Liberation of PGF2 alpha from whole blood as an assay to detect inflammatory mediators.
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Animals↗
Biomedical subjects
H Kindahl
Publications and source records attributed to H Kindahl.
Effect of intracervical administration of a prostaglandin E2 gel in pregnant and non-pregnant heifers.
The effects of prostaglandin E2 (PGE2) on cervical opening in non-pregnant and pregnant heifers was studied, and in the pregnant animals the effect on the embryo was studied by means of ultrasonography. In four consecutive experiments, 5 ml of saline, a gel containing 2 mg or 6 mg PGE2 was administered intracervically to four non-pregnant heifers, and 2 mg of PGE2 was administered to heifers pregnant 33 to 40 days. All the groups treated with PGE2 experienced an increase in the concentrations of prostaglandin metabolite in plasma (P < 0.05) shortly after administration, which reached a peak 15 to 30 minutes after administration. An increase in cervical opening was evident in all the PGE2-treated heifers (P < 0.05) from three hours after treatment. There was no difference between the effect of the two doses. The heifers which received saline did not show any significant changes. In addition, the treated heifers showed cervical softening, congestion and mucus secretion which were more pronounced in the pregnant heifers. The embryos were not affected. Plasma progesterone concentrations remained unchanged in all the experiments.
Absorption↗
Alterations in testicular function after endotoxin injection in the boar.
Twelve mature boars were injected intravenously with endotoxin from Salmonella typhimurium. Blood plasma was analysed for 15-ketodihydro-PGF2 alpha, LH and testosterone. The boars were castrated at various times after endotoxin administration and the testes examined by light and electron microscopy. The levels of 15-ketodihydro-PGF2 alpha and LH rose immediately after endotoxin injection followed by an increase in testosterone levels, and in five boars a second increase in LH levels was observed. Morphological examination of the testes revealed infiltration of polymorphonuclear neutrophils (PMN) into the testicular interstitium. The Leydig and myoid cells showed morphological changes. Alterations were also present in the seminiferous epithelium among Sertoli cells, spermatocytes and spermatids. The results indicate that endotoxins can exert a negative effect on testicular function in the boar. Except for the initial increase in LH levels, which is not clearly understood, the hormonal changes are thought to be mediated by alterations in Leydig cell function. The alterations further support previous findings in the boar, and indicate that there is short-term, moderate damage to the seminiferous epithelium following endotoxin injection.
Animals↗
Effects of oral and intravenous administration of endotoxin in prepubertal gilts.
The effect of oral intake of endotoxins was studied in 12 prepubertal gilts. The animals were given 30 or 100 mg of ET each in their regular morning feed ration. Blood samples were collected periodically during 24 h and the clinical status, including rectal temperature, was recorded at the same time. Hematological and clinical chemical analyses that included serum bile acids, glutamate dehydrogenase, alkaline phosphatase, calcium, iron, zinc and a blood plasma metabolite of prostaglandin F2 alpha, were done. The animals showed no obvious clinical symptoms following endotoxin feeding. The major findings were increased bile acid and glutamate dehydrogenase values with the most prominent rises being recorded 10-12 h after endotoxin intake. In a later experiment, 6 animals were injected i.v. with endotoxin in doses in the range 0.1-0.5 micrograms/kg b.w. Blood samples were taken and analysed as in the endotoxin-feeding experiment. Within 1 h of injection, all animals showed symptoms such as vomiting, fever and dyspnea. The clinical signs disappeared within 2-5 h. The injections were followed by increases in bile acids, glutamate dehydrogenase and prostaglandin F2 alpha metabolite. To conclude, this study indicates that clinically healthy prepubertal gilts react to ingested endotoxin in feed but that no apparent clinical disturbances ensue.
Animal Feed↗
Reduced response to intravenous endotoxin injections following repeated oral administration of endotoxin in the pig.
Three prepubertal gilts were each given 100 mg of endotoxin (ET) in their ordinary feed rations, twice daily for 6 days; 3 other gilts received standard feed. Following ET feeding, all animals were injected intravenously (i.v.) with ET (1.0 microgram/kg b.w.) once daily for 5 days. Blood samples were collected and analysed for hematology and total serum bile acids (S-BA), glutamate dehydrogenase (S-GLDH), calcium (S-Ca), iron (S-Fe), zinc (S-Zn) and a blood plasma metabolite (15-ketodihydro-PGF2a; P-PG) of prostaglandin F2a. The animals showed no apparent clinical symptoms following ET-feeding, neither did the blood analyses reveal effects of oral ET. However, when iv ET injections were given, the ET-fed animals showed fewer clinical signs of endotoxemia following the 2nd to 5th injection. S-BA and S-GLDH increased markedly in the standard-fed group following the first injection, while the ET-fed animals showed a much smaller increase in S-BA and no change in S-GLDH on that day. The difference in response may be explained by a direct uptake of ET from the gastrointestinal tract in the ET-fed pigs, making them less sensitive to the injected ET.
Administration, Oral↗
[Uterine motility of cattle during late pregnancy, labor and puerperium. III. Use of flunixin meglumine and endocrine changes].
In the present study the effect of Flunixin meglumine (FM), a cyclooxygenase inhibitor, was investigated on postpartal prostaglandin production and uterine activity in the cow. For that purpose 8 cows were given FM in a dose of 2.2 mg/Kg b.w. twice daily (08.00 and 16.00 h) for the first 10 days p.p. Blood samples were collected at various times before, during and after parturition and the concentrations of 15-keto-13,14-dihydro-PGF2 alpha (PGFM), progesterone as well as adrenaline and noradrenaline determined. Eight cows served as controls. Uterine activity was measured by means of pressure microsensors and electrodes which were surgically implanted into the uterine wall before parturition. During the whole treatment period FM inhibited endogenous PG-production by more than 80% (p < 0.05). The suppressive effect of FM was maximal 4 h after the last injection and lasted no longer than 8 h. PGF2 alpha-suppression clearly decreased spontaneous uterine motility and reduced the myometrial response to ocytocin (5 IU i.v.) and PGF2 alpha (15 mg i.v.). Treatment with FM did not interfere with uterine involution, the return to cyclicity and the first postpartal cycle length. Also, no obvious effects were seen on catecholamine concentrations which fluctuated during parturition without regularly representing the actual stress situation. Our results demonstrate that FM is able to effectively inhibit PGF2 alpha-secretion as well as uterine activity in the cow. Further evaluation of FM as a tocolyticum or in the treatment of uterine infections is required.
Animals↗
Intraluminal pressure variations in the isthmus of the porcine oviduct after intrauterine insemination with saline, oestrogen solution or boar seminal plasma.
The purpose of this study was to investigate if an intrauterine deposition of saline, boar seminal plasma, or an oestrogen solution containing 11.5 micrograms oestrogens affected the intraluminal pressure in the isthmus of the oviduct in unrestrained gilts. In order to monitor variations in intraluminal pressure, 2 ultra-miniature pressure sensors, located at 2 different points along the same isthmus were used. After an initial recording period, either saline, boar seminal plasma, or the oestrogen solution was deposited directly into the uterus. Intraluminal pressure recordings were conducted up to 6 h after insemination, and blood samples, for monitoring oestradiol-17 beta and 15-ketodihydroprostaglandin F2 alpha levels, were collected. None of the inseminates had any consistent effect on the intraluminal pressure in the porcine oviduct. After deposition of the oestrogen solution, increases in the circulating levels of both oestradiol-17 beta and 15-ketodihydroprostaglandin F2 alpha were seen.
Animals↗
A study on the effects of inhibition of prostaglandin biosynthesis with flunixin meglumine and later administration of prostaglandin F2 alpha on the intraluminal pressure variations in the isthmus of the oviduct in unrestrained gilts.
Three gilts were each equipped with 2 ultra-miniature pressure sensors, placed at 2 different points along the same isthmus of the oviduct. Following base recordings of isthmic intraluminal pressure, the gilts were treated with 2.2 mg flunixin meglumine (FM) per kg body weight. After FM treatment, the peripheral plasma levels of 15-ketodihydro-PGF2 alpha, the major metabolite of prostaglandin F2 alpha (PGF2 alpha), decreased within 30 min. The frequency of the phasic pressure fluctuations in the isthmus of the oviduct decreased after FM treatment. Exogenous administration of PGF2 alpha increased the peripheral plasma levels of 15-ketodihydro-PGF2 alpha. When administered at a dose of 0.1 mg, PGF2 alpha produced an increase in the frequency of the phasic pressure fluctuations in the oviductal isthmus. When the PGF2 alpha dose was increased to 0.5 mg, a marked increase in the base and total pressures was seen in addition to the increase in the frequency of the phasic pressure fluctuations.
Animals↗
A possible role of endotoxins in spontaneous paretic cows around parturition.
Six late pregnant old cows which had a history of parturient paresis were studied with respect to clinical and blood biochemical changes during two weeks before and after parturition. The levels of serum endotoxin were evaluated during two days before and after parturition. Three out of six animals showed signs of paresis and two animals needed treatment. The clinical and general changes of all parameters supported the idea that during parturient paresis and parturition, there is absorption of endotoxins from the gastro-intestinal tract. Most of the studied parameters changed similarly to what has been described in experimentally induced endotoxaemia. The animals showed signs of ruminal stasis, had an increase in body temperature, prostaglandin metabolite and endotoxin as well as a decrease in serum calcium, zinc, iron and bile acids levels. The changes of these parameters were also closely related to each other. Furthermore, the changes were more pronounced in paretic cows. Endotoxins absorbed from the gastro-intestinal tract can be involved in paresis and make the outcome of this disease more severe.
Animals↗
Stimulation of vasopressin release in women with primary dysmenorrhoea and after oral contraceptive treatment--effect on uterine contractility.
OBJECTIVE: To study aspects of the aetiology of primary dysmenorrhoea and mechanisms underlying the therapeutic effect in this condition of an oral contraceptive. INTERVENTION: Intrauterine pressure was recorded before and during infusion of hypertonic saline (5% NaCl, 0.06 ml/kg/min) over 75 min on the first day of bleeding in women with dysmenorrhoea and after 3 weeks of oral contraceptive treatment. Plasma sampling every 15 min of ongoing infusion for the estimation of osmolality, arginine vasopressin, oxytocin and the prostaglandin (PG) F-metabolite, 15-keto-13,14-dihydro-PGF2 alpha. SUBJECTS: Ten healthy nulliparous women with moderate to severe primary dysmenorrhoea. MAIN OUTCOME MEASURES: Plasma levels of posterior pituitary hormones and the PGF-metabolite. Total pressure area (TPA) of the recording curve. RESULTS: In dysmenorrhoea before infusion the plasma concentration of vasopressin was in mean 2.18, oxytocin 5.05 and the PGF-metabolite 321.5 pmol/l, and the TPA 3.8 kPa x 10 min. After oral contraceptive treatment the vasopressin level and the TPA were significantly reduced. At both sessions apart from intensifying the pain, the saline infusion increased vasopressin and oxytocin levels as well as the TPA, whereas the concentration of the PGF-metabolite at both sessions decreased. CONCLUSION: Confirmation is provided of the elevated secretion of arginine vasopressin and PGF2 alpha, as well as increased uterine activity in primary dysmenorrhoea. The observations are in agreement with the concept that a lowered level of vasopressin and a decreased uterine activity contributes to the beneficial effect of OCs in the condition. Stimulation of the secretion of vasopressin increases the uterine activity and symptoms of primary dysmenorrhoea, but results suggest that this effect does not involve a mechanism of increased PGF-synthesis. The role of oxytocin in dysmenorrhoea can not yet be defined.
Adult↗
Effect of flunixin meglumine on the endocrine control of luteolysis in the porcine estrous cycle.
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Animals↗
Hormonal interrelationships in postpartum suckled dairy cows.
Three cross-bred cows calved in March and April and were followed until day 62 after parturition. Each animal was suckled by 2 calves ad libitum. All calves were removed from the cows on day 55 after parturition. Blood was collected 3 times per day from the jugular vein by venipuncture. On 4 occasions after parturition--i.e. days 7-8, 21-22, 35-36 and 49-50, the cows were bled through a jugular venous catheter every 30 min during the 24 h. The plasma samples were analyzed for the content of 15-keto-13,14-dihydro-PGF2 alpha (main PGF2 alpha metabolite), LH, prolactin, cortisol and progesterone by radioimmunoassay methods. The concentration of PGF2 alpha increased from 280 to 730 pmol/l within the last 4 days before parturition. The highest geometric mean was 3106 pmol/l on the day of parturition. Thereafter a steady decrease of PGF2 alpha metabolite concentration was seen until day 21 when it reached plateau at 148 pmol/l. In all cows plasma LH concentrations increased significantly (P < 0.05) from about 1.6 micrograms/l on days 7-8 to 2.4 micrograms/l on days 21-22 post partum. The frequency of LH pulses showed no tendency to increase as the postpartum period progressed and averaged 6.5 pulses/24 h. Mean plasma LH concentrations increased from 2.1 micrograms/l 2 days before weaning to 3.2 micrograms/l 2 days after weaning (P < 0.05). LH peaks occurred less frequently in association with prolactin and cortisol peaks than in their absence. A partial positive correlation between PGF2 alpha metabolite and cortisol (r = 0.30) was found on days 7-8 post partum. Correlation between prolactin and cortisol on days 7-8 and 21-22 post partum was also positive (r = 0.20 and r = 0.27, respectively). There was a negative correlation between LH and cortisol on days 7-8 (r = -0.27) and days 49-50 (r = -0.21) post partum. The first and short progesterone increase observed after weaning was terminated in conjunction with PGF2 alpha metabolite peaks.
Animals↗
The role of endotoxins in induced ruminal acidosis in calves.
Experimentally induced ruminal acidosis was carried out in 4 calves to investigate the possibility of resorption of endotoxins from Gram negative bacteria originating from the gastro-intestinal tract. The ruminal acidosis was induced by overfeeding of oats and the effect was evaluated by clinical and blood biochemical changes. Blood samples were collected every 2 h for 60 h before and after experimental feeding. The animals showed signs of ruminal acidosis and also the clinical and blood biochemical changes were similar to those seen after experimental endotoxaemia. However, although being less dramatic the changes in many relevant parameters such as an increase in prostaglandin F metabolite levels, body temperature, endotoxins and a decrease in iron indicate that an endotoxaemic state had occurred. The results of the present study show that ruminal acidosis/stasis is linked to resorption of endotoxins from the gastro-intestinal tract causing endotoxaemia/endotoxicosis.
Acidosis↗
The role of endotoxins in methscopolamine induced ruminal stasis in calves.
Methscopolamine was used to induce ruminal stasis in calves. Clinical and blood biochemical parameters were studied to judge the possible role of gastro-intestinal endotoxins from Gram-negative bacteria. Two trials were carried out where one injection of 100 mg and 3 consecutive injections of 70 mg of methscopolamine were administered. The animals showed signs of ruminal stasis. General clinical signs and changes in blood biochemical parameters were similar to what is found in endotoxaemia or in induced ruminal acidosis. Relevant parameters such as prostaglandin F2 alpha metabolite, endotoxin, iron, zinc, calcium and glutamate dehydrogenase changed significantly indicating exposure of endotoxins.
Animals↗
A technique for continuously monitoring hormone levels in lactating sows and results obtained using it to study LH release.
A technique for collecting continuously blood was successfully applied for the first time in lactating sows. A double-lumen catheter consisted of an internal tubing for delivering an anticoagulant (heparin-saline) and an outer tubing for blood collection. An automatic system, composed of a blood withdrawal pump, an anticoagulant infusion pump and a fraction collector, was connected to the catheter and operated for 12 h on Days 10 and 20 of lactation. Blood samples were collected continuously at a rate of 1 ml per min from four sows. Each fraction consisted of 4 ml blood except during nursing periods when 1 ml blood per fraction was collected. In this study, aliquots of plasma were combined to form pooled 8-min samples for the measurement of the concentrations of LH. Average and base levels of LH, number of LH pulse(s)/12 h and pulse durations were calculated for all pooled samples, all even-numbered samples and all odd-numbered samples. Average and base levels of LH and the number of LH pulses were slightly higher on Day 20 than on Day 10 of lactation. The LH-pulse duration varied between animals, with the value for one of the sows diverging greatly from those of the others. When only every second sample was considered, the LH-pulse rate appeared to be slightly lower.
Animals↗
An oestrogen conjugate enzyme immunoassay for monitoring pregnancy in the mare: limitations of the assay between days 40 and 70 of gestation.
A direct enzyme immunoassay was developed to measure conjugated oestrogens in the plasma of pregnant mares. The antibody was produced in rabbits using oestrone-3-glucuronide (E1G) conjugated to bovine serum albumin. The enzyme conjugate was E1G conjugated to horseradish peroxidase. A sharp increase in plasma E1G concentrations occurred between Days 35 and 40 of gestation. Values declined slightly to Day 45, remained relatively constant to around Day 70 and rose sharply thereafter. Fetal death before Day 35 had no effect on plasma concentrations of E1G. Fetal death after Day 35 in conjunction with endotoxin-induced regression of the corpus luteum (CL) resulted in a decrease in plasma E1G levels to non-pregnant values within 3-4 days. Endotoxaemia without fetal death between Days 35 and 70 resulted in marked, but transient, decreases in plasma E1G concentrations. Fetal death without CL regression after Day 35 did not produce an immediate decline in plasma E1G concentrations and existing levels were maintained for 10-14 days. These findings indicate that between Days 35 and 70 of pregnancy, plasma E1G concentrations are not directly correlated with fetal viability; they appear to reflect increased oestrogen secretion by the CL under the influence of chorionic gonadotropin. After Day 70, E1G concentrations begin to reflect directly the production of oestrogen by the developing feto-placental unit.
Animals↗
Experimental models of endotoxaemia related to abortion in the mare.
Three different routes of administering Salmonella typhimurium endotoxin to mimic naturally occurring endotoxaemia were tried in the mare. Bolus injection, repeated bolus injections and continuous low-dose infusion were compared with prostaglandin F2 alpha release, leucocyte count and clinical response. A biphasic prostaglandin release and a pronounced leucopenia of almost identical patterns were seen in all models. Repeated bolus injections showed that the second injection initiated only a small prostaglandin release indicating the development of refractoriness to the treatment. A similar refractoriness or desensitization occurred during the low-dose infusion. Flunixin meglumine, a potent inhibitor of prostaglandin biosynthesis, administered in different combinations in association with endotoxin demonstrated that this compound must be used at an early stage to prevent endotoxaemia and its deleterious effects on pregnancy. Taken together, the results show that horses are sensitive to endotoxins such that a short period of challenge (about 30 min) is enough to cause clinical signs and reproductive disorders.
Abortion, Veterinary↗
Plasma levels of prostaglandin F2 alpha metabolite and progesterone in repeat breeder heifers.
A detailed clinical-endocrine investigation was performed in 6 repeat breeder heifers (RBH) with the aim being to ascertain whether endocrine asynchronism exists at luteal regression and during early pregnancy. The heifers were first studied during an open cycle and then after insemination when 3 heifers became pregnant. Circulating plasma levels of PGF2 alpha metabolite were measured every 2nd h, while progesterone (P4) levels were measured every 6th h. The oestrous period and intervals between the onset of oestrus and ovulation were relatively longer, compared with what is normally seen in heifers. Plasma levels of P4 at the onset of oestrus were higher than normal, but it was concluded that the plasma levels of PGF2 alpha metabolite and P4 in RBH at luteal regression and early pregnancy were normal.
Animals↗