Objective: VEGF is produced and released by granulosa-theca and endotelial cells. This factor is related to increase the vascular permeability and has also been related to ovarian response to ovarian stimulation(COH). The purpose of the present study was to compare the concentration of VEGF in the serum and follicular fluid from women undergoing controlled ovarian hyperstimulation treated with GnRH antagonist or agonist. Design: Prospective study. Materials/Methods: Twenty women with primary infertility undergoing IVF were included. Patients were randomized to two different COH protocols: (1): long mid luteal suppression with GnRH agonist, Triptorelin (Decapeptyl®0.1, Ipsen-Pharma) or (2) multiple doses of GnRH antagonist (Cetrotide® 0.25; Serono) with recombinant FSH (Gonal F®, Serono). In both groups ovarian stimulation was started on day 3 with 225 UI for 4 days, then individual dosage was adjusted according the follicular growth. Antagonist was started on day 6 until the day HCG administration. Blood samples were obtained in the first day of ovarian stimulation and daily after day 5 up to HCG administration. The day of ovum pick up, follicular fluid (FF) of 5 mature follicles (>16 mm diameter) was polled and also blood was withdrawn for analysis. VEGF was determined in serum and FF by ELISA (Quantikine®R&DSystens). Results: No significant differences were found between both groups in age (25.5 ± 6.1 vs 27.0 ± 4.0), length of stimulation days (7.8 ± 1.4 vs 9.1 ± 1.7), total FSH dose (1339 ± 226 vs 1596 ± 279), number of oocytes obtained (12 ± 6.7 vs 17.2 ± 5.7), number of metaphase II oocytes (10.2 ± 5.7 vs 15.4 ± 4.8) and fertilization rate (78.3% vs 81.4%). Conclusions: VEGF serum levels are stimulated by gonadotropins and down-regulated by both, agonists and antagonists of GnRH. However, FF VEGF levels are higher in antagonist cycles, suggesting that the process of angiogenesis may be less affected under this regimen of ovarian stimulation. Table TableVEGF serum and follicular fluid levels (pg/ml)Day 2–3Day 5Day 6Day 7Day HCGVEGF Follicular Fluid (pg/ml)Antagonist0,36 ± 0,20,57 ± 0,1†p < 0,050,51 ± 0,2†p < 0,050,37 ± 0,010,40 ± 0,190,46 ± 0,25Agonist0,28 ± 0,10,33 ± 0,1†p < 0,050,25 ± 0,1†p < 0,050,23 ± 0,060,30 ± 0,070,37 ± 0,17† p < 0,05 Open table in a new tab

BACKGROUND:Impaired antioxidant defense and increased lipid peroxidation has been reported in chronic schizophrenic patients. Recently, we have reported an impaired antioxidant defense in never medicated first-episode schizophrenic and schizophreniform patients. We report now a concomitant increase in plasma lipid peroxides.METHODS:The plasma lipid peroxides [thiobarbituric acid reactive substances (TBARS)] were analyzed by chemical and high performance liquid chromatography procedures in 26 patients admitted for a first episode of schizophrenic (N = 17) or schizophreniform psychosis (N = 9) and 16 normal control subjects. The patients had a duration of 4.5 days (SD 2.8) of psychosis at the time of the study.RESULTS:Plasma TBARS levels were significantly higher in the patients than in normal controls (P < .002). TBARS levels were above the normal range in 16 of the 26 patients. Higher TBARS levels were associated with a greater severity of negative symptoms and lower red blood cell activity of the glutathione peroxidase.CONCLUSIONS:The findings indicate ongoing oxidative injury at the very onset of psychosis. If valid, this would indicate the need for adjunctive antioxidant treatment from the beginning of the course of nonaffective psychoses. This might prevent a deteriorating course and development of the deficit syndrome.

Previous studies found peripheral activities of antioxidant enzymes to be abnormal in schizophrenic patients. It is not understood whether this is integral to the disease process or a result of long-term treatment with neuroleptics. Red blood cell activities of three antioxidant enzymes — superoxide dismutase, glutathione peroxidase, and catalase — were therefore examined in 14 drug-naive, first episode patients with a diagnosis of schizophrenia or schizophreniform disorder and 10 normal subjects. The patients had an average duration of psychosis of 4.46 days (SD 2.5). Superoxide dismutase activity was significantly lower in patients than in normal controls, with no difference between the groups in activities of the other two enzymes. Lower superoxide dismutase activity was associated with deterioration of school functioning from childhood to early adolescence and a history of poorer school functioning during early adolescence. These findings indicate a compromised antioxidant defense at the onset of psychosis, and suggest that oxidative injury might contribute to adverse developmental events in the pathogenic cascade of schizophrenia.

We have previously measured the individual content of immunoreactive vasopressin (AVP), oxytocin (OT) and vasotocin (AVT) in 155 human pineal glands, and report here identification and measurement of the neurophysin (Np) content of the same glands, using specific homologous human neurophysin I (HNp I) and neurophysin II (HNp II) radioimmunoassays. Median values for HNp I were for men 47 ng/gland (range, 5 to 1360) and for women 24 ng/gland (range, 5 to 1000); median values for HNp II were respectively 7 ng/gland (range, 2 to 191) and 15 ng/gland (range, 2 to 356) with no significant difference between men and women for HNp I and HNp II but a significant difference (p<0.001) between HNp I and HNp II for both sexes. Gel filtration showed that pineal neurophysins were eluted at the same volume as both standard Np and Np from human posthypophyses used as controls. HNp I correlated both with AVP (rs=0.54 for men and 0.55 for women) and OT (rs=0.86 for men and 0.57 for women) but not with AVT, while HNp II correlated with AVP (rs=0.52 for men and 0.53 for women) and OT (rs=0.92 for men and 0.50 for women) but not with AVT. This study thus confirms the presence of two neurophysins in the human pineal gland and further indicates that they are related to AVP and OT concentrations in the same gland. The results also imply, however, that the presence of immunoreactive AVT (more probably a closely related peptide) is independent of the neurophysins.

Hamsters are highly-dependent upon the central actions of progesterone (P) to facilitate sexual behavior. P has membrane mechanisms of action in the ventral tegmental area (VTA) to facilitate sexual receptivity of rodents. The present experiments examined whether P's membrane actions in the VTA include dopamine (DA) type 1 (D1) or dopamine type 2 (D2) receptors. Ovariectomized (ovx), estradiol (E2)- and P-primed hamsters were infused with D1 (Experiment 1) or D2 (Experiment 2) antagonists or agonists (0 or 100 ng) to the VTA and tested 30 min later. The D1 agonist, SKF38393, enhanced P-facilitated lordosis. The D1 antagonist, SCH23390, attenuated P-facilitated lordosis. The D2 agonist, quinpirole and the D2 antagonist, sulpiride, had no significant effects on P-facilitated lordosis. These data suggest that, in hamsters, P's actions for lordosis may involve D1 receptors in the VTA.

1. The cells in this study responded with a hyperpolarization to the following agents in this order of potency; dopamine > noradrenaline phenylephrine = octopamine.2. 6,7 ADTN had a relative potency of 0.1 compared to dopamine. 5,6 ADTN did not inhibit the cells in this study.3. The D1 receptor agonists SKF38393 and dihydroxynomifensine mimicked the effect of dopamine on these cells but were over 100 times less active, whereas the D2 selective agonists quinpirole and RU24213 were without effect.4. Both the D1 antagonist SCH23390 and the D2 antagonist sulpiride antagonised the dopamine response with pA2 values of 6.1 and 6.7, respectively.5. Five cells that responded to dopamine with a hyperpolarization were depolarized by noradrenaline. The order of potency of compounds at eliciting this depolarization, noradrenaline > phenylephrine > octopamine indicated that this response may be mediated by a noradrenaline-preferring receptor.

To compare the relative strength of incorporation and adhesion formation for mesh hernia repairs performed with Sepramesh (Genzyme Corp., Cambridge, Massachusetts) and Dualmesh (WL Gore and Assoc., Flagstaff, Arizona).A prospective randomized study was conducted using 30 New Zealand white rabbits, with 15 animals randomized to each limb. A standardized abdominal defect was created in each animal. The defect was then repaired using either Sepramesh or Dualmesh. Animals were sacrificed at 4 weeks. The area of adhesions was determined using digital analysis of inked specimens. Strength of incorporation was determined using an Instron Tensiometer. (Department of Clinical Research, D. D. Eisenhower Army Medical Center, Fort Gordon, GA 30905.)Sepramesh had a 30.6% stronger strength of incorporation compared with Dualmesh. (p = 0.011) The difference in area of adhesions was not statistically significant between the 2 products.The use of Sepramesh for abdominal hernia repairs provides a significantly stronger strength of incorporation without increasing the amount of adhesions as compared with Dualmesh.

hormone (TSH) levels (p = 0.02). Depressed hypothyroid patients had higher TSH levels (p < 0.001) and lower cortisol responses relative to matched controls (p = 0.03) than their nondepressed counterparts. These findings support animal work suggesting that hypothyroidism reduces central 5-HT activity. They also suggest a threshold effect in that those with the highest TSH levels had the lowest 5-HT-mediated endocrine responses and were most likely to be diagnoses as depressed.

Findings from in vivo NMR spectroscopic studies and studies of peripheral tissues from schizophrenic patients implicate altered cell membrane lipid metabolism. Aside from structural functions, cell membrane fatty acids are integrally involved in second messenger systems and prostaglandin synthesis. We examined the fatty acid composition of cell membranes of cultured skin fibroblasts from 12 schizophrenic patients (8 were drug-naive), 8 normal controls, and 6 chug-free bipolar patients. The most salient findings ,sere a significantly lower content of 22 carbon fatty acids, especially 22:6n-3 (docosahexanoic acid, DHA) and a higher ¢06:¢o-3 fatty acid ratio in fibroblasts from schizophrenic patients, but not in those from bipolar patients. Given that DHA precursor levels were not low, this suggests that schizophrenia may be associated with impaired activity of **4-desaturase, which converts 22:5n-3 to 22:6n-3 (DHA) and 22:4n-6 to 22:5n-6. DHA is highly concentrated in the brain, especially in synaptic membranes, and DHA deficiency results in impaired learning in animal models. Two studies found RBC DHA levels to be lower in schizophrenic patients with prominent negative symptoms and, in the steady state, RBC DHA reliably reflects brain DHA levels. The hypothesis will be presented that deficiency of omega-3 fatty acids, especially DHA, contributes to the deficit syndrome of schizophrenia, and may explain crossnational differences in outcome observed in the WHO studies and the effects of in utero exposure to influenza vires or severe famine on its incidence.

Contents of plasma membrane major phospholipids, cholesterol, and cholesteryl esters of fibroblasts from drug-naive psychotic patients were compared with those from normal controls. Total membrane lipids were extracted and individual lipids were separated on high-performance thin-layer chromatography. The contents of lipid bands were quantitated by densitometric scanning and comparing with standards. Contents of total phospholipids as well as phosphatidylserine, phosphatidylinositol and phosphatidylethanolamine were significantly lower in fibroblasts from patients than in those from normal controls (P<0.001, <0.005, <0.05, <0.05 respectively). Total cholesterol fraction and cholesteryl esters were also significantly lower in fibroblasts from patient (P <0.005, <0.001 respectively). These changes were not related to differences in age or sex. These data support the hypothesis that schizophrenia is associated with disordered membrane lipid metabolism, and that this predates the onset of psychosis.