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Luteinized unruptured follicle syndrome can explain female infertility. The precise mechanism by which the ovulatory follicle fails to rupture is unclear. The following case reports a pregnancy result in in vitro fertilization (IVF). The first stimulation, a long IVF protocol with low FSH dose, was successful. Different methods used for detection and treatment are discussed.

The ovary can be the target of an autoimmune disease involving many different autoantigens. The clinical feature of this disease often results in premature ovarian failure or infertility and may be either isolated or associated with other autoimmune pathologies, especially with adrenal autoimmunity. The diagnosis of an autoimmune mechanism relies on the presence of anti-ovarian antibodies, whose prevalence is quite variable according to the different methods used to detect them, and to the different stages of the disease. In addition, their clinical significance is not always clear, as to their pathologic or epiphenomenal nature. However, the study of these autoantibodies has led to the identification of some of their antigenic targets which have to be known for a better understanding of the pathologic mechanisms involved. This paper reviews anti-steroid producing cells, anti-gonadotrophin receptor, anti-gonadotrophin, anti-corpus luteum, anti-zona pellucida and anti-oocyte antibodies.

The diagnostic algorithms of ectopic pregnancy (EP) include sonographic procedures. Diagnostic sensitivity is low because the procedure is operator-dependent and each clinical aspect of EP is variable. We analyzed results of standardized ultrasound procedures performed within the framework of a detailed analysis of clinical findings.The sonographic procedure must be performed within the framework of an overall analysis including laboratory results (hCG level), examination of the decidua, localization of the corpus luteum, and careful detailed examination of adnexa. Hematosalpinx is pathognomonic of EP and is observed in 80% of cases. When diagnosis is doubtful, a second ultrasound procedure should be performed 48 hours later before undertaking laparoscopic diagnosis.The diagnostic sensitivity of ultrasonography has been consistently high in published series, undoubtedly because the studies were performed in referral centers highly experienced in diagnostic ultrasound.

Actions of the LH peak Mechanisms of the LH-peak triggered ovulation Interest of reproducing the LH peak in stimulated cycles

Luteinizing hormone (LH) is an hypophyseal glycoprotein involved in both follicular maturation and corpus luteum function. During the follicular phase, effects of LH must be considered according to the stages of follicular development: in the early follicular phase, LH acts through specific receptors, constitutively present on thecal cells, for stimulating androgen production. Androgens seem to be positively involved in the folliculogenesis in primates. Indeed, a positive correlation has been recently established between androgen receptor expression and follicular cell proliferation. Furthermore, androgens are active through a conversion to estrogens in granulosa cells. Estrogens are needed for achieving pregnancy. Thus, a question remains: what in the minimal amount of endogenous LH required for an optimal production of oestradiol? Several models have been investigated in clinical situations with hypogonadotrophic hypogonadism: WHO type I anovulation or GnRH analog-induced hypogonadisms. A large majority of these studies conclude that the minimal amount of LH needed during the follicular phase is probably low (1.5 IU/L of plasma LH level). Recent availability of GnRH antagonist will give a new opportunity for evaluating this minimal LH threshold. During the late follicular phase, LH plays a biphasic role, with a positive effect on steroidogenesis but a negative effect on cell proliferation. As suggested by S. Hillier, this negative effect on cell proliferation may be relevant to control the rate of follicular growth. One study, performed in WHO type I anovulatory patients, seems to confirm this assumption but further evaluation is needed to give support to this concept. Finally, LH is also involved in corpus luteum function. Due to the short half-life of LH as compared to hCG, the role of LH must be evaluated according to the adjunct therapies. For example, following a long-term GnRH aganist administration that constantly induces a profound hypophyseal desensitization, LH administration must be repeated to adequately sustain the corpus luteum function. This conclusion must be reconsidered with the recent introduction of GnRH antagonists. Indeed, according to their short-term effects on LH secretion, it may be presumed that a single injection of LH may be effective to maintain an adequate corpus luteum function.

The involvement of the uterus in early regression of corpora lutea induced by the ram effect was studied in seasonally anoestrous Barbarine ewes. In experiment 1, group I was only submitted to the male effect (control, n = 15) while group II (n = 14) was injected every 12 h with flunixin meglumine, a PGF2 alpha synthetase inhibitor (finadyne), from day 3 to day 6 (day 0: day of ram introduction). The preovulatory LH surge appeared at the same time (around 21 h after ram introduction) in both groups. Finadyne treatment significantly decreased 13-14-dihydro-15-keto-PGF2 alpha (PGFM) pulses (1.3 +/- 0.3 versus 0.4 +/- 0.2; P < 0.05), the number of short cycles (50 versus 14%, P < 0.05), and provided a single peak of oestrus, 15-16 days after the introduction of the rams, instead of between day 14 and day 23 (P < 0.01). In experiment 2, 17 hysterectomized ewes were allocated into two groups: group III (n = 8) was injected with oil and group IV (n = 9) received an intramuscular injection of 20 mg of progesterone immediately before introduction of rams. An additional group of intact ewes was used as control (group V, n = 9). Hysterectomy did not affect the ovulation response to the ram effect, but completely suppressed short cycles (0 versus 78%, P < 0.001). The preovulatory LH surge was delayed in hysterectomized females (36.0 +/- 14.1 versus 16.6 +/- 11.4 h; P < 0.004). Treatment with progesterone significantly (P < 0.01) increased the interval between introduction of rams and the preovulatory LH surge. In conclusion, suppression of short cycles by hysterectomy and an inhibitor of PGF2 alpha synthetase suggest that the uterus is essential for determining the lifespan of ram-induced corpora lutea and that premature release of PGF2 alpha is the cause of early luteal regression. The hypothesis that lower secretion of progesterone before D5 could be the initial cause of the premature induction of the luteolytic signal is discussed.

Because of the anatomical position of the Corpus luteum within the ovary, rectal palpation is of little value for identification and evaluation. The aim of this review is to familiarize the practitioner with the echographic examination of the Cl. He should be able to recognize different stages of this important structure and to correlate ovulation and the existence of the Cl. Various specific criteria and details regarding equine echography are reported and illustrated, using the the most recently published scientific data.

It was found previously that the reduction of ovarian oxytocin (OT) content by up to 80% on d 12 and 16 of the cycle affects neither luteolysis nor estrous cycle duration in cattle. Because ovarian OT is suggested to be involved in progesterone synthesis/secretion, in the present study we wanted to investigate whether ovary depletion of OT in the early stages of the estrous cycle will influence the corpus luteum (CL) secretory function. In experiment 1, heifers (n = 15) had cannulae inserted into the aorta abdominalis through the coccygeal artery. The tip of each cannula was placed cranial to the origin of the ovarian artery. Noradrenaline (NA; 4 mg) was infused on d 5-10 for 30 min daily, evoking release of OT and lower, but evident, increases in the progesterone levels. This did not affect the length of the estrous cycle compared with control heifers infused with saline only. Because ovarian OT cannot be restored once discharged, NA served as a tool to deplete the CL of OT in experiment 2. The same dose of NA was given on d 5-10 to 4 heifers. The corpora lutea used to determine OT tissue concentrations were obtained by surgery under local anaesthesia 10-15 min after the last NA infusion. This dose of NA, depleted CL of OT by about 51% compared with control heifers. We conclude that significant reduction of ovarian OT content on d 5-10 does not affect the CL function. Thus, if ovarian OT is involved in ovarian steroidogenesis, it plays a modulatory rather than a mandatory role.

Studies on human ovary embryogenesis and adult post-ovulatory surgically resected ovaries allowed the authors to propose a new conception on the genesis of corpus luteum: large luteal cells would be derived from theca interna cells and small luteal cells would come from externa theca cells. So there would be a structural unity of luteal tissue which might explain steroidogenesis potential of these two types of cells, derived both from the same ovarian stroma. On the other hand if granulosa cells played an important function in bio-conversion of androgens to oestradiol by aromatase activity before ovulation, their role is over after the expulsion of the oocyte out of the follicle; derived from primitive sex cords of coelomic mesothelium origin, granulosa cells act to support and surround the oocyte; they disappeared at the disappearance of the oocyte from the follicle.

This experiment was conducted in 59 Lacaune breed ewes in order to compare milk production and milk distribution between alveolar and cisternal storage after superovulation. After a corpora lutea (CL)-free control period, the ewes were superovulated by different treatments (experimental period) and 5 classes were differentiated according to the number of corpora lutea observed (0, 1, 2, 3 to 6 and6 CL respectively (group A (n = 20), B (n = 7), C (n = 14), D (n = 7), E (n = 11)). Our results showed a positive correlation between the number of corpora lutea and the oxytocin and progesterone levels in plasma, total milk production and cisternal volume, and a negative correlation with alveolar volume. The milk production at the evening milking for groups A and E (388.6 and 384.8 ml respectively during the control period) respectively reached 321.7 ml (-17.2%) and 413.4 ml (+7.4%) during the experimental period; ie, a 24.6% difference between these 2 extreme groups. These results could likely be explained by oxytocin levels reaching those obtained during milking and by the effect of milk transfer from the alveolar to the cisternal lumen. Additionally, progesterone could act directly on milk synthesis at the level of the secretory cells.

The authors present a histological study of the formation of the corpus luteum after follicular rupture. According to the classical conception, the corpus luteum is derived from luteinisation of the granulosa cells: the theca interna participates in its formation only to a lesser degree. The authors criticize this histogenesis and describe the corpus luteum as being entirely derived from thecal cells. Large and small luteal cells are all derived from mesenchymal elements of the ovarian stroma, which are the precursors of steroid-secreting cells. According to the authors, granulosa cells derived from the primary sex cords of coelomic mesothelial origin only play a support role for the oocyte. After expulsion of the oocyte from the dominant follicle, the granulosa cells which remain in the follicular cavity disappear without a trace.

This experiment was conducted in 59 Lacaune breed ewes in order to compare milk production and milk distribution between alveolar and cisternal storage after superovulation. After a corpora lutea (CL)-free control period, the ewes were superovulated by different treatments (experimental period) and 5 classes were differentiated according to the number of corpora lutea observed (0, 1, 2, 3 to 6 and > 6 CL respectively (group A (n = 20), B (n = 7), C (n = 14), D (n = 7), E (n = 11)). Our results showed a positive correlation between the number of corpora lutea and the oxytocin and progesterone levels in plasma, total milk production and cisternal volume, and a negative correlation with alveolar volume. The milk production at the evening milking for groups A and E (388.6 and 384.8 ml respectively during the control period) respectively reached 321.7 ml (-17.2%) and 413.4 ml (+7.4%) during the experimental period; ie, a 24.6% difference between these 2 extreme groups. These results could likely be explained by oxytocin levels reaching those obtained during milking and by the effect of milk transfer from the alveolar to the cisternal lumen. Additionally, progesterone could act directly on milk synthesis at the level of the secretory cells.

In a young woman, hemiperitoin is nearly always the result of the rupture of an ectopic pregnancy. The authors report the case of the rupture of a cyst of a corpus luteum and they review the literature in order to identify the semiological signs and it highlight the difficulty of reaching a diagnosis by non-invasive methods. The treatment remains surgery, involving ablation of the corpus luteum.

The diagnosis of pregnancy described in this article is based on the observation of milk ejection which, in the case of corpus luteum maintenance, results from the release of luteal oxytocin induced by intravenous administration of a non luteolytic dose of PGF2 alpha. The tests were performed in 410 lactating cows, 18-22 days after insemination (mean 19.95 days, SD 0.75), 3 h prior to the evening milking. A cannula was placed in the left fore-teat; when the cisternal milk flow ceased, a small dose of a prostaglandin F2 alpha analogue (256 micrograms Dinolytic) was injected. If a corpus luteum was present, the alveolar milk flow (1,276 +/- 570 ml) started 86 +/- 35 s later and pregnancy could be presumed. If the corpus luteum was no longer functional, the milk flow did not start again and the cow was considered not pregnant. The accuracy of positive results, ie 72.3%, significantly exceeded that obtained by radioimmunoassay of plasma progesterone used as a reference method, ie 68.6% (P less than 0.05). By contrast, the accuracy of negative results was lower, ie 93.5 vs 100%, (P less than 0.05): of the 195 pregnant cows which proceeded to term, 10 did not respond to the milk ejection test. In spite of these reserves, the test has the advantage of being inexpensive, rapid (about 5 min) and easy to interpret, ie either the milk flows or it does not. In addition, it may be used early, because from day 20 after Al the reliability of prediction of non pregnant cows (67.0%) was significantly higher when compared to the use of progesterone radioimmunoassay (58.6%) (P less than 0.05). With such a test, non pregnant cows can be reinseminated immediately and not only after a 3-week period. This may contribute to reducing the length of the infertile period.

The diagnosis of pregnancy described in this article is based on the observation of milk ejection which, in the case of corpus luteum maintenance, results from the release of luteal oxytocin induced by intravenous administration of a non luteolytic dose of PGF2 alpha. The tests were performed in 410 lactating cows, 18-22 days after insemination (mean 19.95 days, SD 0.75), 3 h prior to the evening milking. A cannula was placed in the left fore-teat; when the cisternal milk flow ceased, a small dose of a prostaglandin F2 alpha analogue (256 micrograms Dinolytic) was injected. If a corpus luteum was present, the alveolar milk flow (1,276 +/- 570 ml) started 86 +/- 35 s later and pregnancy could be presumed. If the corpus luteum was no longer functional, the milk flow did not start again and the cow was considered not pregnant. The accuracy of positive results, ie 72.3%, significantly exceeded that obtained by radioimmunoassay of plasma progesterone used as a reference method, ie 68.6% (P less than 0.05). By contrast, the accuracy of negative results was lower, ie 93.5 vs 100%, (P less than 0.05): of the 195 pregnant cows which proceeded to term, 10 did not respond to the milk ejection test. In spite of these reserves, the test has the advantage of being inexpensive, rapid (about 5 min) and easy to interpret, ie either the milk flows or it does not. In addition, it may be used early, because from day 20 after Al the reliability of prediction of non pregnant cows (67.0%) was significantly higher when compared to the use of progesterone radioimmunoassay (58.6%) (P less than 0.05). With such a test, non pregnant cows can be reinseminated immediately and not only after a 3-week period. This may contribute to reducing the length of the infertile period.

The pulsatility of LH secretion has been known only since 1970. The pulsatility of progesterone secretion has now also been shown. The frequency and amplitude of these pulses vary during the three phases of the luteal period. The first or early luteal (EL) phase lasts four days starting from the peak of LH. There is no pulsatility of progesterone during EL. The frequency of LH pulsatility is 103 +/- 8 minutes. The second or mid luteal (ML) phases, from +6 to +9 days after the peak of LH, is characterised by pulses of LH and of progesterone, most often in positive crossover correlation and with 7 to 14 pulses per 24 hours. The frequency of LH pulsatility is 166 +/- 33 minutes according to Filicori. The amplitude of LH secretion is 4 to 40 ng/ml. The third or late luteal (LL) phase, occurring at +11 days before the menstrual period, has the same characteristics in terms of quality but shows variations in frequency and amplitude towards a decrease. Thus the amplitude of progesterone secretion is 2.8 to 9 ng/ml (Veldhuis). In the opinion of clinicians, the corpus luteum is independent up to LH+ 5 days. The injection of hCG during this time is ineffective. A single progesterone level is sufficient if the result is 10 ng/ml or more. The problem remains complex concerning results below 10 ng/ml. The solution suggested for the present is that described by Olive: during ML and/or LL, three samples in the morning at hourly intervals and two endometrial biopsies during two consecutive cycles.

Seven lactating Lacaune ewes underwent either a total luteectomy on day 19 of pregnancy (D19) (compensated from that stage by a daily progesterone supplementation of 25 mg to ensure embryonic survival; group 1:4 animals) or a control laparotomy (group 2: 3 animals). Intra-jugular injection of 200 micrograms of a synthetic PGF2 alpha analogue (Dinolytic, Upjohn) caused an increase in the intramammary pressure (IMP) and a concomitant rise in oxytocinaemia only in the presence of a corpus luteum, ie in all ewes of groups 1 and 2 before D19 and only in those of group 2 after that stage. These experiments confirm that the corpus luteum, and not the other ovarian compartments, releases oxytocin when prostaglandin F2 alpha is administered.

Lysine residues appear to play an important role in the biological activity of luteinizing hormone or lutropin (LH). Some derivatives obtained by chemical modification such as N-methylated LH exhibit the same hormonal activity than LH in the different steps of the mechanism of steroidogenesis. Some others, on the contrary, preserve the hormonal activity only at some steps. In this work was investigated the action of ovine LH and some derivatives on isolated cells prepared from ovine corpora lutea. Guanidinated LH (which is able to bind to LH receptors in Leydig cells but whose steroidogenic potency is very low) exhibits no binding or steroidogenic activity in the female (sheep or rat). As a consequence guanidyl LH can act as an inhibitor of LH action in the male (Leydig cells).

After the zona is shed, the ewe blastocyst increases rapidly in diameter and length. The aim of the present study was to examine the control of trophoblast growth. Twelve-day old ovine blastocysts, cut into pieces and cultured in vitro for 24 h, gave rise to structures called trophoblastic vesicles (blastocysts without the embryonic disc). Such trophoblastic vesicles (TV), cultured at least 5 to 10 days or more in vitro, were able to survive. However, they did not increase in length and only some of them began to form small buds. In contrast, after they were transferred surgically into the uterine horn ipsilateral to the corpus luteum on Day 12 of the oestrous cycle, these TV were elongated in 5 out of 7 recipient ewes slaughtered on Day 17. The structure of the TV was observed by scanning electron microscopy before and after in vitro elongation and then compared with that of control blastocysts which had been cultured or not. This study demonstrates that trophoblast elongation does not depend necessarily on the presence of the embryo proper, but can occur in TV composed only of the trophectoderm and the extraembryonic endoderm. The results also suggest that some unknown uterine factor(s) is involved in the development of trophoblastic tissue.

58 sterile women who had perfect biphasic temperature curves through their menstrual cycles were examined by laparoscopy in the luteal phase of the cycle. No pelvic lesion was found. In 21 patients it was seen that the follicle had not ruptured (the so-called non-ruptured follicle syndrome). In a further 9 cases there was no luteal follicle to be seen on the surface of the ovary. The respective values of the plasma biochemical parameters which reflect ovarian secretion in the luteal phase are discussed; the importance of oestrogen secretion at the 6th day of the luteal phase is emphasized. It has been shown that there are significant statistical differences in the levels of oestradiol in the blood.

The prostaglandins probably play an important role in the physiology of reproduction. In women as in men, they intervene at several levels. At the level of the ovary, the prostaglandins E may be modulators of the action of gonadostimulin on ovarian hormonogenesis, in close relationship with cyclic AMP and, furthermore, represent an important biochemical intermediate stage in the mechanism of ovulation. F2 prostaglandin, F2 alpha, on the other hand, represents in numerous animals, but not in women, a luteolytic factor of uterine origin. At the level of the hypothalamopituitary axis, E prostaglandins may modulate hypothalamic neuro-secretion and to a lesser degree, the liberation of pituitary stimulins, and thus intervene in gonadotropic function. At the level of the female genital tract, prostaglandins may influence uterine and tubal motility. It is perhaps by this latter effect that the very large quantities of seminal prostaglandin influence the process of fertilisation.

Badger luteal tissue fragments harvested and cultivated during the inactive phase do not resemble active corpus luteum as do granulosa cells in vitro. Production of oestrogen and progesterone by these fragments was examined. Amounts produced are much smaller than in the case of granulosa cells and are slightly influenced by the nature of the serum used in culture medium.

LH perfusion was performed on proestrus under pentobarbital anaesthesia in 4-days cyclic female Rats treated or not treated with FSH at the onset of estrous cycle. The number of follicles capable of undergoing luteinization was shown to be dependent upon the amount of LH available.

Corpora lutea from sheep and cows as well as human and primates contain both large and small steroidogenic cells exhibiting distinct functional properties. Only the small cells seem to be able to respond in vitro to LH stimulation by raising their progesterone secretion. However, the entire progesterone secretion of the corpus luteum has been shown to be regulated in vivo by LH in the primate. The LH steroidogenic action involves the activation of membrane adenylate cyclase whose molecular mechanism has been elucidated. Then a rise in intracellular cyclic AMP induces phosphorylation by a cyclic AMP dependent protein kinase of steroidogenic protein targets which have not yet been completely identified. In sheep and cows, luteolysis is believed to be the consequence of a series of reciprocal interactions between the corpus luteum whose large cells secrete pulses of oxytocin in response to PGF2 alpha luteolysin and the endometrium which secretes pulses of PGF2 alpha in response to oxytocin. The secretion of endometrial PGF2 alpha can only begin after the induction of endometrial receptors by estradiol, from the preovulatory follicles. Similarly in women and primates luteolysis, which does not require the presence of the uterus, could be the consequence of local reciprocal paracrine interactions between luteal cells of different types. These interactions are likely to involve PGF2 alpha' oxytocin and estradiol. The biochemical mechanism responsible for the inhibition by PGF alpha of LH induced progesterone secretion in luteal cells could involve a stimulation in the cell membrane of protein kinase C and the rise of cytosolic Ca+.(ABSTRACT TRUNCATED AT 250 WORDS)

The luteinizing action of oestradiol benzoate (OB) has been studied in 4-day cyclic female Wistar rats submitted to a dose of 10 mug on the morning of dioestrus I at 10-11 a.m. In a first experimental series a blockage of luteinization was observed in females injected with pentobarbital (PB) either on dioestrus I at 11 a.m. and 5 p.m. respectively or on dioestrus II at 1:30 p.m. In the second series the blockage of luteinization only occured in females injected with PB on dioestrus II at 1:30 p.m. Early mating during the night following dioestrus II overcame this action of PB. The luteinizing effects of OB were therefore concluded to be dependent on the activation on the afternoon of dioestrus II, of the nervous hypothalamic structures. They were also shown to depend on the sensitivity to PB and/or to OB, on the day of dioestrus I, of the hypothalamo-pituitary system.

The authors analyse the ultrasound aspects of normal and abnormal corpora lutea after reviewing the techniques for studying ovaries. The abnormalities include unruptured luteal follicles, cystic corpora lutea, haemorrhage into corpora lutea and ovarian hyperstimulation.

The amount of progesterone and estradiol secreted by human corpus luteum depends upon an adequate release of FSH and LH by pituitary gland during follicular phase and ovulation. In this paper, plasma determination of progesterone and estradiol were carried out in 109 women with benign breast disease during the luteal phase of their menstrual cycle. Results obtained were compared with those observed in 25 normal women studied in the same conditions. In women with benign breast disease, the curve of daily progesterone concentrations during luteal phase was lower than that of normal women. The progesterone peak at 5th day of luteal phase was only 8,1 +/- 3.8 ng/ml instead of 17.2 +/- 3.5 ng/ml in normal women. No significative difference was observed concerning plasma estradiol between patients and normal women. These results indicate that women with benign breast disease have an inadequate corpus luteum function which may be the result of disorder of ovulation. Pathophysiological implications resulting from this observation are discussed.

Despite the new techniques of biochemical evaluation of steroid hormones in the plasma and urines, the endometrial biopsy remains an easy valuable method of evaluation of ovarian activity. The clinical indications of the endometrial biopsy are mainly a history of sterility or an abnormal uterine bleeding if we exclude the diagnosis of cancer. Different technical procedures should be followed carefully in order to get a valuable answer. The biopsy should be taken at the right time of the cycle which means 10 to 12 days after ovulation. The danger of interrupting a pregnancy is minimal but in a case of sterility, the biopsy can be performed 4 to 6 days after ovulation to prevent any interference with a early pregnancy. Proper fixation, embedding and staining must be the rule. A fragment of the middle layer of the functionalis must be present to evaluate accurately the hormonal stimulation. Isthmic or cervical tissues are unsuited for functional diagnosis. The existence of an endometritis or the administration of steroid hormones are clinical circumstances which prevent any functional evaluation. The normal menstrual cycle can be divided into different functional phases: the early, the middle and the late proliferative phases, and the early and late secretory phases followed by the menstruation period. The different cellular components of the endometrial mucosa will exhibit various changes corresponding to each of the phases. The interpretation of the endometrial biopsy lies in the correlation between the observed image and the image corresponding to that date of the cycle. The functional disturbances are associated with absent, deficient or excessive function of the ovarian hormonal secretion. The endometrial mucosa will reflect these anomalies revealing atrophic, hypoplastic or hyperplastic conditions of the glandular and stromal components. It is essential to obtain the clinical informations including the knowledge of any hormone administration to provide a valuable diagnosis. Properly interpreted, the endometrial biopsy remains a very useful technique in the study of hormonal ovarian disturbances.

The diffusion and uptake of two benzacridines with very similar chemical structures, but with different carcinogenic powers were investigated at the level of various organs and at the cellular level in the female rat. The chronology of the processes and lesions observed was different according to the respective carcinogenic power of the two benzacridines. On account of the small doses used, only necrotic lesions were observed, mainly in the liver and adrenal glands, but no tumorous lesions were observed. Uptake of fluorescent substance at the level of the nuclei of certain cells (submaxillaris, liver, pancreas, adrenal glands) was noticed as in previous experiments; this transient process appeared about the 100th day and lasted fairly long according to the form of benzacridine and the organ.