Gonadotropin-releasing hormone-associated peptide exerts a prolactin-inhibiting and weak gonadotropin-releasing activity in vivo

The in vivo effects of GnRH-associated peptide (GAP) on PRL, LH, and FSH release have been examined by injecting this peptide iv into the following types of conscious rats: 1) ovariectomized steroid-blocked females, 2) ether-stressed males, and 3) lactating females. GAP (2.4 X 10(-10) and 2.4 X 10(-9) mol) suppressed plasma PRL release but did not affect the levels of plasma LH and FSH in ovariectomized steroid-blocked rats. Furthermore, with 1-min etherization, GAP (1.6 X 10(-10) and 8.0 X 10(-10) mol) reduced the stress-induced rise of plasma PRL, but had no effect on the stress-induced decline of plasma gonadotropin levels in male rats. A single iv injection of GAP (8.0 X 10(-10) mol) into lactating rats before the onset of nursing did not block the elevation of plasma PRL induced by suckling. However, a second injection of GAP (1.6 X 10(-10) mol) at 30 min after the onset of suckling partially lowered plasma PRL levels 15 min later. By contrast, plasma FSH levels were significantly elevated by the second injection of GAP, and plasma LH also rose after iv administration of GAP in the nursing rats. These results indicate that the activity of GAP to stimulate FSH and LH release is limited, since GAP stimulated the release of FSH and LH only when plasma gonadotropin levels were extremely low. However, the in vivo evidence that GAP inhibited PRL release in a variety of conditions reinforces the possibility that GAP could be the peptidic PRL-inhibiting factor.     

Nitric oxide inhibits the release of norepinephrine and dopamine from the medial basal hypothalamus of the rat.

Previous research indicates that norepinephrine and dopamine stimulate release of luteinizing hormone (LH)-releasing hormone (LHRH), which then reaches the adenohypophysis via the hypophyseal portal vessels to release LH. Norepinephrine exerts its effect via alpha 1-adrenergic receptors, which stimulate the release of nitric oxide (NO) from nitricoxidergic (NOergic) neurons in the medial basal hypothalamus (MBH). The NO activates guanylate cyclase and cyclooxygenase, thereby inducing release of LHRH into the hypophyseal portal vessels. We tested the hypothesis that these two catecholamines modulate NO release by local feedback. MBH explants were incubated in the presence of sodium nitroprusside (NP), a releaser of NO, and the effect on release of catecholamines was determined. NP inhibited release of norepinephrine. Basal release was increased by incubation of the tissue with the NO scavenger hemoglobin (20 micrograms/ml). Hemoglobin also blocked the inhibitory effect of NP. In the presence of high-potassium (40 mM) medium to depolarize cell membranes, norepinephrine release was increased by a factor of 3, and this was significantly inhibited by NP. Hemoglobin again produced a further increase in norepinephrine release and also blocked the action of NP. When constitutive NO synthase was inhibited by the competitive inhibitor NG-monomethyl-L-arginine (NMMA) at 300 microM, basal release of norepinephrine was increased, as was potassium-evoked release, and this was associated in the latter instance with a decrease in tissue concentration, presumably because synthesis did not keep up with the increased release in the presence of NMMA. The results were very similar with dopamine, except that reduction of potassium-evoked dopamine release by NP was not significant. However, the increase following incubation with hemoglobin was significant, and hemoglobin, when incubated with NP, caused a significant elevation in dopamine release above that with NP alone. In this case, NP increased tissue concentration of dopamine along with inhibiting release, suggesting that synthesis continued, thereby raising the tissue concentration in the face of diminished release. When the tissue was incubated with NP plus hemoglobin, which caused an increase in release above that obtained with NP alone, the tissue concentration decreased significantly compared with that in the absence of hemoglobin, indicating that, with increased release, release exceeded synthesis, causing a fall in tissue concentration. When NO synthase was blocked by NMMA, the release of dopamine, under either basal or potassium-evoked conditions, was increased. Again, in the latter instance the tissue concentration declined significantly, presumably because synthesis did not match release. Therefore, the results were very similar with both catecholamines and indicate that NO acts to suppress release of both amines. Since both catecholamines activate the release of LHRH, the inhibition of their release by NO serves as an ultra-short-loop negative feedback by which NO inhibits the release of the catecholamines, thereby reducing the activation of the NOergic neurons and decreasing the release of LHRH. This may be an important means for terminating the pulses of release of LHRH, which generate the pulsatile release of LH that stimulates gonadal function in both male and female mammals.     

Congruence Between Latent Class and K-Modes Analyses in the Identification of Oncology Patients With Distinct Symptom Experiences

Context

Risk profiling of oncology patients based on their symptom experience assists clinicians to provide more personalized symptom management interventions. Recent findings suggest that oncology patients with distinct symptom profiles can be identified using a variety of analytic methods.

Primary-gaze diplopia in patients with thyroid-related orbitopathy undergoing deep lateral orbital decompression with intraconal fat debulking: a retrospective analysis of treatment outcome.

Our goal was to investigate the incidence of postoperative primary gaze diplopia in patients with thyroid-related orbitopathy (TRO) undergoing deep lateral wall orbital decompression surgery with intraconal fat debulking in the Jules Stein Eye Institute over a period of 4(1/4) years. Overall 201 orbital decompression surgeries were performed in 116 patients (23 males, 93 females). All surgeries were performed by two of the authors (R.A.G. and J.D.M.) and in the noninflammatory phase of the disease. Exophthalmos decreased by an average of 3.4 +/- 2.7 mm from 23.8 +/- 3.2 mm (17-31) to 20.4 +/- 2.5 mm (14-29), p < 0.001, 95% confidence interval (CI) (3.0:3.8). 31% of patients had preoperative primary gaze diplopia and 28.4% had postoperative primary gaze diplopia. Thirty (83%) of the 36 patients with preoperative diplopia had also postoperative diplopia; 6 (16.7%) of the 36 patients had improvement in diplopia following deep lateral wall decompression. Of the 80 (69%) of patients without preoperative double vision 3 developed postoperative double vision in primary gaze (2.6% of all patients). These 3 patients were older (56 versus 46 years, p = 0.047), had more limitation in ocular movements (p = 0.017) and achieved more decrease in proptosis with surgery (6 versus 3.1 mm, p = 0.024). No complications were associated with orbital decompression. In conclusion deep lateral wall orbital decompression surgery with intraconal fat debulking is associated with a low rate (2.6%) of new-onset primary gaze diplopia. Some patients (5.2%) with preoperative diplopia actually had improvement in diplopia postoperatively. This surgery is effective in reduction of congestion and exophthalmos, and is not associated with detrimental effects on visual acuity.