Enhancement of anaphylactic mediator release from guinea-pig perfused lungs by fatty acid hydroperoxides

Fragments of chopped lung from indomethacin treated guinea-pigs had an anti-aggregating effect when added to human platelet rich plasma (PRP), probably due to the production of prostacyclin (PGI₂) since the effect was inhibited by 15-hydroperoxy arachidonic acid (15-HPAA, 10 μg ml^?1). Both 15-HPAA (1–20 μg ml^?1 min^?1) and 13-hydroperoxy linoleic acid (13-HPLA, 20 μg ml^?1 min^?1) caused a marked enhancement of the anaphylactic release of histamine, slow-reacting substance of anaphylaxis (SRS-A) and rabbit aorta contracting substance (RCS) from guinea-pig isolated perfused lungs. This enhancement was not reversed by the concomitant infusion of either PGI₂ (5 μg ml^?1 min^?1) or 6-oxo-prostaglandin F_1α (6-oxo-PGF_1α, 5 μg ml^?1 min^?1). Anaphylactic release of histamine and SRS-A from guinea-pig perfused lungs was not inhibited by PGI₂ (10 ng - 10 μg ml^?1 min^?1) but was inhibited by PGE₂ (5 and 10 μg ml^?1 min^?1). Antiserum raised to 5,6-dihydro prostacyclin (PGI₁) in rabbits, which also binds PGI₂, had no effect on the release of anaphylactic mediators. The fatty acid hydroperoxides may enhance mediator release either indirectly by augmenting thromboxane production or by a direct effect on sensitized cells. Further experiments to distinguish between these alternatives are described in the accompanying paper (27).     

Dose-dependent inhibitory and non-inhibitory action of somatostatin on insulin release in rats

The dose-dependent effect of intravenously infused synthetic somatostatin-14 on basal and postprandial insulin and gastrin release was assessed in anesthetized rats.Infusion of 1 ng · kg^?1 · min^?1 elicited a significant reduction of basal and postprandial insulin levels compared to the saline control group. At 15 ng · kg^?1 · min^?1 basal insulin was not affected but postprandial insulin levels were still significantly reduced. At 30 ng · kg^?1 · min^?1 neither basal nor stimulated insulin levels were affected. At the highest concentration of 120 ng · kg^?1 · min^?1 basal and postprandial insulin levels were suppressed similar to the lowest infusion rate of 1 ng · kg^?1 · min^?1. Basal gastrin levels were significantly reduced only at the highest rate of 120 ng · kg^?1 · min^?1. A significant reduction of postprandial gastrin levels was observed at 15 ng · kg^?1 · min^?1 and all higher infusion rates employed. Measurements of plasma somatostatin-like immunoreactivity (SLI) demonstrated that plasma SLI levels during the lowest infusion rate of 1 ng · kg^?1 · min^?1 were not different from the controls. No significant rise of plasma SLI levels was observed in response to the test meal. The higher infusion rates elicited a dose-dependent increase in plasma SLI levels. These data demonstrate that in rats somatostatin exerts a biological effect on insulin release at very low doses while certain greater infusion rates have no suppressive effect. Gastrin secretion is inhibited in a more linear pattern.     

Measurement of 6-oxo-PGF1α in human plasma using gas chromatography-mass spectrometry

The plasma concentration of the prostacyclin (PGI₂) hydration product 6-oxo-PGF_1α has been assayed by stable isotope dilution GC-MS in six normal volunteers infused with increasing doses of PGI₂ intravenously. The predosing levels of 6-oxo-PGF_1α ranged between 114 and 266 pg/ml. Infusion of PGI₂ increased 6-oxo-PGF_1α concentration in plasma but the increments were lower than expected suggesting less conversion of the PGI₂ to 6-oxo-PGF_1α at high infusion rates.     

The mechanism of enhancement by fatty acid hydroperoxides of anaphylactic mediator release

Fragments of chopped lung from indomethacin treated guinea-pigs had an anti-aggregating effect when added to human platelet rich plasma (PRP), probably due to the production of prostacyclin (PGI₂) since the effect was inhibited by 15-hydroperoxy arachidonic acid (15-HPAA, 10 μg ml⁻¹). Both 15-HPAA (1–20 μg ml⁻¹ min⁻¹) and 13-hydroperoxy linoleic acid (13-HPLA, 20 μg ml⁻¹ min⁻¹) caused a marked enhancement of the anaphylactic release of histamine, slow-reacting substance of anaphylaxis (SRS-A) and rabbit aorta contracting substance (RCS) from guinea-pig isolated perfused lungs. This enhancement was not reversed by the concomitant infusion of either PGI₂ (5 μg ml⁻¹ min⁻¹) or 6-oxo-prostaglandin F_1α (6-oxo-PGF_1α, 5 μg ml⁻¹ min⁻¹). Anaphylactic release of histamine and SRS-A from guinea-pig perfused lungs was not inhibited by PGI₂ (10 ng - 10 μg ml⁻¹ min⁻¹) but was inhibited by PGE₂ (5 and 10 μg ml⁻¹ min⁻¹). Antiserum raised to 5,6-dihydro prostacyclin (PGI₁) in rabbits, which also binds PGI₂, had no effect on the release of anaphylactic mediators. The fatty acid hydroperoxides may enhance mediator release either indirectly by augmenting thromboxane production or by a direct effect on sensitized cells. Further experiments to distinguish between these alternatives are described in the accompanying paper (27).     

Prostaglandins in rainbow trout (Oncorhynchus mykiss Walbaum, 1792) sperm biology – searching for answers

The purpose of this study was to determine the concentrations of prostaglandins E₂ and F_2α (PGE₂ and PGF_2α) in the blood, testis and seminal plasma of mature male rainbow trout and in the ovarian fluid to assess the effects of these prostaglandins on sperm motility parameters when present in activation media. Also prolonged incubation with prostaglandins on sperm motility and calcium influx were studied. The profile of PGE₂ and PGF_2α differed in concentration between blood, testicular supernatant and seminal plasma. PGE₂ was predominant in the blood sample (0.29 ng ml^?1) and testicular supernatant (3.1 ng ml^?1) whereas their level in seminal plasma was lower than PGF_2α (0.23 ng ml^?1). The concentrations of PGF_2α in blood, testis and seminal plasma were 0.04, 0.99, 1.3 ng ml^?1, respectively. In the ovarian fluid the concentrations of both prostaglandins were higher than in the male reproductive tract. Adding both prostaglandins to activation buffer (at concentrations 15 and 70 ng ml^?1) had no effect on any CASA parameters. Calcium influx related to rainbow trout sperm incubations with PGE₂, and PGF_2α was not detected. After 24 h incubation of sperm in artificial seminal plasma solution without and with prostaglandins all sperm samples increased their motility potential and intracellular calcium concentration. Therefore, this effect was not related to the presence of prostaglandins. In summary PGE₂, and PGF_2α were present in the rainbow trout male reproductive tract, and their profile varies from that of blood, testis and seminal plasma. The specific role of both prostaglandins in salmonid sperm biology remains unclear.     

Influence of type of dietary fat on the prostaglandin release from isolated rabbit and rat hearts and from rat aortas

It has previously been found (1) that feeding rats a diet containing a high amount of sunflowerseed oil results in a higher coronary flow and left ventricular work of their isolated hearts as compared to hearts of rats fed hydrogenated coconut oil or lard. It was hypothesized that this phenomenon can be explained by an influence of dietary linoleic acid on prostaglandin synthesis in the heart. To verify this hypothesis rabbits and rats were fed for four weeks sunflowerseed oil (SSO), hydrogenated coconut oil (HCO) or lard (L) to a maximum of 30 to 40 per cent of the total digestable energy, and the prostaglandin release from the isolated perfused hearts and rat aortas was determined by gas chromatography and bio-assay (PGI₂).For the isolated hearts of rabbits fed SSO, the release of PGE₂, PGF_2α and 6-oxo-PGF_1α was 1.7, 0.7 and 3.0 ng min⁻¹ g⁻¹ dry weight respectively; when fed L, these values were 2.9, 1.1 and 5.6 ng min⁻¹ g⁻¹. For the isolated hearts of rats fed SSO, HCO or L, the total release of PGE₂, PGD₂, PGF_2α and thromboxane B₂ (TXB₂) was 5.9, 5.8 and 5.6 ng min⁻¹ g⁻¹ respectively; the release of 6-oxo-PGF_1α was 3.4, 5.7 and 6.4 ng min⁻¹ g⁻¹ respectively. Relatively, 26% PGE₂, 13% PGD₂, 8% PGF_2α, 6% TXB₂ and 47% 6-oxo-PGF_1α were released. For the isolated aortas of rats fed SSO or HCO, the release of PGI₂-like activity was 0.37 ± 0.05 and 0.49 ± 0.05 ng min⁻¹ cm⁻². The release of PGI₂-like activity from hearts of EFA-deficient rats was about 20% of that from control hearts.We conclude that, although feeding sunflowerseed oil, with respect to feeding hydrogenated coconut oil or lard, does increase coronary flow and left ventricular work, it does not increase the basal prostaglandin production in the isolated rat or rabbit heart; instead there is a tendency for a lower PGI₂ synthesis.     

Determination of the retinobenzoic acid derivative Am580 in rat plasma by high-performance liquid chromatography

A specific liquid chromatographic method for the determination of 4-[[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbonyl]amino]benzoic acid (Am580) in rat plasma is described. The procedure includes one-step isolation of the compound and the internal standard (naphtol AS) from protein precipitated with acetonitrile, resolution on a reversed-phase column (Supelcosil LC18-DB, 5 μm) with water-acetonitrile-methanol-n-butanol (45:40:14:1, v/v) containing 65 mM ammonium acetate as elution system and UV absorbance detection at 280 nm. The assay was linear over a wide range (25–5000 ng ml⁻¹) and the limit of quantitation was 25 ng ml⁻¹ using 0.2 ml of plasma. It was precise and reproducible enough for pharmacokinetic studies. Application to a preliminary disposition study in the rat indicated that Am580 was characterized by a relatively large apparent volume of distribution (1.1–1.5 l kg⁻¹) and small clearance (8.8–9.7 ml min⁻¹ kg⁻¹). Its pharmacokinetic behaviour was linear within the dose range considered (2 and 10 mg kg⁻¹, i.p.).     

Presence of prostaglandins E2 and A2 in canine gastric secretions

The presence of prostaglandins (PGs) was determined in gastric juice obtained from 3 conscious dogs, provided with a chronic gastric fistula. Outputs of acid (mequiv min^?1) and PGs (pg min^?1) were measured in gastric secretions stimulated by pentagastrin (100 or 200 ng kg^?1min^?1). Prostaglandin activity was estimated, after extraction and thin layer chromatography, by radioimmuno-assay of the PGB formed by treatment with alkali. Tritiated PGs were added to gastric juice for the purpose of correcting for PGs recovery. Using this method, the minimum mass of PGB which could be satisfactorily distinguished from zero was 25 pg. Prostaglandins A₂ and E₂ were present in pentagastrin-activated gastric secretions and averaged (mean ± SE, n = 8) 200.7 ± 18.1 and 260.1 ± 18.0 pg min^?1 respectively. The identity of PGA₂ and PGE₂ was confirmed by gas liquid chromatography combined with mass spectrometry. The amount of PGE₂ converted to PGA₂ during extraction, separation and conversion procedures was estimated from the amount of [³H] PGA₂ found when only [³H] PGE₂ had been added to a sample of gastric juice and averaged 14.5% ± 2.0. Our preliminary results support the possibility that PGE₂ and PGA₂ may be of physiological importance in the regulation of canine gastric secretions.     

Letter to the editor Synthesis of 16-fluoromethylene-prostaglandin F2α

Prostaglandin (PG) E₂, thromboxane (TX) B₂ and the stable breakdown product of prostacyclin, 6-oxo-PGF_1α are present in carrageenin-induced inflammatory exudates. Carrageenin-impregnated polyester sponges were implanted subcutaneously in rats and inflammatory exudates were collected 4–192 h after implantation. The concentrations of cyclo-oxygenase products in sponge fluids was measured by radioimmunoassay after extraction and purification. All three products were detectable after 4 h and reached a peak at 12–24 h. Mean TXB₂ concentrations reached 74 ng/ml at 12 h but decreased to less than 10 ng/ml after 24 h. PGE₂ concentrations were 65 ng/ml at 24 h, after which there was no significant increase and then dropped to about 20 ng/ml between 96 and 192 h. 6-oxo-PGF_1α reached a concentration of 33 ng/ml at 24 h which did not change significantly until levels fell to less than 10 ng/ml between 96 and 192 h. The presence of PGE₂, TXB₂ and 6-oxo-PGF_1α was confirmed by gas-liquid chromatography and mass spectrometry. Total leukocyte numbers increased steadily and were at their highest (116.0 × 10⁶ cells/ml) at 192 h. These results suggest that thromboxanes and prostacyclin, as well as PGE₂, contribute to the acute inflammatory response.     

A novel spectrofluorimetric method for determination of imatinib in pure,pharmaceutical preparation,human plasma,and human urine

The following paper represents a simple, highly sensitive, responsive validated and developed spectrofluorimetric method for estimation of imatinib (IMB) in its pure, commercial preparation, human urine and human blood plasma. The calibration curve was in the range 4–900 ng ml^?1 for pure form and urine and 8–900 ng ml^?1 for plasma in a medium contains carboxymethyl cellulose (CMC) and acetate buffer (pH 5) with excitation wavelength (λ_ex) 230 nm and emission wavelength (λ_em) 307 nm. The limit of detection (LOD) was 0.37 ng ml^?1 for the pure form, 0.64 ng ml^?1 for human urine, and 0.70 ng ml^?1 for human plasma, while the limit of quantitation (LOQ) was 1.2 for pure form, 1.91 for urine and 2.1 for plasma. The suggested method was successfully applied for evaluation of IMB in tablets within 99% mean percentage recovery. The excipients that are usually used as additives in pharmaceutical dosage form did not interfere with the suggested method. The method was efficiently used for estimation of IMB in human urine and human plasma. The effect of some cations that might be present in urine and plasma was also studied. The method was also focused on human volunteers and in vitro drug release.     

Assay of R-apomorphine, S-apomorphine, apocodeine, isoapocodeine and their glucuronide and sulfate conjugates in plasma and urine of patients with Parkinson's disease

Analytical methods are described for the selective, rapid and sensitive determination of R- and S-apomorphine, apocodeine and isoapocodeine and the glucuronic acid and sulfate conjugates in plasma and urine. The methods involve liquid-liquid extraction followed by high-performance liquid chromatography with electrochemical detection. The glucuronide and sulfate conjugates are determined after enzymatic hydrolysis. For the assay of R- and S-apomorphine a 10 μm Chiralcel OD-R column is used and the voltage of the detector is set at 0.7 V. The mobile phase is a mixture of aqueous phase (pH 4.0)-acetonitrile (65:35, v/v). At a flow-rate of 0.9 ml min⁻¹ the total run time is ca. 15 min. The detection limits are 0.3 and 0.6 ng ml⁻¹ for R- and S- apomorphine, respectively (signal-to-noise ratio 3). The intra- and inter-assay variations are <5% in the concentration range of 2.5-25 ng ml⁻¹ for plasma samples, and <4% in the concentration range of 40-400 ng ml⁻¹ for urine samples. For the assay of apomorphine, apocodeine and isoapocodeine, a 5 μm C₁₈ column was used and the voltage of the detector set at 0.825 V. Ion-pairing chromatography was used. The mobile phase is a mixture of aqueous phase (pH 3.0)-acetonitrile (75:25, v/v). At a flow-rate of 0.8 ml min⁻¹ the total run time is ca. 14 min. The detection limits of this assay are 1.0 ng ml⁻¹ for apomorphine and 2.5 ng ml⁻¹ for both apocodeine and isoapocodeine (signal-to-noise ratio 3). The inter-assay variations are 5% in the concentration range of 5-40 ng ml⁻¹ for plasma samples and 7% in the concentration range of 50-500 ng ml⁻¹ for urine samples. The glucuronic acid and sulfate conjugates of the various compounds are hydrolysed by incubation of the samples with β-glucuronidase and sulfatase type H-1, respectively. Hydrolysis was complete after 5 h of incubation. No measurable degradation of apomorphine, apocodeine and isoapocodeine occurred during the incubation. A pharmacokinetic study of apomorphine, following the intravenous infusion of 30 μg kg⁻¹ for 15 min in a patient with Parkinson's disease, demonstrates the utility of the methods: both the pharmacokinetic parameters of the parent drug and the appearance of apomorphine plus metabolites in urine could be determined.     

Plasma transforming growth factor β1 as a biomarker of psoriasis activity and treatment efficacy

Transforming growth factor-β₁ (TGFβ₁) is thought to be an inhibitor of the keratinocyte hyperproliferation associated with psoriasis. The aim of this study was to evaluate plasma TGFβ₁ and TGFβ₂ concentrations in psoriatic patients as possible indicators of treatment efficacy. TGFβ concentrations were measured in the plasma of 26 patients with psoriasis using an enzyme immunoassay and analysed with respect to the psoriasis area and severity index (PASI) before and after treatment with salicylic acid and/or sulphur followed by dithranol ointment. Baseline plasma concentrations of both TGFβ₁ and TGFβ₂ (20.3±2.2 ng ml^?1 and 0.14±0.02 ng ml^?1, respectively) did not differ significantly from control values (18.3±1.6 ng ml^?1 and 0.14±0.03 ng ml^?1, respectively). However, a significant positive correlation (r=0.69) between the baseline PASI and TGFβ₁, but not TGFβ₂, values was demonstrated. The pretreatment TGFβ₁ concentration in patients with a PASI ≥15 (26.6±3.2 ng ml^?1) was significantly higher than control values. There were no significant elevation of pretreatment TGFβ₁ concentrations in patients with a PASI<15, or with respect to TGFβ₂ in both groups. Treatment caused a significant decrease in TGFβ₁, but only in patients with a PASI≥15. Patients with baseline TGFβ₁ concentrations exceeding the mean of the control group had a PASI value that was significantly higher than that of patients with a TGFβ₁ concentration below the mean of the controls. These results confirmed an association between plasma TGFβ₁ concentration and psoriasis severity, and demonstrated its normalization during treatment. Measurement of TGFβ₁ in plasma should be considered as a possible biomarker of psoriasis activity during its management.     

Seasonal changes in the concentration of estrogens and testosterone in the plasma of the stallion

A blood sample was taken from each of 15 stallions at monthly intervals for 14 consecutive months. Plasma concentrations of estrogens and testosterone were measured by radioimmunoassay methods. Estrogens in peripheral blood were present in much higher amounts than testosterone and were principally in a water-soluble, solvolyzable form (> 98%). The major component in the solvolyzed extracts behaved chromatographically as estrone. The mean plasma level (± S.E.) of estrogens averaged across months was 52.9 ± 4.5 ng ml^?1. Individual stallions showed considerable month-to-month variation; for example, single monthly samples ranged from 29.5 to 160.6 ng ml^?1 for the stallion with the highest single value.The highest mean monthly concentration was 69 ± ng ml^?1 in May, and plasma levels were < 40 ng ml^?1 during November and December. For the 11 Thoroughbred stallions in the study, the mean concentrations of estrogens were 73 ± 5.8 ng ml^?1 for May to July and 45 ± 4.1 ng ml^?1 for November to January (P > 0.001).The mean monthly concentrations (± S.E.) of testosterone ranged from 0.22 ± 0.05 to 0.90 ± 0.14 ng ml^?1, and individual samples ranged from < 0.02 to 2.8 ng ml^?1 of plasma. While the highest mean level of testosterone was seen in September, there was a significant difference (P < 0.01) between the values in the breeding season (May–July, 0.73 ± 0.07 ng ml^?1) and the non-breeding season (November–January, 0.38 ± 0.08 ng ml^?1). No marked seasonal changes were observed, however, in testosterone levels in several stallions. It was concluded that plasma estrogen levels may provide a more sensitive index of endocrine function of the testes in the stallion.     

Effects of prostacyclin (PGX) on cyclic AMP concentrations in human platelets

Prostacyclin (PGX) strikingly increases cyclic AMP concentrations in human platelets. Prostacyclin is approximately 10 times more active than PGD₂, 30 times more active than PGE₁ and more than 1000 times more active than its stable end product, 6-oxo-PGF_1α.These results correlate well with the anti-aggregating activity of prostacyclin, compared with PGE₁ and PGD₂.     

Ventilation and oxygen consumption in the hagfish, Myxine glutinosa L.

Ventilation was measured directly in the hagfish, Myxine glutinosa L., by means of an electro-magnetic blood flowmeter. Ventilatory flow and frequency increased from 0.86 ± 0.27 ml·min^?, and 18.2 ± 5.1·min^?, respectively, at 7°C to 1.70 ± 0.20 ml·min^?, and 70.1 ± 9.5·min^? at 15 ·C.Standard oxygen consumption,V?O₂, was measured in non-buried hagfish. V?O₂ was 0.57 ± 0.17μl O₂·g^?1·min^?1 at 7°C, and 0.85 ± 0.12μl O₂·g^?1·min^?1 at 15°C.     

Control of renal and extrarenal salt and water excretion by plasma angiotensin II in the kelp gull (Larus dominicanus)

Summary The osmoregulatory effects of intravenously (i.v.) administered angiotensin II (AII) at dose rates of 5, 15 and 45 ng · kg^–1 · min^–1 were examined in kelp gulls utilizing salt glands and/or kidneys as excretory organs.In birds given i.v. infusion of 1200 mOsmolal NaCl at 0.3 ml · min^–1 and utilizing only the salt glands to excrete the load, infusion of AII for 30 min consistently inhibited salt gland function in a dose-dependent manner.In birds given i.v. infusion of 500 mOsmolal NaCl at 0.72 ml · min^–1 and utilizing both salt glands and kidneys to excrete the load, each dose of AII given for 2 h inhibited salt gland function but stimulated the kidney, so that the overall outputs of salt and water were enhanced and showed significant (2P<0.01) positive correlations with plasma AII.In birds given i.v. infusion of 200 mOsmolal glucose at 0.5 ml · min^–1 and utilizing only the kidneys to excrete the load, low doses of AII (5 and 15 ng · kg^–1 · min^–1) caused renal salt and water retention, whereas a high dose (45 ng · kg^–1 · min^–1) stimulated salt and water output.The actions of plasma AII in kelp gulls support the concept that this hormone plays a vital role in avian osmoregulation, having effects on both salt gland and kidney function. Elevation of plasma AII consistently inhibits actively secreting salt glands, but its effects upon renal excretion depend primarily on the osmotic status as well as on the plasma AII concentration. In conditions of salt and volume loading doses of AII stimulate sodium and water excretion. With salt and volume depletion, the action of AII is bi-phasic with low doses promoting renal sodium and water retention but high circulating levels causing natriuresis and diuresis.     

Responses of aerial ventilation to hypoxia and hypercapnia inChanna argus,an air-breathing fish

Summary The snake-head fish (Channa argus) is an obligate air-breather inhabiting fresh waters in the temperate zone of East Asia.Ventilation of the air-breathing organ and aerial gas exchange were measured in 1 to 2 kg specimens at 15 and 25°C. Additionally, the ventilatory responses to hypoxia and hypercapnia were studied. Aerial ventilation increased from 1.1 to 2.9 mlbtps·kg^–1·min^–1 when temperature rose from 15 to 25°C. Concomitantly, O₂-uptake through airbreathing increased from 0.1 mlstpd·kg^–1·min^–1 (15°C) to 0.28 mlstpd·kg^–1·min^–1 (25°C), whereas aerial gas exchange was less important for CO₂-climination as evident from low gas exchange ratios (0.16 at 15°C, 0.29 at 25°C).Ventilation increases only slightly in response to inspiration of hypercapnic gas mixtures or to hypoxic conditions in water. By contrast, inspiration of hypoxic gas mixtures caused marked increases of ventilation in particular at the higher temperature.Aerial ventilation inChanna is low compared to values for ectothermic pulmonary breathers. However, its ventilatory responses to hypoxia strikingly resemble those of reptiles: The most marked ventilatory response to hypoxia occurs at the higher temperature where the demands for O₂ are greatest.     

Short-term inhibition of prolactin secretion by naloxone treatment in the pregnant gilt

The involvement of endogenous opioids in modulation of prolactin (PRL) secretion during pregnancy in the pig was studied. Twenty-four crossbred pregnant gilts (150 ± 10 kg) were cannulated via the cephalic vein 24–48 h before treatment with 1 mg kg⁻¹ body weight of naloxone (NAL) or 3 ml of saline (CONT) i.v. at Day 40 (NAL, n = 6; CONT, n = 6) or Day 70 (NAL, n = 6; CONT, n = 6) of pregnancy. Blood plasma was collected at 15 min intervals from 1 h before to 3 h after treatment with NAL or saline. At Day 40 of pregnancy, administration of NAL caused a decrease in mean plasma PRL concentrations at 60 min, 120 min and 180 min post-treatment (NAL, 19.1 ± 1.3 ng ml⁻¹, P < 0.05; 15.8 ± 0.6 ng ml⁻¹, P < 0.001; 14.6 ± 0.7 ng ml⁻¹, P < 0.001, respectively) when compared with the CONT group (22.9 ± 0.7 ng ml⁻¹, 21.6 ± 0.6 ng ml⁻¹ and 22.4 ± 0.5 ng ml⁻¹, respectively). Mean plasma estradiol concentration was higher (P < 0.01) in the NAL group during the second and third hour post-treatment than in the CONT group. At Day 70 of pregnancy, infusion of NAL also decreased (P < 0.001) plasma PRL concentrations at 60 min, 120 min and 180 min after treatment (20.1 ± 1.6 ng ml⁻¹, 16.2 ± 1.5 ng ml⁻¹ and 14.8 ± 0.4 ng ml⁻¹, respectively) compared with the CONT group (33.4 ± 1.7 ng ml⁻¹, 34.1 ± 1.3 ng ml⁻¹ and 29.1 ± 0.9 ng ml⁻¹, respectively). Estradiol concentrations were not different (P > 0.05) between groups in this stage of gestation. Mean concentrations of progesterone were similar during the pre- and post-treatment periods in both stages of pregnancy.These data would suggest a possible role of the opioids in modulation of PRL secretion at these stages of pregnancy in the pig.     

Plasma and scales levels of interleukin 18 in comparison with other possible clinical and laboratory biomarkers of psoriasis activity

Abstract

The aim of the study was to assess plasma and scales levels of interleukin (IL) 18 collected from psoriatic patients with different disease activity. IL-18 concentrations were measured using an enzyme immunoassay in the plasma and scales of 34 patients with chronic plaque type psoriasis. IL-18 levels were analysed with respect to plasma-transforming growth factor β₁ (TGF-β₁), the disease duration and the duration of the present relapse, and psoriasis area and severity index (PASI). Plasma IL-18 concentration varied from 90 to 1300 pg ml^?1 and means (368.2±42.4 pg ml^?1) were significantly elevated in comparison with healthy controls (205.9±31.8 pg ml^?1). The presence of IL-18 was also demonstrated in scales from skin lesions. Treatment caused a significant decrease of plasma IL-18 concentration to 250.2±13.8 pg ml^?1. There was a significant correlation between plasma IL-18 levels and PASI values (r=0.554). There was no correlation between IL-18 concentration in scales and PASI, between IL-18 concentrations in plasma and scales, and between plasma IL-18 and the disease duration or duration of present relapse. Plasma TGF-β₁ concentration demonstrated a significant correlation with PASI (r=0.353), but not with IL-18 levels in plasma (r=0.063) and scales (0.141). The sum of plasma levels of IL-18 and TGF-β₁ divided by the optimal coefficient demonstrated a statistically significant correlation with the highest r-value. The findings confirm an association between plasma IL-18 concentration and psoriasis severity. Moreover, it was shown that combined measurement of IL-18 and TGF-β₁ in plasma can be considered as a possible biomarker of psoriasis activity.     

Specific changes in the in vitro production of prostanoids by the ovine cervix at parturition

A method of tissue superfusion has been used to measure $\text{in vitro}$ prostanoid production by the ovine cervix during late pregnancy and at parturition. In late pregnancy (105–135 days of gestation) cervical tissue produced relatively large amounts of prostaglandin E (PGE); in comparison, the production rates of prostaglandin F (PGF), 13, 14-dihydro-15-oxo-prostaglandin F (PGFM) and 6-oxo-prostaglandin F_1α were generally low. Thromboxane B₂ (TXB₂) production was minimal and often unmeasurable. There were significant increases in the production rates of PGE and 6-oxo-PGF_1α by cervical tissue taken immediately after delivery, when compared to late pregnancy. Mean production rates of PGE increased from 19.8 ± 4.1 to 43.8 ± 7.4 ng/g. dry wt./min; 6-oxo-PGF_1α production rates increased more than three-fold from 10.0 ± 2.7 to 34.6 ± 9.8 ng/g. dry wt./min (means ± S.E.M.). There were no significant differences in the rates of production of PGF, PGFM and TXB₂ by the two groups.