Anonymous or identity-registered sperm donors? A study of Dutch recipients' choices

BACKGROUND: The aim of the present study was to gain insight into parents' own donor preferences within a system offering the choice between an anonymous and identity-registered donor. A comparison was made between recipients choosing for an anonymous donor (AD choosers) and those choosing for an identifiable donor (ID choosers) with regard to their sexual orientation, demographic characteristics, disclosure issues and infertility distress. METHODS: Data from 105 couples (61% heterosexual, 39% lesbian) were registered on a standardized form during implication counselling sessions previous to treatment. RESULTS: Sixty-three per cent of the heterosexual couples and 98% of the lesbian couples had chosen an ID donor. Major differences between ID and AD choosers were identified. Among the ID choosers secrecy towards the child was no option, whereas 83% of the AD choosers did not intend to inform their child. Compared with heterosexual ID choosers, AD choosers were more distressed about their infertility and had a lower educational level. CONCLUSION: Legislation imposing ID donors appears to be acceptable for the majority of this study population. For a vulnerable group of heterosexual couples, who remained secretive about the use of a donor, adaptation to the new system is not self-evident.     

Acidic ATP activates lymphocyte outwardly rectifying chloride channels via a novel pathway

Using whole-cell patch-clamp techniques we found that ATP activated an outwardly rectifying current in Daudi human B lymphoma cells under acidic conditions. The substitution of Cl^– for gluconate^– shifted the reversal potential, while Cl^– channel blockers, 4,4-diisothiocyanostibene-2,2-disulfonic acid (DIDS) and 9-anthracene carboxylic acid (9-AC), blocked the current, indicating that ATP induces this current by activating the outwardly rectifying chloride channel (ORCC). The effect of ATP on ORCC was mimicked by ADP, but not by other P2 receptor agonists such as ATPS (a poorly hydrolyzable analog of ATP), 2,3-O-benzoyl-4-benzoyl-ATP (BzATP), and UTP. The ATP-induced ORCC current was completely blocked by 100 M suramin (a P2 receptor antagonist), and was partially blocked by 100 M pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid tetrasodium (PPADS), which is another P2 receptor antagonist. Neither inactivation of G proteins nor elimination of extracellular Ca²⁺ affected the ATP-induced current, indicating that G protein-coupled P2Y receptors and Ca²⁺-permeable P2X receptors are not involved. Based on the pharmacological profile and the fact that acidic conditions are required for ATP to activate the ORCC, we suggest that acidic ATP activates the lymphocyte ORCC via a novel pathway, which is not associated with any previously described purinergic receptors.     

输血后丙型肝炎病毒非结构区抗体和丙氨酸转氨酶的动态分析

利用重组的丙型肝炎病毒非结构区（ＨＣＶＮＳ５）抗原建立了酶免疫试验（ＥＩＡ），对２５例输血后丙型肝炎进行了不同区抗体及丙氨酸转氨酶（ＡＬＴ）的动态研究，同时对１５６例慢性丙型肝炎患者血清进行ＨＣＶＲＮＡ和抗－ＮＳ５平行检测，两者符合率为６４．１％。抗－ＮＳ５抗体首次检出时间为３０～５７５天（１８２．９±１６８．５），晚于ＡＬＴ异常和其他区抗体的出现时间。在感染后１，３，６，１２和２４个月后抗－ＮＳ５的阳性率分别为２８％，４０％，５２％，６８％和７６％。抗－ＮＳ５的动态变化类型为四种：一过性阳性、间歇性阳性、持续性阳性和２年内持续阴性     

Adjustment of metabolism,catecholamines and β-adrenoceptors to 90 min of cycle ergometry

Adrenaline infusion of 0.1 g · kg^–1 · min^–1 in healthy volunteers results in an increase of hepatic glucose production, an increase of the absolute number of occupied -adrenoceptors and specific changes in metabolism. To compare these effects with the changes induced by an endogenous catecholamine release, we investigated healthy volunteers during cycle ergometry. After fasting at least 14 h seven healthy subjects exercised for 90 min at an intensity of 20% below their individual anaerobic threshold. The rate of glucose production as well as the turnover rates of alanine and leucine were calculated using stable isotope tracers. High and low affinity -adrenergic binding sites on lymphocytes were determined by an equilibrium binding assay with (–)¹²⁵ Iodocyanopindolol. After 90 min of cycling the rate of appearance of glucose increased significantly from means of 2.0 (SD 0.2) to 2.65 (SD 0.50) mg · kg^–1 · min^–1 with unchanged blood concentrations of glucose and lactate. The flux of the amino acids alanine and leucine decreased significantly from means of 0.91 (SD 0.21) to 0.62 (SD 0.14) mg · kg^–1 · min^–1 and from 0.40 (SD 0.05) to 0.32(SD 0.04) mg · kg^–1 · min^–1, respectively. The mean free fatty acid concentration increased significantly from 0.65 (SD 0.33) to 1.27 (SD 0.45) mmol · l^–1 during the endurance trial. The increase of glucose turnover and the decrease of amino acid flux point to a metabolic shift towards enhanced utilization of free fatty acids. Adrenaline and noradrenaline concentrations showed a moderate but significant increase from means of 0.61 (SD 0.20) to 0.99 (SD 0.36) nmol · l^–1 and from 2.27 (SD 0.75) to 3.46 (SD 0.38) nmol · 1^–1, respectively. The number of high affinity -adrenergic binding sites per cell (-adrenoceptors) nearly doubled from 770 (SD 130) to 1490 (SD 150) during 90 min of cycling. The observed endogenous plasma catecholamine concentrations were not sufficient to change significantly the relative receptor occupancy. This would seem to indicate that the aerobic exercise induced effects depended more on the absolute number of occupied -adrenoceptors than on their relative receptor occupancy. When compared to the results of the adrenaline infusion experiment the increases of the hepatic glucose production and the increase of -adrenoceptors were very similar in both groups despite ten times higher adrenaline plasma concentrations in the infusion group. This would seem to indicate that -adrenoceptors mediated effects do not correlate with catecholamine plasma concentrations.     

Intra-uterine insemination versus cyclic, low-dose prednisolone in couples with male antisperm antibodies

A total of 46 couples with male immunological infertility enteredthe trial at the infertility clinic of the Family Federationof Finland. The men all showed a positive mixed antiglobulinreaction to immunoglobulin G in their semen; 31 men were alsotested for sperm-bound IgA immunoglobulins by flow cytometry.Serum antisperm antibodies were checked in a tray agglutinationtest. The women showed normal reproductive endocrinology andat least one patent Fallopian tube. The couples were randomizedto undergo either up to three intra-uterine inseminations (IUI),or timed intercourse with cyclic, low-dose (20 mg) prednisolonetherapy of the men. Cross-over was carried out if no pregnancyoccurred in the first stage. Timing of ovulation was based onurinary luteinizing hormone assay and transvaginal ultrasonographicmeasurements. In all, 40 couples either completed the studyor the female partner conceived. IUI was significantly better(P = 0.04) with nine pregnancies than timed intercourse withprednisolone (one pregnancy). There were no significant associationsbetween antibody levels, sperm count or motility versus theincidence of pregnancy. In male immunological infertility, well-timedIUI is an effective treatment method: results are obtained rapidlyand steroidal side-effects can be avoided.     

Serum contains a potent factor that decreases β-adrenergic receptor-stimulated L-type Ca2+ current in cardiac myocytes

L-type Ca²⁺ current (I _Ca) was measured in cultured atrial myocytes from hearts of adult guinea-pigs using whole-cell voltage clamp. Potentiation of I _Ca induced by -adrenergic stimulation (isoprenaline 2· 10^–7 M) could be completely antagonized by diluted sera (1100 v/v). Half-maximal inhibition of -receptorstimulated I _Ca occurred at about 11000. Basal I _Ca was not affected by serum. Atropine in a concentration (10^–6M) that completely antagonized the anti-adrenergic effect of acetylcholine (ACh, 2·10^–6 M) did not interfere with the effect of serum. In cells dialysed with cyclic adenosine monophosphate (cAMP)-containing (10^–4 M) pipette solution, potentiated I _Ca was insensitive to both ACh and serum. Preincubation of the myocytes with pertussis toxin almost completely abolished the anti-adrenergic effects of both ACh and serum. The potency of serum was not reduced by dialysis. It is concluded that serum contains a factor which, like ACh, inhibits -receptor-stimulated adenylyl cyclase via G_iprotein.A preliminary report of this work has appeared in abstract form [11]     

Inhibition of ω-conotoxin-sensitive Ca2+ channel currents by internal Mg2+ in cultured rat cerebellar granule neurones

The effects of changing the intracellular concentrations of either free Mg²⁺ ions ([Mg²⁺]_i) or Mg²⁺-bound adenosine triphosphate ([Mg · ATP]_i) on Ca²⁺ channel currents were assessed in cultured rat cerebellar granule neurones using the whole-cell patch-clamp technique. Raising [Mg²⁺]_i from 0.06 mM to 1.0 mM inhibited Ca²⁺ channel currents by approximately 50%. The action of -conotoxin GVIA (-CgTX), a selective inhibitor of N-type Ca²⁺ channels was also investigated. With increasing [Mg²⁺]_i, the proportion of current irreversibly blocked by -CgTX was reduced, and was negligible (approximately 5 pA of current) in the presence of [Mg²⁺]_i values of 0.5 mM or greater. Block of the -CgTX-sensitive current accounted for the reduction in total current by concentrations of [Mg²⁺]_i to 0.5 mM. Raising [Mg²⁺]_i had no effect on the rate of decay of Ca²⁺ currents, but did produce a negative shift in current activation, possibly due to a non-specific interaction with negative surface charge. Altering [Mg · ATP]_i from 0.3 to 5.0 mM caused a twofold increase in the size of currents without affecting the proportion of current sensitive to -CgTX. [Mg²⁺]_i was also effective in inhibiting the Ca²⁺ channel current following potentiation by increasing [Mg · ATP]_i. These data suggest that -CgTX-sensitive current in these cells is selectively inhibited by internal Mg²⁺ whereas both -CgTX-sensitive and -resistant components of current are potentiated by internal Mg · ATP. The mechanism by which Mg²⁺ inhibits N-type channels is unclear, but may involve an open channel block.     

A prospective randomized comparison of levonorgestrel with the Yuzpe regimen in post-coital contraception

A prospective randomized study was conducted at the Family PlanningAssociation of Hong Kong to compare the efficacy of the Yuzperegimen and levonorgestrel (0.75 mg for two doses 12 h apart)in post-coital contraception. A total of 424 subjects were recruitedinto the Yuzpe group and 410 subjects into the levonorgestrelgroup; 77 subjects in the Yuzpe group and 79 subjects in thelevonorgestrel group had further acts of intercourse duringthe treatment cycle. Fifteen pregnancies (3.5%) occurred inthe Yuzpe group and 12 pregnancies (2.9%) in the levonorgestrelgroup. After excluding the patients who had further acts ofintercourse, the failure rates in the Yuzpe group and the levonorgestrelgroup were 2.6 and 2.4% respectively. The incidence of nausea,vomiting and fatigue in the Yuzpe group was significantly higherthan those in the levonorgestrel group. We conclude that levonorgestrelis an effective drug for post-coital contraception with a lowerincidence of side-effects than the Yuzpe regimen.     

Third trimester iron status and pregnancy outcome in non-anaemic women; pregnancy unfavourably affected by maternal iron excess

A prospective observational study was performed on 488 women with haemoglobin >/=10 g/dl at booking to examine the relationship between serum ferritin concentration quartiles at 28-30 weeks gestation with maternal characteristics, pregnancy complications and infant outcome. While there was no difference in the maternal characteristics or gestational age, the infant size decreased significantly and progressively from the lowest to the highest quartile. Despite a significant difference in the incidence of multiparous women, there was no difference in the incidence of most complications except for prelabour rupture of the membranes and infant admission to the neonatal unit. Compared with the other three quartiles, the highest quartile was associated with increased risk for preterm delivery and neonatal asphyxia, while the lowest quartile was associated with decreased risk of pre-eclampsia, prelabour rupture of the membranes, and infant admission to the neonatal unit. Overall, ferritin quartiles were correlated with other parameters of iron status and red cell indices, and ferritin concentration was inversely correlated with infant birthweight. Our findings suggested that maternal ferritin concentration is primarily a reflection of maternal iron status, and a high level is associated with unfavourable outcome. The rationale of routine iron supplementation in non-anaemic women needs to be re-examined.     

Amiloride enhances the secretion but not the synthesis of renin in renal juxtaglomerular cells

In this study we have examined a potential role of the sodium/proton exchange system in the regulation of renin secretion. We found that the inhibitors of the Na⁺/H⁺ antiport, amiloride (1 mM) and ethylisopro-pylamiloride (EIPA, 50 M), led to a 125% increase of renin secretion from cultured mouse juxtaglomerular cells. The stimulatory effect of EIPA on renin secretion was dependent on the extracellular concentrations of sodium and hydrogen ions. While lowering the extracellular pH from 7.3 to 7.0, and lowering [Na⁺]_e from 130 mM to 5 mM had no effect on basal renin release, it markedly attenuated or even blunted the effect of EIPA on renin secretion. The stimulatory effect of forskolin on renin secretion, however, was not altered by decreases of extracellular pH and of sodium. Inhibition of basal renin release was achieved with angiotensin II (1 M). In the presence of EIPA the inhibitory effect angiotensin II was markedly attenuated. Although effective on renin secretion, neither amiloride nor EIPA exerted a significant effect on the de novo synthesis of renin in cultured mouse JG cells. These findings are compatible with the idea that an amiloride-sensitive transport process, presumably the Na⁺/H⁺ exchanger, acts indirectly as an inhibitory signal transduction system for renin secretion from renal juxtaglomerular cells.