Bruxism and oral parafunctional hyperactivity in social phobia outpatients.

Anxiety and selective serotonin reuptake inhibitors (SSRIs) are considered aggravating factors for bruxism. We examined the influence of anxiety, depression and SSRI on bruxism in social phobia (SP). Twenty-three drug naïve, 17 SSRI-treated SP patients and 33 healthy controls underwent a psychiatric assessment and completed Leibowitz Social Anxiety Scale and Beck Depression Inventory. Oral parafunctional activity (PF) was evaluated by TM-dental examination and by a questionnaire. Drug- naïve and SSRI-treated SP patients did not differ on demographic and clinical measures. Awake bruxism, 'JAW PLAY' and at least one PF were more prevalent in SP than in controls. Severity of SP predicted the presence of PF. SP, but not depression, was associated with higher risk of oral PF and awake bruxism. Chronic SSRI treatment of SP did not affect sleep and awake bruxism. Dental and anxiety screening may improve the prognosis psychiatric and dental patients. Effective treatment of SP may mitigate bruxism.

Specificity of expression of the muscle and brain dystrophin gene promoters in muscle and brain cells.

The gene that is defective in Duchenne and Becker muscular dystrophies is expressed in the muscle and brain. However, the 5' ends of the 14 kb mRNA in these tissues are derived from two different exons, indicating the involvement of at least two promoters in the regulation of the cell-type and developmental specificities of expression of this gene. In the study presented here, we used the polymerase chain reaction and RNAase protection methods and various cell cultures to investigate the specificities of expression of these promoters. The results indicate a very stringent control of expression of the two promoters. In cloned rat myogenic cells, only the muscle-type dystrophin transcript was detected, and its presence was correlated with the formation of multinucleated fibers. In neuronal cell cultures, the brain-type transcript was detected. However, glial cell cultures expressed the muscle transcript only. Some cell lines derived from brain cells expressed both isoforms.

[Crestal core elevation technique--case series and literature review].

Sinus floor augmentation is the most common surgical procedure for gaining bone volume in the posterior maxilla. The purpose of this procedure is to enable implant placement un edentulous ridges. The most common techniques for sinus augmentation are: 1. Bone added osteotome sinus floor elevation (BAOSFE). 2. Crestal core elevation (CCE). 3. Lateral window technique (LWT). Since the early 80's many articles describing the successful use of different augmentation materials for sinus elevation have been published. Although many articles have been published on the lateral window technique and the osteotome technique as described by Summers, few articles have been published on the crestsal core sinus elevation technique. This technique, first described by Summers, includes the use of wide diameter osteotomes and trephine bur with a diameter of 6 m"m. This technique is implemented in situations when the available bone for implant placement is less than 6 m"m , which impairs the possibility of achieving primary stability of the implant. In those cases crestal core elevation is performed and implant placement is postponed 3-8 months later. Modification of the technique described by Summers was published by Fugazzoto, this technique is implemented concomitant with the extraction of the upper molars. The crestal core elevation technique (CCE), which is based on the BAOSFE (Bone Added Osteotome Sinus Floor Elevation), is based on the principle of hydraulic force acting on fluids and particles which transfer the vector of force to all direction, in this case the sinus membrane. The detached core of interradicular bone prior to osteotome placement and malleting significantly reduces surgical trauma to the patient especially in cases where a significant portion of the pre-disease interradicular bone remains. The concomitant placement of particulate material and a membrane at the time of tooth extraction offers the advantage of minimizing if not eliminating significant 3-dimensional alveolar resorption. In this article 3 cases treated using the crestal core elevation technique are presented. Advantages and disadvantages of the technique and indication for use will be discussed.

[Alveolar ridge augmentation with hip corticocancellous allogenic block graft prior to implant placement].

The use of autogenous block bone grafts in bone regeneration procedures for alveolar ridge augmentation can be limited by donor-site morbidity and complications. In this study, allogeneic block grafts were used for ridge augmentation prior to implant placement. Thirty six patients with severe ridge width and height deficiency underwent augmentation using an allogeneic corticocancellous iliac block bone graft. After rigid fixation of the graft, the site was covered with a freeze dried allogeneic dura mater membrane or restorable collagen membrane and then tension-free closure was performed. Implants were placed three to four months after surgery. Three to six months after implant placement, panoramic radiographs were taken and implants were uncovered for prosthetic restoration. Out of the 70 implants placed, one implant failed to integrate. Out of the 49 grafts placed one graft showed three millimeters of bone resorbtion at the superior buccal aspect of the graft. No other clinical problems were observed. The block grafts were clinically well integrated into the recipient site. The augmented bone remained stable throughout implant placement procedures. Clinical outcome evidence demonstrates that allogeneic block bone grafts in conjunction with G.B.R principles might be a viable alternative to autogenous grafts in selected patients with alveolar ridge deficiencies.

[Full arch impression techniques utilizing addition type poly vinyl siloxane for fabrication of tooth born fixed partial dentures].

A precise impression is necessary for fabricating an accurately fitting cast restoration. For this purpose, Polyvinyl Siloxane (PVS) impression materials are extremely popular because of their combination of excellent physical properties, handling characteristics and dimensional stability. Its excellent clinical features remain unaffected if simple measures are guarded. This review presents several impression techniques using PVS and recommends the one that provides the most accurate impression, utilizing the superior qualities of the PVS. The one step impression technique where no control of wash bulk and thickness exists, is considered to be the least accurate impression method with measured discrepancies as large as 7 times the original inter preparation distance and 40 times the original cross arch dimensions. Furthermore, the direct contact between the less refined putty material and the tooth preparation, as well as the high prevalence of air bubble entrapment, seriously compromises restoration longevity. The two stage impression technique has proved to produce the most accurate and reliable impressions due to complete control of the wash bulk and thickness entailed. The ideal wash bulk thickness should range between 1 to 2.5 mm all around the abutment tooth in order to minimize distortion of its subsequent die. Using a "Putty Tray" at the first stage with a predetermined space encircling the abutments will allow the wash to flow to its ideal uniform bulk size at the second stage. A uniform bulk size will prevent differential setting contraction and uneven changes at the dimensions of the die. The easiest and most clinically applicable method to achieve the desired space around the preparations is by loading the Putty material with the temporary crowns in place, followed by their removal at the second stage and occupation of the created space by the wash. In general, less control of wash bulk will result in either insufficient or excessive wash material which will determine uneven dimensional changes in the impression. This, in turn, will produce ill fitting cast restoration.

PreImplantation Factor (PIF*) endogenously prevents preeclampsia: Promotes trophoblast invasion and reduces oxidative stress.

Preeclampsia is a unique pregnancy disorder whose patho-physiology is initiated early in gestation, while clinical manifestations typically occur in mid-to-late pregnancy. Thus, prevention should optimally be initiated in early gestation. The intimate interaction between PIF, secreted early by viable embryos, and its host-mother provides insight into putative mechanisms of preeclampsia prevention. PIF is instrumental at the two critical events underlying preeclampsia. At first, shallow implantation leads to impaired placentation, oxidative stress, protein misfolding, and endothelial dysfunction. Later in gestation, hyper-oxygenation due to overflow of maternally derived oxygenated blood compromises the placenta. The first is likely involved in early preeclampsia occurrence due to reduced effectiveness of trophoblast/uterus interaction. The latter is observed with later-onset preeclampsia, caused by a breakdown in placental blood flow regulation. We reported that 1. PIF promotes implantation, endometrium receptivity, trophoblast invasion and increases pro-tolerance trophoblastic HLA-G expression and, 2. PIF protects against oxidative stress and protein misfolding, interacting with specific targets in embryo, 3. PIF regulates systemic immunity to reduce oxidative stress. Using PIF as an early preventative preeclampsia intervention could ameliorate or even prevent the disease, whose current main solution is early delivery.

Response of human ovarian carcinoma cell lines to antiprogestin mifepristone.

The effects of antiprogestin mifepristone (MF) on the growth, progesterone receptor expression and cell cycle kinetics of several human ovarian epithelial carcinoma (OEC) cell lines were evaluated. MF, a synthetic antiprogestin, has been shown to have some antiproliferative activity in breast tumors and in the endometrium, but its efficacy in ovarian carcinomas has not been explored previously. Continuous exposure of OEC cells to MF resulted in a dose- and time-dependent growth inhibition, as determined by MTT assay. Growth inhibition was apparent by day three following addition of MF to cultures in vitro. All cell lines used in this study expressed a progesterone receptor (PR). MF down regulated PR expression on these cells. Changes in the cell cycle kinetics of OEC cells exposed to MF correlated with the observed antiproliferative effects. MF blocked cells in a G0/G1 phase of the cell cycle and thus reduced the number of cells in the S phase. The efficacy of MF was compared with that of taxol and tamoxifen in the same human OEC cell lines. Continuous exposure of OEC cells to tamoxifen resulted in a varied cytostatic response and a transient change in the cell cycle. Taxol inhibited growth of some but not all of the cell lines. These results indicate that PR-positive human OEC cells are sensitive to MF in vitro and that MF may be an active agent against ovarian epithelial tumors.

1,25-Dihydroxyvitamin D3 enhances cytosolic free calcium in HL-60 cells.

1,25-Dihydroxyvitamin D3 (1,25[OH]2D3) caused a rise in the concentration of intracellular free calcium ions ([Ca2+]i) in HL-60 cells. This effect of 1,25(OH)2D3 parallels its suppression of cell proliferation and its induction of cell differentiation into monocyte-like cells. The changes in [Ca2+]i are dose and time dependent. The concentration of 1,25(OH)2D3 (10(-7) M) that induced maximal differentiation also caused the maximal increase in intracellular Ca2+. The rise in cytoplasmic free Ca2+ concentration was not immediate and reached statistical significance only after 24 h. The [Ca2+]i reached its peak at 48 h (134 +/- 4 nM vs 101 +/- 3 nM in controls) and remained stable at this level. The increase in intracellular Ca2+ was found to be related to new protein synthesis, because it was inhibited in the presence of specific RNA and protein synthesis inhibitors. The rise in [Ca2+]i was not observed during incubation of HL-60 cells with 24,25-dihydroxyvitamin D3 (24,25[OH]2D3), a vitamin D metabolite that does not induce the differentiation of HL-60 cells. In contrast, 25-hydroxyvitamin D3 (25-OH-D3) and phorbol 12-myristate 13-acetate (TPA), both of which induce differentiation in this cell line, also increase [Ca2+]i. In conclusion, the present study emphasizes that a significant increase in intracellular free Ca2+ occurs in the effect of 1,25(OH)2D3 on HL-60 cells.

The involvement of calcium ions in the effect of 1,25-dihydroxyvitamin D3 on HL-60 cells.

1,25-Dihydroxyvitamin D3 (1,25[OH]2D3) was found to suppress growth of human leukemic cells (HL-60), and to induce the differentiation of these cells to monocyte-like cells. The purpose of the present study was to examine the role of calcium ions in the effects of 1,25(OH)2D3 on HL-60 cells. Incubation of the HL-60 cells with 1,25(OH)2D3 (10(-7) M) for 4 days caused a significant inhibition of 50% of cell growth. The number of differentiated cells increased simultaneously from 24 x 10(3) +/- 2 x 10(3) in the controls to 658 x 10(3) +/- 32 x 10(3) in the 1,25(OH)2D3 (10(-7) M)-treated cells. The role of calcium ions in the effects of 1,25(OH)2D3 on HL-60 cells was first studied by changing the available calcium in the medium and by measuring the effect of 1,25(OH)2D3 on intracellular Ca2+ levels. Limitation of the available Ca2+ by means of ethyleneglycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) or verapamil enhanced the inhibitory effect on proliferation and decreased the number of differentiated cells obtained by 1,25(OH)2D3 alone. These effects could be abolished by restoring the Ca2+ levels. The role of the intracellular free Ca2+ ions in the effect of 1,25(OH)2D3 was further illustrated by measuring the intracellular Ca2+ levels. The intracellular free Ca2+ concentration in 1,25(OH)2D3 (10(-7) M)-treated HL-60 cells rose significantly from 117.0 +/- 6.3 nM in the untreated HL-60 cells to 145.0 +/- 7.5 nM in the treated cells (p less than 0.02). Addition of verapamil moderated the increase in intracellular free Ca2+ (125.0 +/- 5.2 nM) obtained by 1,25(OH)2D3 alone. Thus the elevation of intracellular free Ca2+ caused by 1,25(OH)2D3 treatment may be involved in the effect of the hormone on the HL-60 cells.

Immune regulatory and neuroprotective properties of preimplantation factor: From newborn to adult.

Embryonic-maternal interaction from the earliest stages of gestation has a key, sustained role in neurologic development, persisting into adulthood. Early adverse events may be detrimental in adulthood. Protective factors present during gestation could significantly impact post-natal therapy. The role of PreImplantation Factor (PIF) within this context is herein examined. Secreted by viable early embryos, PIF establishes effective embryonic-maternal communication and exerts essential trophic and protective roles by reducing oxidative stress and protein misfolding and by blunting the nocive let-7 microRNA related pathway. PIF's effects on systemic immunity lead to comprehensive immune modulation, not immune suppression. We examine PIF's role in protecting embryos from adverse maternal environment, which can lead to neurological disorders that may only manifest post-nataly: Synthetic PIF successfully translates endogenous PIF features in both pregnant and non-pregnant clinically relevant models. Specifically PIF has neuroprotective effects in neonatal prematurity. In adult relapsing-remitting neuroinflammation, PIF reverses advanced paralysis while promoting neurogenesis. PIF reversed Mycobacterium smegmatis induced brain infection. In graft-vs.-host disease, PIF reduced skin ulceration, liver inflammation and colon ulceration while maintaining beneficial anti-cancer, graft-vs.-leukemia effect. Clinical-grade PIF has high-safety profile even at supraphysiological doses. The FDA awarded Fast-Track designation, and university-sponsored clinical trials for autoimmune disorder are ongoing. Altogether, PIF properties point to its determining regulatory role in immunity, inflammation and transplant acceptance. Specific plans for using PIF for the treatment of complex neurological disorders (ie. traumatic brain injury, progressive paralysis), including neuroprotection from newborn to adult, are presented.

PreImplantation Factor bolsters neuroprotection via modulating Protein Kinase A and Protein Kinase C signaling.

A synthetic peptide (sPIF) analogous to the mammalian embryo-derived PreImplantation Factor (PIF) enables neuroprotection in rodent models of experimental autoimmune encephalomyelitis and perinatal brain injury. The protective effects have been attributed, in part, to sPIF's ability to inhibit the biogenesis of microRNA let-7, which is released from injured cells during central nervous system (CNS) damage and induces neuronal death. Here, we uncover another novel mechanism of sPIF-mediated neuroprotection. Using a clinically relevant rat newborn brain injury model, we demonstrate that sPIF, when subcutaneously administrated, is able to reduce cell death, reverse neuronal loss and restore proper cortical architecture. We show, both in vivo and in vitro, that sPIF activates cyclic AMP dependent protein kinase (PKA) and calcium-dependent protein kinase (PKC) signaling, leading to increased phosphorylation of major neuroprotective substrates GAP-43, BAD and CREB. Phosphorylated CREB in turn facilitates expression of Gap43, Bdnf and Bcl2 known to have important roles in regulating neuronal growth, survival and remodeling. As is the case in sPIF-mediated let-7 repression, we provide evidence that sPIF-mediated PKA/PKC activation is dependent on TLR4 expression. Thus, we propose that sPIF imparts neuroprotection via multiple mechanisms at multiple levels downstream of TLR4. Given the recent FDA fast-track approval of sPIF for clinical trials, its potential clinical application for treating other CNS diseases can be envisioned.

Spontaneous, gonadotropin-releasing hormone-induced, and progesterone-inhibited pulsatile secretion of human chorionic gonadotropin in the first trimester placenta in vitro.

Using a multichannel superfusion apparatus, the secretion of human chorionic gonadotropin (hCG) was measured at 1-6 minute intervals in placental explants at 7-9 weeks of gestation. hCG was found to be secreted in distinct pulses (4-5 fold above baseline) every 11-23 minutes peak to peak. Addition of one minute pulses of GnRH analog significantly increased, whereas pulses of progesterone decreased, pulsatile hCG secretion.

The effect of dynorphin on placental pulsatile human chorionic gonadotropin secretion in vitro.

Using in vitro methods we have studied the effect of dynorphin (DYN) a natural k opioid receptor ligand upon hCG secretion in the first trimester placenta. In superfusion, where we have recently reported that hCG secretion is episodic, we found that the addition of 1-min pulses of DYN had a significant stimulatory effect upon pulsatile hCG secretion. This effect was seen at concentrations of 10(-8) mol/L-10(-11) mol/L. Higher doses (10(-6) mol/L) and lower doses (10(-12) mol/L) were ineffective. A 10-min administration was more effective than the 1-min pulses. Prolonged administration (90 min) caused an initial increase in pulsatile hCG secretion which was followed by a decrease to control values. However, upon stopping the prolonged opiate administration there was a substantial increase in hCG secretion. The involvement of opioid receptors in mediating the effect of DYN on hCG release was demonstrated by using naloxone, an opioid receptor antagonist. Coadministration of DYN, 10(-11) mol/L, and naloxone, 10(-10) mol/L, reduced markedly the effect of DYN. This was followed by a delayed increase in hCG secretion. Furthermore, des-tyrosine-DYN, the nonopioid derivative of DYN was 1000 times less potent in stimulating hCG release than DYN. The involvement of DYN in physiological control of placental hCG secretion is suggested.

The dual effect of epidermal growth factor upon human chorionic gonadotropin secretion by the first trimester placenta in vitro.

Epidermal growth factor (EGF) is believed to play an important role in the regulation of placental function. We have examined the effect of EGF upon first trimester (7-10 gestational weeks) placental hCG secretion and cellular differentiation using both static (explants and isolated cells) and kinetic (superfusion of explants) culture methods. In superfused explants, short (1-4 min) pulses of EGF increased both the rate and amplitude of spontaneous pulsatility of hCG. The frequency increased from 3/h to 5/h, and the amplitude increased compared to the control channels as calculated by the area under the curve. This effect was dose dependent and the concentration of 50 ng/ml, which was the lowest dose tested, was the most effective. In explants cultured for 24 h, EGF caused a 2-fold increase in hCG secretion, compared to control, P less than 0.05. In two different dispersed trophoblastic cell cultures, EGF added daily for the first week caused a 180% increase in hCG secretion, P less than 0.05. However, according to morphological criteria, i.e. light microscopy and vital staining, no significant effect upon the rate of differentiation to syncytiotrophoblast was observed in long-term cultures of one of these preparations. In conclusion, EGF plays a dual trophic role in stimulating hCG secretion in the first trimester. However, this effect is not dependent on cellular differentiation.

Progesterone, estradiol, and alpha-human chorionic gonadotropin secretion in patients with ectopic pregnancy.

Plasma free alpha hCG, estradiol (E2), and progesterone (P4) concentrations were measured in 38 patients with histologically confirmed ectopic pregnancy (EP). The menstrual gestational ages ranged from 6-10 weeks. Free alpha hCG levels, although significantly lower than those in women with a normal intrauterine pregnancy, increased markedly during this time period, from 1.5 to 11 ng/ml, a 7-fold increase. In women with an intrauterine pregnancy, only 0.6-fold increase occurred during the same time period. Plasma P4 and E2 concentrations in patients with EP were significantly lower, except at 6 weeks for E2 and in the sixth and seventh weeks for P4. The ectopically implanted trophoblast undergoes impairment of its ability to synthesize beta hCG, but not alpha hCG. The lack of utilization of alpha hCG in EP causes it to increase, while the level of intact hCG is low. These observations suggest that the levels of alpha hCG are a sensitive marker for placental well-being, and that it could serve as an additional diagnostic tool for the early diagnosis of EP. The placenta is only partially able to compensate for the reduced ovarian production of E2 and P4.

Are catechol oestrogens obligatory mediators of oestrogen action in the central nervous system? I. Characterization of pharmacological probes with different receptor binding affinities and catechol oestrogen formation rates.

In an attempt to define pharmacological probes with which to test the role of catechol oestrogen formation in the central nervous system, five oestrogens (oestradiol-17 beta, oestradiol-17 alpha, 4-fluoro-oestradiol, 2-fluoro-oestradiol and moxestrol (11 beta-methoxy-17 alpha-ethynyloestradiol) were studied for binding to oestrogen receptors and conversion to catechol metabolites. Binding to cytosol oestrogen receptors was measured in the hypothalamus-preoptic area-amygdala (HPA), pituitary gland and uterus of ovariectomized rats. Conversion to catechol oestrogens was tested in microsomes from the HPA, pituitary gland and liver, using a catechol-O-methyltransferase-coupled radioenzymatic assay. Oestradiol-17 alpha was the only weak oestrogen receptor ligand. Binding affinities of the other compounds tested were much higher and comparable to those of oestradiol-17 beta. In contrast, oestradiol-17 alpha was rapidly converted to catechol metabolites, while moxestrol was a relatively poor substrate for catechol oestrogen formation. 4-Fluoro-oestradiol could be 2-hydroxylated but not 4-hydroxylated. 2-Fluoro-oestradiol exhibited impaired 2-hydroxylation but normal 4-hydroxylation.

Increase in insulin binding and inhibition of the decrease in the phospholipid content of human term placental homogenates in culture by the sulfonylurea glipizide.

Term placental explants were cultivated for 48 hr without (control) and with various concentrations of glipizide. Maximum binding of [125I]-insulin in the control samples was decreased after 12 and 24 hr returning to initial values after 48 hr. In the presence of glipizide the binding was generally higher, reaching 180% (557 and 1000 nmol/L) of the corresponding control value (P < 0.01) after 48 hr owing to the presence of nearly 3-fold more (P < 0.05) receptors than in the untreated controls. Tissue cholesterol content was almost unaffected whereas both the phospholipid content and the corresponding phospholipid-to-cholesterol ratios were markedly, and in a time-dependent manner, increased by glipizide as compared to the controls. This was due to decreasing cholesterol and phospholipid concentrations in the controls during the time of culture as compared to initial values, and also to unchanged levels in glipizide-treated cultures. We conclude that glipizide affects placental insulin receptors and the phospholipid content of the tissue.

The effect of insulin on oestradiol and progesterone release by normal and diabetic placentae in vitro.

In an attempt to define better the metabolic differences between normal, insulin-dependent and non-insulin-dependent diabetes, we have compared the effect of insulin on the secretion of oestradiol and progesterone in term placental explant culture. Placentae from non-diabetic and from diabetic, non-insulin-dependent diabetic patients demonstrated a similar response to incubation with insulin. This response consisted of a dose-dependent increase in both oestradiol and progesterone in the incubation media after 24 h. In contrast, the placentae of insulin-dependent diabetics showed a decrease in oestradiol and no change in progesterone secretion following exposure to insulin. These differences in response to insulin may underlie other metabolic differences between the placentae in the different groups.

Stimulatory effect of prolactin on human placental progesterone secretion at term in vitro: possible inhibitory effect on oestradiol secretion.

Maternal and fetal circulating prolactin (PRL) increases 10-fold compared with the non-pregnant state. We examined the effect of PRL upon placental steroidogenesis. It had a significant (P less than 0.05) time-dependent stimulatory effect upon placental explants/P4 accumulation and secretion into the medium. The maximal stimulatory effect (two-fold) in dose-dependent experiments was found to be 200 ng/ml. The effect of PRL upon oestradiol secretion was mainly inhibitory. This inhibition was most pronounced at 200 ng/ml. In conclusion, placental steroid secretion is modulated by PRL. This effect occurs mainly at concentrations seen in the placenta at term, suggestive of its physiologic role.

Human embryonal extracts modulate placental function in the first trimester: effects of visceral tissues upon chorionic gonadotropin and progesterone secretion.

We investigated the effect of human first trimester fetal visceral organ extracts upon placental function, as evidenced by secretion of human chorionic gonadotropin and progesterone in explant cultures of 7-10 weeks gestational age trophoblast. Certain alcohol/water or water extracted embryonal tissues, in highly diluted solutions (1:100-1:2,000 final) had significant effects upon secretion of both hormones. The alcohol/water extract produced an opposite effect. This inhibitory effect was also seen when pulses of the water extract were added to the superfused trophoblast. Both heat inactivation at 57 degrees C and treatment with 10 microM p-chloromercurobenzoate eliminated the inhibitory effect, which suggests that the compounds in question are proteinaceous. Also dialysis with exclusion of less than 8,000 daltons abolished the inhibitory effect seen with the untreated water extract. The alcohol/water lung extract at 9 weeks inhibited, while at 10 weeks it stimulated P4 secretion. The water extracted lung had no effect upon P4 secretion. The alcohol/water extract of kidney had no consistent effect upon hCG secretion. The water extract effect was inhibitory. The effect of alcohol/water extract at 9 weeks upon P4 secretion was inhibitory while at 11 weeks it was stimulatory. The water extract had no effect upon P4 secretion. Both alcohol/water and water extracted adrenal inhibited hCG secretion. The alcohol/water extract also increased P4 secretion, while the water extract had no effect. The alcohol/water and water extract liver had no effect upon hCG secretion. The effect of alcohol/water upon P4 secretion was markedly stimulatory, while the water extract had no effect. In conclusion, fetal visceral organs in very dilute concentrations have a significant effect upon placental hormonal secretion in vitro. In case of the lung, the active compound(s) appears to be a protein with a molecular weight of less than 8,000 daltons. The role of the human embryo in modulating early trophoblastic function is suggested.