Differential ontogeny of divalent cation effects on rat brain delta-, mu-, and kappa-opioid receptor binding

The effect of the divalent cations, Mn2+, Mg2+ and Ca2+ on rat forebrain delta-, mu- and kappa-receptor binding was examined during postnatal development. It was found that delta-receptor binding, assessed with [3H]D-Ala2-D-Leu5-enkephalin ([3H]DADLE) (+ 10 nM D-Ala2- MePhe4-Gly-ol5-enkephalin (DAMGE)), was stimulated by the 3 cations in a dose- and developmental time-dependent manner. delta-Binding was most sensitive to the cations during the first week postnatal, prior to the appearance of high-affinity delta-binding. In contrast, inhibition of mu-receptor binding ([3H]DAMGE) by divalent cations appeared early in development and remained constant throughout the postnatal period. Divalent cation inhibition of kappa-binding ([3H]ethylketocyclazocine ([3H]EKC) + 100 nM DAMGE and 100 nM DADLE) appeared after the second week postnatal. These results demonstrate that the characteristics and postnatal development of divalent cation modulation of mu-, delta- and kappa-binding is distinctly different. Thus, the neonate may be a good model system to examine the binding properties and functions of delta- and kappa-receptor subtypes.     

Surgical treatment of intercostal hernia with implantation of polypropylene mesh

The intercostal hernia of the lung is a very rare extraordinary disease that requires operation because of the complaints and potential complications. The authors review cases of their operations and analyze the subsequence and treatment. Three patients have been treated for intercostal lung hernia in our treatment. The causes of this disease were a previous thoracotomy in one case and fits of coughing in the other two cases. The diagnosis was set up on the grounds of the specific clinical symptoms, thoracic X-ray and CT scan. The hernia was dissolved with percostal stitches and with the suture of the thoracic musculature in two cases. Plastic operation of the thoracic wall by implanting a polypropylene surgical mesh (Prolen, Ethicon, Johnson & Johnson) was performed in the case of the third patient and later in the first two patients due to recrudescence. In one case the authors were constrained to resect the dystelectasial lung in the hernial sac. The three patients had been operated five times. Relapse of hernia was detected in two patients, in whom the intercostal space had been reconstructed with percostal stitches. We did not detect any relapsing in those two patients at 33 and 66 months after the second operation with mesh implantation. The third patient who got mesh implant immediately did not relapse 12 months after the operation. Intercostal lung hernia is an indication of operation. A plastic operation of the thoracic wall combined with the implantation of a surgical mesh is recommended to close the hernial orifice, which is suitable for treating both primary and relapsed hernias. Recurrence is rare in those patients treated with this method.     

Immunocytochemical identification of outer segment proteins in the rd chicken

Immunoreactivities of two monoclonal antibodies (MAbs) that recognize cone photopigments were tested in the retinas of congenitally blind retinal degenerate (rd) chicks and compared to normally sighted carrier chicks, heterozygous for the mutation. MAb OS-2 had been previously determined to label rod and most cone outer segment membranes in normal chick retinas and is believed to bind to an epitope that is common to several photopigments in chickens. MAb COS-1 labels specifically middle-to-long-wavelength-sensitive cone photopigments in a number of vertebrate species. In rd chicks MAb OS-2 labeled the same number of rod outer segments at the same densities as carrier chicks. However, cone outer segments were less frequently and significantly less heavily labeled with this MAb at all ages tested (1 day, 1 week and 2 weeks post hatching). MAb COS-1 labeled the same number of cone outer segments in both rd and carrier retinas at 1 day of age, however, those outer segments that were labeled in rd specimens had significantly fewer gold particles on them. At both 1 week and 2 weeks of age, rd chick retinas had a significant reduction in numbers of cone outer segments labeled by COS-1. These findings support the hypothesis that the cone photopigment protein is abnormal in the rd chick model of hereditary blindness and retinal degeneration.     

Local anesthetics: lipophilicity, charge, diffusion and site of action in isolated neuron

Sodium channel blocking activity was measured in a series of newly synthesized tertiary amine compounds and their quaternary derivatives applied externally on internally in the rat sensory neuron. The large difference in effectiveness of the quaternary compounds on external and or internal application became smaller and even disappeared with increasing lipophilicity of the compounds. No such difference was observed in the tertiary analogs. It was concluded that lipophilicity played an important role in determining the channel blocking activity of externally applied quaternary compounds. The results suggest that, in addition to the neutral form, highly lipophilic amine local anesthetics may penetrate into and/or pass across the neuronal membrane probably as electroneutral ion pair complexes consisting of the cationic form and an appropriate anion. The present results support our hypothesis which stresses, in addition to dissociability, the role of lipophilicity of amine local anesthetics in the pH dependence of their effect.     

Similar outcome for cryopreserved embryo transfer following GnRH-antagonist/GnRH-agonist, GnRH-antagonist/HCG or long protocol ovarian stimulation

The pregnancy rates after triggering of final oocyte maturation with gonadotrophin-releasing hormone (GnRH) agonist in GnRH-antagonist ovarian stimulation protocols are lower than those following triggering with human chorionic gonadotrophin (HCG). Furthermore, lower pregnancy rates following GnRH-antagonist protocols compared with long GnRH-agonist protocols have been reported. The differences might be due to an impact on oocyte number and quality or on the endometrium. If any stimulation protocol had a negative impact on oocyte quality, then further evidence of this effect would be observed following frozen-thawed embryo transfer originating from that stimulation cycle. The outcome of frozen-thawed embryo transfer was retrospectively analysed using the long protocol with triptorelin depot 3.75 mg (n = 215) or 0.1 mg/day (n = 83), or GnRH-antagonist protocol with either HCG (n = 69) or GnRH-agonist (n = 25) for final oocyte maturation. The outcomes measured were implantation rate, clinical pregnancy rate, ongoing pregnancy rate and embryo survival rate. All outcomes were similar in the four groups. It is concluded that the potential for frozen-thawed embryos to implant and develop following transfer is independent of the GnRH-analogue and the final oocyte maturation protocol used in the collection cycle. Lower IVF embryo transfer success using GnRH-antagonist/GnRH-agonist protocol does not appear to be related to an adverse effect on oocyte quality.     

Magnesium-orotate supplementation for idiopathic infertile male patients: a randomized, placebo-controlled clinical pilot study.

A randomized, placebo-controlled clinical pilot study was performed in order to examine the effect of magnesium-orotate in male idiopathic infertility. Ten males were treated daily for 90 consecutive days with 3000 mg magnesium-orotate (Magnerot) tablets (Group M). As a control, ten other males were treated in the same way with placebo (Group P). Conventional microscopic sperm characteristics (sperm concentration, motility ratio, total number of motile sperm cells, normal morphology ratio), plus total and ionized magnesium levels in seminal plasma and blood serum were evaluated both prior to treatment and on day 90, at the conclusion of the study. No significant changes in sperm characteristics, blood ionized or total Mg, or ejaculate total Mg levels were detected. However, ejaculate ionized Mg levels increased in Group M from 0.18 +/- 0.05 to 0.30 +/- 0.05 (mmol/l; mean +/- SD, p < 0.05). Within the observation period of 3 months, one pregnancy occurred in the partner of a male from Group M. In conclusion, magnesium-orotate treatment at a dose of 3000 mg/day leads neither to a significant improvement of sperm variables nor does it increase the pregnancy rates of female partners of treated males as compared to those of controls. Thus, magnesium-orotate treatment was not shown to be effective therapy for idiopathic male infertility.     

pH dependence of the blocking activity of carbisocaine and its derivatives

The blocking activity and pH dependence of carbanilate local anaesthetics, carbisocaine and its homologues, were tested on isolated rat sciatic nerves at pH 6.0, 7.2 and 8.4. Carbisocaine blocked the compound action potential more strongly than the derivatives with shorter alkoxysubstituents. The blocking potency of shorter derivatives increased with the rise of external medium pH, whereas the activity of carbisocaine increased with decreasing external pH. Quaternary compounds applied in the external medium were able to block the action potential, but in higher concentrations and with a longer half-time than their tertiary analogues. The blocking potency of quaternary derivatives correlated well with the length of the alkoxysubstituent and thus also with their lipophilicity. Extracellular pH did not consistently change the inhibitory effect of quaternized derivatives. These observations support the view that the lipophilicity of local anaesthetics is one of the possible factors determining their anaesthetic activity and the pH dependence of their effect.