Dissociation of acetylcholine- and cyclic GMP-induced currents inXenopu oocytes

InXenopus follicular oocytes, activation of muscarinic receptors evokes a slow potassium current (H-response); a similar current is evoked by intracellular injection of cyclic guanosine 3,5-monophosphate, cGMP (Dascal et al. 1984). We have tested the hypothesis that cGMP may be the second messenger that mediates the opening of K channel by acetylcholine (ACh). ACh elevated the intracellular level of cGMP with a time course similar to that of the development of the muscarinic H-response; maximal increase in cGMP concentration above the control was about 0.2 pmole/oocyte. The amount of injected cGMP that produced a detectable K current (threshold dose) varied between 0.5 and 3 pmole/oocyte. At low doses of cGMP, the slope of log dose-log response curve was about 2.5, suggesting involvement of a biochemical process with a positive cooperativity of at least 3. Higher doses of cGMP evoked, in addition to the outward current, an irregular, rapidly developing, long-lasting inward current, that never reached amplitudes comparable to those of ACh-evoked Cl currents. The K current elicited by cGMP was insensitive to elevation or depletion of external Ca. It was potentiated by isobutylmethylxanthine (IBMX). ACh strongly inhibited the cGMP-evoked K current when applied at the plateau of the latter. 4-Phorbol 12,13-dibutyrate (PDBu) (1 M) rapidly and completely inhibited the cGMP response. It is concluded, that most of the results presented in this report contradict the hyothesis that cGMP is the intracellular mediator of ACh-induced changes in membrane conductance in the oocytes.Abbreviations ACh acetylcholine - cAMP cyclic adenosine 3,5-monophosphate - cGMP cyclic guanosine 3,5-monophosphate - EGTA ethylenediaminetetraacetic acid - Hepes N-2-hydroxyethyl-piperazinc-N-2-hydroxypropanesulphonic acid - IBMX 3-isobutyl-l-methylxanthine - IP₃ inositol 1,4,5-trisphosphate - PDBu 4-phorbol 12,13-dibutyrate     

Follicular density in ovarian biopsy of infertile women: a novel method to assess ovarian reserve

The ageing ovary appears to be characterized by depletion of primordial follicles. The relationship between infertility and the number of follicles in the ovarian cortex is not known. Moreover, there are no accurate markers or clinical methods to predict the decline in ovarian reserve. This study investigates the correlation between early follicular follicle stimulating hormone, ovarian size and follicular density in 60 infertile women aged 19-45 years (mean = 34.4 +/- 5.5). An ovarian biopsy was taken from each patient while performing diagnostic laparoscopy (n = 28) or laparotomy for tubal surgery or myomectomy (n = 32). The median number of follicles was similar in tubal and unexplained infertility patients (9.5 versus 5.5). Increasing age showed a significant negative correlation with follicular density and ovarian volume (r = -0.46, P = 0.0003;. r = -0.43, P = 0.0016, respectively). In women > or = 35 years of age the ovarian volume showed a strong correlation with follicular density (r = 0.71, P < 0.0001). Our results indicate that infertile women in their late thirties and over have a decreased ovarian reserve which could possibly be predicted by ovarian volume measurement. Ovarian biopsy may have a place as part of infertility evaluation in older women.      

Pseudotumors in Small-Head Metal-on-Metal Total Hip Arthroplasties at a Minimum Follow-Up of 20 Years

BackgroundMetal-on-metal (MOM) surfaces in total hip arthroplasty (THA) have been used widely. Serum cobalt and chromium levels have been the standard investigation for follow-up examinations, but magnetic resonance imaging (MRI) with metal artifact reducing sequences has shown good results in detecting pseudotumors. The aim of this study is to survey a significant correlation among MRI findings, serum metal levels, and clinical scores in patients with small-head MOM implants and if serum cobalt and chromium levels are sufficient in detecting patients with pseudotumors in the long-term follow-up.MethodsAt a minimum follow-up of 20 years, 26 patients (29 THAs) of the original 98 patients (105 THAs) included in this study between November 1992 and May 1994 were available for follow-up examination. Clinical scores, serum metal ion levels, and MRIs were obtained.ResultsWe found mean serum cobalt levels of 1.87 μg/L (±3.44) and chromium levels of 2.23 μg/L (±2.96) and very good clinical and functional results (mean Harris Hip Score 88.6) in the long-term follow-up. Pseudotumors were detected in MRIs of 21 hips. There were no significant differences between patients with or without pseudotumors regarding serum metal levels and the correlation for clinical outcome scores, demographic data, and cup inclination. The cumulative rate of survival was still at 91.4% at 22.8 years.ConclusionThis study presents the first published data on small-head MOM hips, comparing metal ion levels, pseudotumors, clinical, and radiological results in a follow-up period of more than 20 years and reveals that serum metal levels are not significantly higher in patients with pseudotumors.Level of EvidenceTherapeutic Level III