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The article presents a study that examines the effectiveness of buprenorphine when added to cognitive behavioural treatment in patients with heroin dependence. It describes the method of the study that observes 40 patients with an opiate dependence. It details the findings of the study which indicates that buprenorphine added to intensive cognitive behavioural therapy can improve outcome in patients with heroin dependence.

The seminal adenosine triphosphate (ATP) content was determined by bioluminescence after treatment with trichloroacetic acid (TCA) in 81 semen samples 1.5 h after ejaculation obtained from men attending our fertility clinic, and selected to contain either 20% or less spermatozoa with good progressive motility (n = 22), or 60% or more spermatozoa with good progressive motility (n = 59) (Study I), and in 18 semen samples from fertile men 30 min and 3.5 h after ejaculation (Study II). The latter samples were divided into 2 equally large groups according to sperm motility. In Study I the mean sperm ATP concentration was significantly higher in the semen samples with bad motility (0.63 nmol per living spermatozoa x 10(-6)) than in semen samples with good motility (0.39 nmol per living spermatozoa x 10(-6); P less than 0.01). In Study II the ATP concentration per living spermatozoa was also lower in the group with the best motility in comparison with the spermatozoa with lower motility (P less than 0.01), both 30 min and 3.5 h after ejaculation. During the 3-5 h incubation the sperm ATP concentration decreased by 21% (P less than 0.01) in the former group of samples but remained unchanged in the latter group. The results indicate that, in semen samples with highly motile spermatozoa, the consumption of ATP is higher than in semen samples with impaired sperm motility. It is therefore essential that the time between ejaculation and ATP measurement is as short as possible to obtain comparable results. Repeated ATP measurements in combination with an analysis of the number of living spermatozoa, may provide further information on the fertilizing capacity of spermatozoa.

Five men with cystic fibrosis delivered semen samples which were analysed for the content of the four main groups of prostaglandins (PGs). No PGs could be found in any of the specimens. The results of the present study provide further evidence that the seminal vesicles constitute the dominant site of production of PGs in human semen.

A comparison of different procedures for adenosinetriphosphate (ATP) determination in whole ejaculates showed that it is advantageous to treat the specimens with trichloroacetic acid (TCA before quantification of ATP by bioluminescence). Semen samples from different men were found to cause varying degrees of inhibition of the luciferin-luciferase reaction. Hence, internal ATP standard had to be added to each sample to allow calculation of endogenous ATP. Mean recovery of ATP was 98.5%. The intrassay and interassay coefficients of variation were 3.0% and 3.9%, respectively. A correlation between the number of progressively motile spermatozoa and the ATP concentration was found (r = 0.89, P = 0.0005, n = 22). The mean level of ATP was 0.49 nmol/living sperm X 10(6) in semen with normal sperm motility and sperm density obtained from 22 men attending our fertility clinic. Seminal ATP was detected only in the spermatozoa.

Our knowledge of the importance of PGs for the physiological regulation of male and female reproductive organs is rapidly increasing. In this presentation two examples have been described in detail. Data are accumulating indicating that PGs in semen are of major importance for sperm motility and the functional capacity of sperms. Recording of intrauterine pressure in early pregnant patients has shown that treatment with an antiprogestin depriving the myometrium from progesterone influence, will induce regular uterine contractions. The data support the hypothesis that the uterine activity is regulated by the balance between PGF2 alpha and progesterone.

Several hours following administration of long acting vaginal suppositories containing 3.0 mg of 15-methyl-PGF2 alpha for interruption of second trimester pregnancies there is an up to 10-fold increase in endogenous production of PGE2 and PGF2 alpha before abortion as reflected by gas chromatographic-mass spectrometric determination of the major plasma metabolites of PGE2 and PGF2 alpha. The data suggest that this increased formation of endogenous prostaglandins contributes to the induced uterine activity during the latter part of the abortion process.

A single 1 mg dose of prostaglandin (PG) E2 was given orally to 19 men. Ejaculates were obtained 90 minutes and 24 and 48 hours thereafter. Before treatment, each man delivered another three semen samples with the same time intervals as during the study period. PGE2 was also administered to seven men during naproxen treatment and ejaculates were sampled as above. PGE2 did not influence the 90 minutes' posttreatment ejaculates, but after 24 hours there was a significant (P less than 0.05) decrease in sperm counts as compared to the control samples. The change in sperm count was suggested to be due to an effect of PG on the contractile elements in the deferent duct. Sperm motility, viability, and morphology as well as semen volume and adenosine triphosphate (ATP) content remained unchanged. The total semen PGE content was increased 24 hours after treatment from 169 micrograms/ejaculate to 213 micrograms/ejaculate (P = 0.02). In the combined PGE2/naproxen treatment the PGE levels were significantly (P less than 0.05) elevated in the ejaculate 48 hours after treatment. The increase may indicate an increased de novo synthesis of prostaglandins. Based on the results from the analysis of the composition of the 19-hydroxy PGF-isomers with and without naproxen treatment, it is speculated that oral PGE2 influences the cyclo-oxygenase activity.

Human seminal plasma contains eight different prostaglandins belonging to the F series, i.e. PGF1 alpha, PGF2 alpha, 19-hydroxy-PGF1 alpha, 19-hydroxy PGF2 alpha, as well as the corresponding 8 beta-isomers. A systematic description of the mass spectrometric fragmentation of the 8 beta-isomers has not been previously reported. In the present study the prostaglandins were separated from human seminal plasma and analysed as methylester, trimethylsilylethers with gas chromatography mass spectrometry. All the eight F and 19-hydroxy F prostaglandins fragmented in the same manner, but the relative abundances of the formed ions varied in a typical way. Thus, the mass spectra of 8 beta-PGF1 alpha and 8 beta-19-hydroxy PGF1 alpha differed clearly from those of their 8 alpha-isomers, which could be used for identification and should be considered in selected ion monitoring. The ratio between the seminal plasma levels of 8 beta- and 8 alpha-isomers of 19-hydroxy F1 alpha was much higher than the corresponding ratio for the PGF1 alpha.

Whole ejaculates were examined for their content of prostaglandins (PGs) during medication with 250 mg naproxen three times daily for 2 weeks. Six volunteers delivered semen samples before, periodically during, and after the period of medication. During treatment with naproxen, the concentration of PGE, PGF, 19-hydroxy-PGE, and 19-hydroxy-PGF significantly decreased. One week after cessation of medication the PG concentration had returned almost to that found before treatment. The four 19-hydroxy-PGF compounds could be determined separately and the relation between them estimated. The proportion of 8 alpha-19-hydroxy-PGF2 alpha increased, whereas that of 8 beta-19-hydroxy-PGF1 alpha decreased significantly during the medication period. No significant influence of the treatment on sperm density or motility could be observed. It is concluded that treatment with naproxen, a potent inhibitor of PG synthesis, significantly reduces the concentration of all PGs present in human seminal fluid. The implication of the effect on human fertility is discussed.

The efficacy and safety of different oral doses of PGE2 in tablet form were evaluated in 30 women admitted to the hospital for labor induction at or near term. The aim was to select a recommendable dose schedule based on recording of uterine contractility, clinical outcome and measurement of the resulting plasma levels of the two prostaglandin metabolites 15-keto-13, 14-dihydro-PGE2 and 15-keto-13, 14-dihydro-PGE2 alpha by gas-chromatography-mass spectrometry and by radio-immunoassay. Measurements of uterine contractility and of plasma levels of the PGE2 metabolite both showed that the preferable interval between oral doses of PGE2 tablets is one hour. Following 1.0 mg PGE2, the plasma concentration peaked after 45 to 60 minutes and had returned to approximately pretreatment levels after 120 minutes. With a two-hour interval between doses there was above all a decreased frequency of contractions in the last part of the interval. No such variation in the contractility pattern was seen when 1.0 mg PGE2 was administered every hour. When the individual dose was increased to 2.0 mg, signs of overstimulation of uterine contractility were observed. The plasma concentration of the E2 metabolite increased in accordance with the oral dose. A slow rise in the plasma concentrations of the E2 and F2 alpha metabolites was found some hours following initiation of treatment, possibly indicating an increased endogenous prostaglandin biosynthesis, probably secondary to the stimulated uterine contractility.

Prostaglandins E, F, 19-hydroxy E, and 19-hydroxy F (PGE, PGF, 19-OH-PGE, and 19-OH-PGF) in human semen were determined by a new chemical method. The method allows liquefaction to occur, a prerequisite for simultaneous estimation of PG concentration and sperm characteristics in the same ejaculate. The present study showed also that the variation in PG concentration between different individuals was more pronounced than in repeated ejaculates from the same individual. Sperm density and sperm motility seemed related to PG concentration. A high density was associated with a low PG concentration. The concentration of 19-OH-PGE was higher and that of 19-OH-PGF lower in ejaculates with a normal sperm motility than in those with an abnormal motility. It seems that functional requisites of sperm depend upon optimal seminal PG concentration.

The aim of the present study was to evaluate the effect of addition of physiologic amounts of different prostaglandins normally present in semen, on sperm motility, on sperm penetration capacity in cervical mucus in vitro, and on the adenosine triphosphate (ATP) concentration in semen. Semen samples were obtained from volunteers who were attending the fertility outpatient clinic. Sperm motility was measured on a video recorder with a built-in timer, sperm penetration by the Kremer test, and ATP by bioluminescence assay. The addition of 19-hydroxy prostaglandin (PG) E to ejaculates positively stimulated sperm motility and sperm penetration capacity. The opposite effect was observed with 19-hydroxy PGF. PGE1, PGE2, and PGF2 alpha had no effect on either parameter, while PGF1 alpha reduced the sperm motility. The addition of 19-hydroxy PGE to ejaculates increased and the addition of 19-hydroxy PGF reduced semen concentrations of ATP. However, only the last-mentioned effect was statistically significant (P less than 0.05). It is suggested that, in particular, 19-hydroxy PGE and 19-hydroxy PGF are important regulators of sperm motility and that the effect may be mediated via effects on the ATP content in the spermatozoa.

The plasma concentration of 13,14-dihydro-PGF2 alpha during menstruation were determined by gas chromatography in 6 non-dysmenorrheic and 10 dysmenorrheic women. Nine out of 10 dysmenorrheic women were found to have increased levels (greater than 50 pg/ml) of the metabolite compared with mean level 25 pg/ml for non-dysmenorrheic women. All 9 women with elevated PGF2 alpha-metabolite levels responded favourably to treatment of dysmenorrhea with prostaglandin synthetase inhibitors. Determinations of PGF2 alpha in the endometrium carried out by gas chromatography-mass spectrometry showed 4 times higher concentrations in 5 dysmenorrheic women compared with 5 non-dysmenorrheic subjects. Treatment of dysmenorrhea with placebo or naproxen 250 mg and 500 mg in 6 patients resulted in decrease in tonus and amplitude of the contractions with a more rapid effect following administration of naproxen 500 mg while no effect was seen in 5 out of 6 patients following administration of placebo.