The effects of co-culture with human fibroblasts on human embryo development in vitro and implantation

In a human in-vitro fertilization (IVF) programme, the effect of co- culture of embryos with human fibroblasts was evaluated with respect to pregnancy rate and embryo development. Patients were included in the study after giving informed written consent. The IVF treatments were randomly assigned by stratification of both age (<36 versus > or =36 years) and previous IVF attempts (yes versus no). After fertilization was established, the zygotes were transferred to a 4-well dish with or without fibroblasts and cultured for 2 days. On the third day after ovum pick-up (OPU), cell number and quality [5 (good) to 1 (poor)] of the embryos were scored and a maximum of three embryos was transferred. Supernumerary embryos of good quality were cryopreserved. The design of this study was a group sequential trial with the objective of detecting differences between pregnancy rates following IVF with conventional incubation or incubation in co-culture with fibroblasts. This design included one evaluation at half-way data collection. In the study, 148 patients had an OPU, of whom 77 were allocated to the co-culture group. There was no statistically significant difference in pregnancy rate, cell number and embryo quality between the two groups. The ongoing pregnancy rate per embryo transfer was 27% in co-culture and 30% in the conventional culture group. The implantation rates per transferred embryo were 17 and 18% respectively. Using a multivariate logistic regression model for the probability of ongoing pregnancies, the odds ratio of co-culture, adjusted for age and previous IVF attempts, was not statistically significant. In conclusion, co-culture with human fibroblasts does not contribute to an improvement of embryo quality nor to a higher pregnancy rate after IVF in an unselected group of patients.      

The right to an heir in the era of assisted reproduction

The latest remarkable technological advances in assisted reproduction, which enable cryopreservation of spermatozoa, embryos and ovarian tissue, raise difficult and debatable legal, social, ethical and moral issues concerning the right to posthumous reproduction. Furthermore, reports on the attitudes of the general public and of centres licensed for infertility treatment in the United Kingdom found that the majority of women and centres support the idea of posthumous reproduction. In this paper we review the data published on this issue, and after considering the various aspects, we conclude that each case should be discussed and authorized by a multidisciplinary committee that includes physicians, clergy, psychiatrists, psychologists, sociologists and other appropriate parties. In our opinion, the main principles that should guide this committee would allow posthumous reproduction in the context of marriage when a prior consent exists. For unmarried persons, post-mortem donation of gametes should be done only anonymously, if they are in agreement with existing laws concerning infertility treatments in every country and after appropriate consent and proper counselling. Moreover, any case which involves consanguinity or a possibility of incest should be forbidden, both for ethical and genetic reasons. In a case of pre-existing siblings, they should be consulted and their informed consent should be granted in advance so as to avoid legal problems in the inheritance of property.      

Blood supply of the olfactory nerve

Summary The authors report the results of a series of dissections and anatomic sections of the fronto-basal region of the brain and of the anterior cranial fossa in human cadavers. The constant presence of an arachnoidal cistern above the olfactory nerve was verified. The arachnoid separates from the pial membrane and forms a bridge with the ventral part of the olfactory bulb and tract, from the lateral edge of the olfactory sulcus to the medial edge of the gyrus rectus. The cistern is wide in its anterior portion, between the gyrus rectus and the olfactory bulb, and is reduced to a virtual slit in its posterior portion where the tract is lodged in the olfactory sulcus. The olfactory nerve can be separated without damaging fronto-basal arachnoidial adhesions over several centimeters. Dissection of this region after intravascular injection of colored media shows the constant presence of an artery destined to the olfactory bulb and tract. It originates either from the lateral surface of the anterior cerebral a. (segment A2), or from the medial fronto-basal a., and consistently provides terminal branches in front of the olfactory trigone in the medial olfactory sulcus. At their ventral extremity, the olfactory structures are therefore vascularised independently for several centimeters, from the lower face of the frontal lobe. The independent vascularisation of the olfactory nerve, the tenuous and easily detachable adhesions, and the actual presence of a true arachnoidal cistern all contribute to enabling surgical techniques which conserve olfactory function during anterior approaches.

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Vascularisation du nerf olfactif. Rapports méningés et applications chirurgicales

Résumé Les auteurs rapportent les résultats d'une série de dissections et de coupes de la région fronto-basale de l'encéphale et de la fosse crânienne antérieure sur sujets cadavériques. La présence constante d'une citerne arachnoïdienne au dessus du n. olfactif a été vérifiée. L'arachnoïde se sépare du feuillet pial et passe en pont à la partie ventrale du bulbe et du tractus olfactifs, du bord latéral du sillon olfactif au bord médial du gyrus rectus. La citerne est large dans sa portion antérieure, entre le gyrus rectus et le bulbe olfactif, se réduit à une fente virtuelle postérieure lorsque le tractus se loge dans le sillon olfactif. Le n. olfactif peut être séparé sans dommage des adhérences arachnoïdiennes fronto-basales sur quelques centimètres. La dissection de cette région, après injection intravasculaire de masses colorées montre, de façon originale, la présence constante d'une artère destinée au tractus et au bulbe olfactifs. Elle naît soit de la face latérale de l'a. cérébrale antérieure (segment A2), soit de l'a. fronto-basale médiale, pour donner ses branches terminales toujours en avant du trigone olfactif dans le sillon orbitaire médial. Sur quelques centimètres à leur extrémité ventrale, les structures olfactives ont donc une vascularisation indépendante de la face inférieure du lobe frontal. L'indépendance vasculaire du n. olfactif, des adhérences ténues, facilement détachables, et la réalité vérifiée d'une véritable citerne arachnoïdienne permettent d'imaginer des techniques conservatrices de la fonction olfactive utilisées dans plusieurs indications de la chirurgie de la fosse crânienne antérieure.

     

Gene expression of connective tissue growth factor in adult mouse

The connective tissue growth factor (CTGF) is a well-known fibroblast mitogen and angiogenic factor that plays an important role in bone formation during embryogenesis. In the adult, CTGF is involved in wound healing as well as fibrotic and vascular disease. However, little is known about its physiological functions under non-pathological conditions in the adult organism. Here, we describe the cellular site of the CTGF mRNA expression in adult male and female mice as revealed by in situ hybridization histochemistry. Strong and persistent CTGF gene expression was particularly prominent in the mesenchyme of the cardiovascular system (aorta, auricular tissue, renal glomeruli), the mesenchyme surrounding the ovarian follicles or the testicular tubes in the gonadal tissue, and the subcapsular mesenchyme bordering densely innervated parts of whisker hair vibrissae. CTGF hybridization signals were not observed in the mesenchyme of many other organs including gut, muscle, liver or most parts of the lymphatic tissue. Strong expression was also present in the primary (early) ovarian follicles, the epithelium of the deep uterine glands and on myenteric ganglia neurons. These data suggest a selective and continuous mesenchymal function in the gonads and those tissues attracting very strong vascular supply or peripheral innervation. CTGF may also be involved in the cyclical proliferation of the uterine gland epithelium and in the early stages of follicular maturation, as well as in the neuropeptide regulation in the gut, cardiovascular and renal systems.     

Structure-activity relationships and effects of platelet-activating factor antagonists in the hetrazepine series

Thieno-triazolo-1,4-diazepines (hetrazepines) antagonize platelet-activating factor (PAF) induced platelet aggregation and inhibit the binding of [3H]-PAF. Introduction of a carboxamide alkyl side chain into the thiophene ring leads to compounds with less affinity to the benzodiazepine receptor and without sedative effects on the central nervous system (e.g., WEB 2086). By ring closure of the side chain, new tetracyclic compounds have been obtained. A parabolic relationship between either [3H]-PAF binding or PAF activity and the bulkiness of the alkyl substituents to the triazolo ring of the hetrazepines or of the bulkiness the 2-acyl moiety of the PAF analogues was found in quantitative structure-activity relationships. This suggests that perhaps the alkyl substituent of the hetrazepines fits the same receptor pocket as the 2-acyl moiety of the PAF agonists.     

The time course of cross-talk during the simultaneous specification of bimanual movement amplitudes

 We investigated the time course of the amplitude specification of rapid bimanual reversal movements (lateral displacements on two digitizers). To this end we used the timed-response paradigm in which the response has to be initiated synchronously with an auditory signal. Information about the required amplitudes was presented at various times before the synchronization signal. Consistent with previous results, the progression of amplitude specification was reflected in the dependence of the amplitudes of the reversal movements on the time interval between amplitude information and synchronization signal. Same or different amplitudes for the hands were used to examine cross-talk at the programming level of the two-level model of intermanual interference. The results indicate the existence of cross-talk in particular at short intervals between information about amplitude and movement initiation. This is consistent with the notion that cross-talk between concurrent processes of amplitude specification is transient and vanishes as the time available for motor programming increases. Received: 28 August 1996 / Accepted: 10 July 1997     

Optic flow signals in extrastriate area MST: comparison of perceptual and neuronal sensitivity

The medial superior temporal area of extrastriate cortex (MST) contains signals selective for nonuniform patterns of motion often termed "optic flow." The presence of such tuning, however, does not necessarily imply involvement in perception. To quantify the relationship between these selective neuronal signals and the perception of optic flow, we designed a discrimination task that allowed us to simultaneously record neuronal and behavioral sensitivities to near-threshold optic flow stimuli tailored to MST cells' preferences. In this two-alternative forced-choice task, we controlled the salience of globally opposite patterns (e.g., expansion and contraction) by varying the coherence of the motion. Using these stimuli, we could both relate the sensitivity of neuronal signals in MST to the animal's behavioral sensitivity and also measure trial-by-trial correlation between neuronal signals and behavioral choices. Neurons in MST showed a wide range of sensitivities to these complex motion stimuli. Many neurons had sensitivities equal or superior to the monkey's threshold. On the other hand, trial-by-trial correlation between neuronal discharge and choice ("choice probability") was weak or nonexistent in our data. Together, these results lead us to conclude that MST contains sufficient information for threshold judgments of optic flow; however, the role of MST activity in optic flow discriminations may be less direct than in other visual motion tasks previously described by other laboratories.     

Antiarrhythmic effects of stirocainide in acute myocardial infarction

Ventricular arrhythmias, especially ventricular fibrillation, are assumed to be a main cause of sudden death during the first 24 h of acute myocardial infarction. Effective prophylaxis and acute suppression of these life-threatening rhythm disturbances are a major therapeutic problem. The present study was undertaken to investigate the efficacy of the new antiarrhythmic compound stirocainide (2-(1-benzylidene)cycloheptenimino-oxyethyl-diisopropylamine -2-butenedionate, Th 494) in suppressing "2nd phase arrhythmias" arising from large anteroseptal myocardial infarctions using a standardized experimental canine preparation. Our results demonstrate that "2nd phase arrhythmias"--i.e. frequent ventricular ectopics, tachycardias, salvos, and R-on-T phenomena--are reduced by 80-90% (sometimes even completely abolished) by stirocainide (dose: 4 mg/kg within 3 min, followed by 300 micrograms/kg X min over a 20-min period). The administration of the drug at the dose used does not produce severe cardiodepression, but intraventricular conduction time is significantly prolonged. Thus, Th 494 is a highly effective antiarrhythmic agent in acute myocardial infarction, and further experimental and clinical investigations on its antiarrhythmic and antifibrillatory properties may lead to beneficial therapeutic results.