The kallikrein-kinin system, but not vascular endothelial growth factor, plays a role in the increased vascular permeability associated with ovarian hyperstimulation syndrome

The association between retrospectively reported childhood conduct disorder (CD) and a history of alcohol dependence (AD) was examined in a sample of 2,682 male, female, and unlike-sex adult twin pairs. There was a strong association between CD and AD in both men (tetrachoric r = .34, odds ratio = 2.8) and women (tetrachoric r = .53, odds ratio = 9.9). Genetic factors accounted for most of the association between CD and AD liability in men and women, with the remainder of the association being due to nonshared individual-specific environmental factors. Genetic influences common to CD and AD accounted for 17% and 35% of the genetic variation in AD liability in men and women, respectively, and accounted for 11% and 23% of the total variation in AD liability in men and women, respectively. The results suggest that there are common genetic risk factors for CD and AD or that CD itself is an important genetically influenced risk factor for AD.     

Plasma immunoglobulins in patients with severe ovarian hyperstimulation syndrome

By histochemical and immunohistochemical methods, the presence of cholinergic-like molecules has previously been demonstrated in Paramecium primaurelia, and their functional role in mating-cell pairing was suggested. In this work, both true acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities were electrophoretically investigated, and the presence of molecules immunologically related to BuChE was checked by immunoblotting. The AChE activity, shown in the membrane protein fraction of mating-competent cells and in the cytoplasmic fraction of immature cells, is due to a 260-kDa molecular form, similar to the membrane-bound tetrameric form present in human erythrocytes. This AChE activity does not appear in either the cytoplasmic fraction of mating-competent cells or in the membrane protein fraction of immature cells. No evidence was found for the presence or the activity of BuChE-like molecules. The role of AChE in P. primaurelia developmental cycle is discussed.     

Acute cerebrovascular accidents with severe ovarian hyperstimulation syndrome

Cerebrovascular complications are by far the most serious side-effects of ovarian hyperstimulation syndrome. We report a case in which the patient developed cerebral infarction with right sided hemiplegia as a result of severe hyperstimulation syndrome after using a gonadotrophin-releasing hormone agonist for intracytoplasmic sperm injection.     

A potential role for angiotensin II-induced vascular endothelial growth factor expression in the pathogenesis of diabetic nephropathy?

The relationship between sensory quality of carrots and their contents and composition of essential oils and total sugars as influenced by nitrogen fertilization was investigated. Carrots (Daucus carota L.) of the variety 'Nanthya' F1 (S&G Sandoz Seeds) were grown in Weihenstephan 1996 with three levels of inorganic nitrogen fertilization (3 levels in 4 replications). Medium- and higher-boiling flavour-components were extracted as essential oils and separated gas-chromatographically (GC-FID). Lower-boiling flavour-components were taken from the headspace and analysed chemosensorially. The human sensory assessments were performed by an untrained panel of 300 people (students and employees of the TU München)--these results were compared with those of the chemical analyses. Carrots with lower nitrogen application were found to taste more intensive, more fruity, sweeter and better and at the same time less bitter and less earthy. They had higher contents of total sugar and a higher percentage of dry matter. Fertilization with nitrogen does not only affect the quantity but also the composition of the essential oils. The taste intensive was positively correlated with the quantity of essential oils, the taste sweet was positively correlated with the content of total sugars. It was possible to differentiate the carrots from each other by chemo-sensorial headspace analyses according to their N-fertilization levels.     

In controlled ovarian hyperstimulation, steroid production, oocyte retrieval, and pregnancy rate correlate with gene expression of vascular endothelial growth factor

PURPOSE: Whether the gene expression of vascular endothelial growth factor (VEGF) in human granulosa cells is a predictor of fertilization was evaluated in patients participating in an in vitro fertilization program. METHODS: Fifty patients with normal ovaries who were participating in an in vitro fertilization program at the University of Milan, San Raffaele Scientific Institute, were included in the study. We correlated E2 and P serum levels on the day of oocyte collection, the number of follicles, oocytes collected, and fertilized, and pregnancies with mRNA for VEGF of luteinizing granulosa cells obtained at the time of oocyte retrieval. RESULTS: Comparing E2 and P serum levels, the number of follicles, oocytes collected and fertilized, and pregnancies with gene expression for VEGF, we found a positive correlation. E2 and P serum levels were higher in patients with increased VEGF (P < 0.01). Furthermore, there were more follicles, oocytes collected and fertilized, and pregnancies in patients with maximum expression of VEGF, and the difference was statistically significant (P < 0.05). CONCLUSIONS: Our results suggest that VEGF may be important for vascular development during follicular growth and luteal differentiation, oocyte maturation, and fertilization.     

Vascular permeability/vascular endothelial growth factors: a potential role in the pathogenesis and treatment of vascular diseases

The objective was to investigate if the presence of the v-Ha-ras oncogene could induce immune changes different to the ones observed in normal mice. Therefore, we decided to use Oncomice, the transgenic mice with an activated v-Ha-ras oncogene under the control of the mouse mammary tumor virus-promoter, and their normal inbred counterparts, FVB mice. Both strains of mice were fed the Lieber-DeCarli liquid diet with ethanol or the isocaloric control diet and were injected daily with cocaine or saline. The percentage and absolute number of T and B lymphocytes in the spleen and thymus were determined. The in vitro production of TNF-alpha (tumor necrosis factor-alpha), IL-2 (interleukin-2) and IFN-gamma (interferon-gamma) by spleen cells, and the levels of serum sIL-2R (soluble IL-2 receptor) were also measured. Oncomice fed the Lieber-DeCarli ethanol diet or receiving either saline or cocaine injections presented a higher tumor incidence than Oncomice receiving the control diet. A reduced total number of thymocytes as well as absolute number of cells in all the subsets was found in Oncomice. Moreover, a decreased percentage of CD8+ cells was also observed in Oncomouse spleens. These features were even more marked in ethanol-treated Oncomice. Higher serum sIL-2R levels were observed in Oncomice, especially in mice treated with ethanol or cocaine. The results suggest that the oncogene product, P21ras, plays an important role in dysregulating the immune system and hence in favoring tumorigenesis.     

Transcriptional regulation of vascular endothelial growth factor gene expression in ovarian bovine granulosa cells

From rape (Brassica napus) seedlings proteins able to bind fatty acids and their CoA-esters were purified by gel filtration and cation-exchange chromatography. Among the four proteins detected, one of them (peak IV) appeared purified to homogeneity. This protein is a monomer with a molecular mass of about 9 kDa, as estimated by gel filtration and by polyacrylamide gel electrophoresis. The isoelectric point of the rape protein was higher than 10.5 as determined by chromatofocusing. The pure rape protein appeared furthermore to be able to transfer several phospholipids (phosphatidylcholine, phosphatidylinositol and phosphatidylethanolamine) between membranes. The rape protein, having a multifunctional property, was thus called acyl-binding/lipid-transfer protein (AB-LTP). In order to compare this protein to plant lipid-transfer proteins (LTPs), its structure was determined. The amino acid analysis of the rape AB-LTP revealed a high amount of alanine, an absence of histidine and tryptophan and the presence of eight cysteine residues. The N-terminal amino acid sequence of the rape protein revealed a high homology to plant LTPs. These observations led us to propose that the rape AB-LTPs belong to a category of plant proteins interacting with lipids and playing a role in the fatty acid dynamics.     

Febrile morbidity in severe and critical ovarian hyperstimulation syndrome: a multicentre study

The objective of this study was to define the incidence of febrile morbidity and its causes in severe and critical ovarian hyperstimulation syndrome (OHSS). For this purpose, we reviewed the medical records of all OHSS patients hospitalized in 16 out of 19 tertiary medical centres in Israel between January 1987 and December 1996. Febrile morbidity was defined as at least one episode of temperature rise above 38 degrees C lasting > or =24 h. A total of 2902 patients (3305 hospitalizations) with OHSS was identified, of whom 196 had severe, and 13 critical, OHSS. Among the 209 patients investigated the incidence of febrile morbidity was 82.3%, of which 20.5% was attributed to urinary tract infection, 3.8% to pneumonia, 3.3% to upper respiratory tract infection, 2.0% to intravenous line phlebitis, 1.0% to cellulitis at an abdominal puncture site, 1.0% to postoperative wound infections and 0.5 % to gluteal abscess at the site of progesterone injection. Non-typical organisms were frequently isolated, such as Pseudomonas, Proteus, Klebsiella and Enterobacter species. No infectious aetiology was found in 105 patients (50.2%). Hypoglobulinaemia was recorded in most patients, while ascitic and pleural fluids aspirated from these patients contained high globulin concentrations. We conclude that infection-related febrile morbidity in severe and critical OHSS is high, and may be attributed to some degree of immunodeficiency associated with loss of plasma globulins to the third space. However, non-infection-related febrile morbidity is even higher and may be attributed to endogenous pyrogenic mechanisms.     

Overproduction of vascular endothelial growth factor/vascular permeability factor is causative in Crow-Fukase (POEMS) syndrome

Crow-Fukase or POEMS syndrome of polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes is a rare multisystem disorder of obscure pathogenesis that is associated with microangiopathy, neovascularization, and accelerated vasopermeability. We examined the levels of the vascular endothelial growth factor/vascular permeability factor (VEGF) in the serum and cerebrospinal fluid (CSF) from 10 patients with this syndrome. Serum VEGF levels were about 15-30 times those in control subjects or patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and other neurological disorders. The CSF VEGF levels, however, were similar to those found in GBS and CIDP. Elevated VEGF levels in the serum decreased in 7 patients with Crow-Fukase syndrome after conventional therapy. The principal isoform of VEGF in Crow-Fukase syndrome was VEGF165. Elevated VEGF was independent of M-protein. Our results suggest that the overproduction of VEGF is important in the pathogenesis of this disorder.     

青蒿琥酯对急性单核细胞白血病SHI-1细胞株血管内皮生长因子及其受体表达的影响

目的 研究青蒿琥酯对急性单核细胞白血病SHI-1细胞株血管内皮生长因子(VEGF)及其受体( VEGFR)的影响。方法酶联免疫吸附法检测非细胞毒性浓度(5、10、20 ng/ml)青蒿琥酯作用SHI-1细胞后培养上清液VEGF浓度,流式细胞术检测有或无青蒿琥酯作用时,SHI-1细胞表面VEGFR-1及VEGFR-2阳性表达率。结果培养24、48 h后,无青蒿琥酯作用的SHI-1细胞培养上清液VEGF质量浓度分别为( 980.3±2.2)、(982.4±2.3) pg/ml,VEGFR-1表达率分别为(5.40±3.11)％和(4.45±2.85)％,VEGFR-2表达率分别为(13.90.± 2.26)％和（13.95±1.96）％。5、10、20 ng/ml青蒿琥酯作用24h后,SHI-1细胞培养上清液VEGF质量浓度分别为(234.6±1.8)、(114.9±1.6)、(108.8±1.5) pg/ml,作用48 h后分别为(62.3±1.7)、(60.9±1.6)、(32.7±1.7) pg/ml,与培养相同时间无青蒿琥酯组相比,VEGF浓度明显下降（均P＜ 0.05）,且相同浓度青蒿琥酯作用24 h与48 h间差异亦有统计学意义(均P＜ 0.05)。5、10、20 ng/ml青蒿琥酯作用24 h,VEGFR-1阳性率分别为(4.30±2.21)％、(4.20±1.37)％和(3.90±1.86)％,作用48 h后分别为(3.80±2.87)％、(3.60±1.73)％和(3.00±1.82)％,相同作用时间不同浓度青蒿琥酯组间及相同浓度作用不同时间组间VEGFR-1阳性率差异均无统计学意义(均P＞ 0.05);作用24h后,SHI-1细胞VEGFR-2阳性率分别为(4.40±1.15)％、(3.10±0.68)％和(1.10±0.72)％,作用48 h后分别为(3.00±1.68)％、(2.20±0.93)％和(0.60±0.92)％,3个不同浓度青蒿琥酯作用相同时间后VEGFR-2表达率降低（均P＜ 0.05）,相同浓度作用24与48 h间差异均无统计学意义（均P＞ 0.05）。结论SHI-1细胞株高分泌VEGF,青蒿琥酯可下调VEGF分泌及VEGFR-2的表达,而对VEGFR-1表达的调节作用不显著。     

does intravenous administration of human albumin prevent severe ovarian hyperstimulation syndrome?

OBJECTIVE: To report our experience with i.v. albumin as a means to prevent ovarian hyperstimulation syndrome (OHSS) in high-risk patients. DESIGN: Retrospective case-series. SETTING: University hospital-based IVF program. PATIENTS: Five women undergoing controlled ovarian stimulation for IVF-Based on previous history and/or E2 measurements and number of ovarian follicles, these patients were considered to be at high risk for developing OHSS. INTERVENTIONS: Intravenous albumin was given at the time of oocyte retrieval. Additional doses were given 12 and 24 hours later. MAIN OUTCOME MEASURE: Development of OHSS. RESULTS: Four patients developed OHSS; two of them had the severe form of the syndrome. CONCLUSIONS: Severe OHSS may develop in high-risk patients despite the prophylactic administration of i.v. albumin.     

Expression of vascular endothelial growth factor and placenta growth factor in human placenta

Normal development and function of the placenta requires invasion of the maternal decidua by trophoblasts, followed by abundant and organized vascular growth. Little is known of the significance and function of the vascular endothelial growth factor (VEGF) family, which includes VEGF, VEGF-B, and VEGF-C, and of placenta growth factor (PIGF) in these processes. In this study we have analyzed the expression of VEGF and PIGF mRNAs and their protein products in placental tissue obtained from noncomplicated pregnancies. Expression of VEGF and PIGF mRNA was observed by in situ hybridization in the chorionic mesenchyme and villous trophoblasts, respectively. Immunostaining localized the VEGF and PIGF proteins in the vascular endothelium, which was defined by staining for von Willebrand factor and for the Tie receptor tyrosine kinase, an early endothelial cell marker. VEGF-B and VEGF-C mRNAs were strongly expressed in human placenta as evidenced by Northern blot analysis. These data imply that VEGF and PIGF are produced by different cells but that both target the endothelial cells of normal human term placenta.     

Role of vascular endothelial growth factor in ovarian cancer: inhibition of ascites formation by immunoneutralization

Ovarian cancer is characterized by the rapid growth of solid intraperitoneal tumors and large volumes of ascitic fluid. Vascular endothelial growth factor (VEGF) augments tumor growth by inducing neovascularization and may stimulate ascites formation by increasing vascular permeability. We examined the role of VEGF in ovarian carcinoma using in vivo models in which intraperitoneal or subcutaneous tumors were induced in immunodeficient mice using the human ovarian carcinoma cell line SKOV-3. After tumor engraftment (7 to 10 days), some mice were treated with a function-blocking VEGF antibody (A4.6.1) specific for human VEGF. A4.6.1 significantly (P < 0.05) inhibited subcutaneous SKOV-3 tumor growth compared with controls. However, tumor growth resumed when A4.6.1 treatment was discontinued. In mice bearing intraperitoneal tumors (IP mice), ascites production and intraperitoneal carcinomatosis were detected 3 to 7 weeks after SKOV-3 inoculation. Importantly, A4.6.1 completely inhibited ascites production in IP mice, although it only partially inhibited intraperitoneal tumor growth. Tumor burden was variable in A4.6.1-treated IP mice; some had minimal tumor, whereas in others tumor burden was similar to that of controls. When A4.6.1 treatment was stopped, IP mice rapidly (within 2 weeks) developed ascites and became cachectic. These data suggest that in ovarian cancer, tumor-derived VEGF is obligatory for ascites formation but not for intraperitoneal tumor growth. Neutralization of VEGF activity may have clinical application in inhibiting malignant ascites formation in ovarian cancer.     

Human neutrophils secrete vascular endothelial growth factor

Vascular endothelial growth factor (VEGF) is a multifunctional cytokine that plays a pivotal role in mediating neovascularization as well as other endothelial cell alterations during inflammation. In this study, we demonstrate that human neutrophils are a source of VEGF. We observed that isolated blood neutrophils released VEGF in response to different stimuli and we demonstrated by immunohistochemistry that neutrophils infiltrating inflamed tissues contain VEGF. These results indicate that neutrophil-derived VEGF may be instrumental in regulating vascular responses during acute and chronic inflammation.