the temperature is lowered has been described earlier. Hypothermia (20 degrees C) had a positive inotropic effect on the atria and increased the tissue cAMP concentration. Loading of the atria caused an increase in cAMP without any effects on cGMP or PGs. Slight hypoxia did not change the cAMP or PG levels, but elevated the cGMP values. Arrhythmias induced by hypo- or hyperpotassemia did not modify the biochemical parameters measured. PGF2alpha (1. 10(-5) M) normalized the atrial rhythm and increased the amplitude without changing cyclic nucleotide or PG levels. PGE1 (1 . 10(-4) M) increased the amplitude of normorhythmic atria and the tissue concentration of cAMP. PGE2 was the only PG tested which stimulated the heart adenylate cyclase in vitro. There seems to be close but complicated relationships between cyclic nucleotides and PGs in the heart.

Adenylyl Cyclases

A sensitive biological assay for prostaglandin E and acetylcholine.

Superfused hamster stomach strip has been used in the bioassay of prostaglandin E2 (PGE2) and acetylcholine. The preparation proved very stable and had no spontaneous movements. The sensitivity to PGE2 (and PGE1) was in the range of 10(-9) g ml(-1) and to acetylcholine 10(-12) g ml(-1). After treatment with physostigmine the sensitivity to acetylcholine was 10(-15) g ml(-1). In acetylcholine determination the preparation is more sensitive than any other method.

Acetylcholine

Inhibition of prostaglandin biosynthesis by tolfenamic acid in vitro.

The effect of tolfenamic acid on prostaglandin biosynthesis was investigated by using rabbit kidney medulla microsomal fraction, and the results compared with those obtained with indomethacin and acetylsalicylic acid. Tolfenamic acid inhibited the conversion of arachidonic acid to prostaglandin E2 very effectively and in a dose-dependent manner. IC50 values were 0.64 muM for tolfenamic acid, 0.76 muM for indomethacin, and 7 mM for acetylsalicylic acid. The inhibition of prostaglandin biosynthesis may be related to the good anti-inflammatory action of tolfenamic acid.

Animals