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At least 397 records · Page 22Linked to original sources

PubMed2006

Clozapine bioactivation induces dose-dependent, drug-specific toxicity of human bone marrow stromal cells: a potential in vitro system for the study of agranulocytosis.

Clozapine, an atypical antipsychotic drug effective in treatment of refractory schizophrenia causes potentially life-threatening agranulocytosis. The drug undergoes bioactivation to a toxic, chemically reactive intermediate with capacity to target stromal cells, central components of the bone marrow microenvironment implicated in neutrophil development. To identify possible mechanisms underpinning disruption of stroma as a site of drug bioactivation, toxicity was induced in vitro. Therefore metabolite generation procedures utilizing HOCl or HRP-H(2)O(2) as primary components involved in clozapine metabolism were adapted for stromal culture and coupled with viability determinations. Drug oxidation by HOCl was less toxic to stromal cells than HRP-H(2)O(2) based methods. More specifically, clozapine bioactivation by HRP-H(2)O(2) caused dose-dependent inhibition of stromal viability at therapeutically relevant concentrations. Differences in susceptibility of HAS303 and LP101 cells to the clozapine nitrenium ion were also evident. Stromal cell death was attributed to clozapine in the presence of a complete metabolising system comprising HRP and H(2)O(2). In the absence of a complete metabolising system clozapine was not cytotoxic. For LP101 cells, drug plus HRP (minus H(2)O(2)) also induced toxicity. Importantly, other antipsychotic drugs including risperidone, olanzapine and haloperidol when bioactivated, were not cytotoxic, indicating system specificity for clozapine. Exogenous GSH, N-acetylcysteine, l-ascorbic acid, catalase, and sodium azide afforded protection to cells whereas S-methylGSH, GSSG, ketoprofen and proadifen did not. Thus functional data derived from the in vitro stromal system defined in these studies may enable further investigation of the mechanisms subserving stromal impairment in clozapine-induced agranulocytosis and direct attention to improved methods for its prevention.

Agranulocytosis↗

PubMed2004

Osteoblast response to bioactive glasses in vitro correlates with inorganic phosphate content.

Inorganic phosphate (Pi) is a physiological regulator of osteoblasts and chondrocytes, suggesting that phosphate may contribute to the biological response of these cells to bioactive glasses like Bioglass 45S5, which is composed of 45% SiO2, 24.5% CaO, 24.5% Na2O, and 6% P2O5. We investigated the effect of varying the Pi content of bioactive glass disks (0%, 3%, 6% and 12% P2O5) using human osteoblast-like MG63 cells as the model. Cell number on 6% Pi disks was comparable to cultures on tissue culture plastic, but was reduced at higher and lower Pi concentrations. Alkaline phosphatase specific activity of isolated cells and cell layer lysates, as well as PGE2, TGF-beta1 and NO levels in conditioned media, were elevated in cultures grown on bioactive glass and varied with the Pi content. The greatest effects were observed in cultures grown on disks with the lowest Pi concentrations. Thus, growth on the bioactive glasses enhances cell function in comparison with tissue culture plastic and lower Pi content favors osteoblast differentiation.

Biocompatible Materials↗

PubMed2005

The effect of bioactive glasses on bone marrow stromal cells differentiation.

Bone marrow is a mixture of hematopoietic, vascular, stromal and mesenchymal cells capable of skeletal repair/regeneration thanks to the ability of bone marrow cells to differentiate into osteoblasts and osteoclasts. This ability is important in tissue regeneration during fracture healing, or for successful osteointegration of implanted prostheses, and in bone remodelling. Therefore, bone marrow cell culture systems seem to be useful and relatively close to in vivo conditions models to study interactions occurring at the cell-material interface of implants directed to hard tissue engineering. The purpose of this study was to investigate the ability of three bioactive glasses (45S, 58S and 77S) to induce osteogenic differentiation and cell mineralisation. A significant effect of the 45S and 77S bioactive materials was seen on early differentiation of the marrow stromal cells into osteoblast-like cells. 45S bioglass evidenced also the highest effect on cell mineralisation at the same level as cells treated with dexametasone, used as positive control. 77S treated cells evidenced also a significant inhibition in the number of multinucleated TRAP-positive cells (ostoclast-like cells) in comparison with the control untreated cells and in marrow cells treated with 45S and 58S bioactive glasses. These findings have potential implications and applications for tissue engineering where three-dimensional bioactive glass substrates could be used as scaffolds for in vitro production of bioengineered bone.

Animals↗

PubMed2005

Mechanical properties and osteoconductivity of porous bioactive titanium.

Porous bioactive titanium implants (porosity of 40%) were produced by a plasma-spray method and subsequent chemical and thermal treatments of immersion in a 5M aqueous NaOH solution at 60 degrees C for 24 h, immersion in distilled water at 40 degrees C for 48 h, and heating to 600 degrees C for 1 h. Compression strength and bending strength were 280 MPa (0.2% offset yield strength 85.2 MPa) and 101 MPa, respectively. For in vivo analysis, bioactive and nontreated porous titanium cylinders were implanted into 6mm diameter holes in rabbit femoral condyles. The percentage of bone-implant contact (affinity index) of the bioactive implants (BGs) was significantly larger than for the nontreated implants (CGs) at all postimplantation times (13.5 versus 10.5, 16.7 versus 12.7, 17.7 versus 10.2, 19.1 versus 7.8 at 2, 4, 8 and 16 weeks, respectively). The percentage of bone area ingrowth showed a significant increase with the BGs, whereas with the CGs it appeared to decrease after 4 weeks (10.7 versus 9.9, 12.3 versus 13.1, 15.2 versus 9.8, 20.6 versus 8.7 at 2, 4, 8 and 16 weeks, respectively). These results suggest that porous bioactive titanium has sufficient mechanical properties and biocompatibility for clinical use under load-bearing conditions.

Animals↗

PubMed2005

Release characteristics and bioactivity of gelatin-tricalcium phosphate membranes covalently immobilized with nerve growth factors.

The gelatin-tricalcium phosphate membranes were cross-linking with low concentration glutaraldehyde solution (GTG). This material has good mechanical property, biocompatibility, and is feasible for surgical manipulation. For axonal regeneration, nerve growth factors (NGF) were immobilized onto the composite (GTG) with carbodiimide. The purpose of this study was to evaluate the release characteristics and bioactivity of NGF after covalent immobilization onto the GTG membranes (GEN). NGF immobilized onto and released from the composite was quantified using ELISA method. PC 12 cells were cultured on the GTG and GEN composites. Cell survival, cytotoxicity, and cellular activity were evaluated by total protein content, LDH activity, and MTT assay respectively. Neurite outgrowth assay was used to evaluate the biological activity of NGF released from GEN composite. From ELISA measurement, the releasing curve for NGF showing two distinctive parts with different slopes indicated that NGF were released from the composite in diffusion-controlled mechanism and degradation-controlled mechanism respectively. While culturing with PC 12 cells, LDH leakage results implied that whether GTG composite cross-linked with NGF or not showed little cytotoxicity. The total protein content and cellular activity of PC 12 cells were lower on GTG and GEN membranes than control group. However, 56%+/-3.98 of PC 12 cells showed significant neurite outgrowth on GEN membranes which was statistically higher than GTG without NGF immobilization. In addition, sustained release of bioactive NGF for two months had been demonstrated by neurite outgrowth assay. From these experiments, it can be concluded that the technique used in the present study is capable of immobilizing NGF onto GTG membranes covalently and remaining the bioactivity of NGF. Therefore, GEN composite can be materials for sustained release of bioactive NGF and a candidate for future therapeutic application in nerve repair.

Animals↗

PubMed2005

The self-setting properties and in vitro bioactivity of tricalcium silicate.

In this study, tricalcium silicate (Ca(3)SiO(5)), as a new promising injectable bioactive material, was employed to investigate its physical and chemical properties for an injectable bioactive cement filler. The workable Ca(3)SiO(5) pastes with a liquid to powder (L/P) ratio of 0.8--.2 mlg(-1)could be injected for 15--60 min (nozzle diameter 2.0mm). The setting process yielded cellular structures with compressive strength of 6.4--20.2 MPa after 2--28 days. The in vitro bioactivity of Ca(3)SiO(5) paste was investigated by soaking in simulated body fluid (SBF) for various periods. The result showed that the Ca(3)SiO(5) paste could induce hydroxyapatite (HA) formation and dissolve slowly in SBF. The result of indirect cytotoxicity evaluation indicated that Ca(3)SiO(5) paste had a stimulatory effect on cell growth in a certain concentration range. The exothermic process showed that Ca(3)SiO(5) had lower heat evolution rate during the hydration as compared to calcium phosphate cement (CPC). Our results indicated that Ca(3)SiO(5) paste was bioactive and dissolvable, and it is a progressive candidate for further investigation as injectable tissue repairing substitute.

Animals↗

PubMed2005

Optimising bioactive glass scaffolds for bone tissue engineering.

A 3D scaffold has been developed that has the potential to fulfil the criteria for an ideal scaffold for bone tissue engineering. Sol-gel derived bioactive glasses of the 70S30C (70 mol% SiO2, 30 mol% CaO) composition have been foamed to produce 3D bioactive scaffolds with hierarchical interconnected pore morphologies similar to trabecular bone. The scaffolds consist of a hierarchical pore network with macropores in excess of 500 microm connected by pore windows with diameters in excess of 100 microm, which is thought to be the minimum pore diameter required for tissue ingrowth and vasularisation in the human body. The scaffolds also have textural porosity in the mesopore range (10-20 nm). The scaffolds were sintered at 600, 700, 800 and 1000 degrees C. As sintering temperature was increased to 800 degrees C the compressive strength increased from 0.34 to 2.26 MPa due to a thickening of the pore walls and a reduction in the textural porosity. The compressive strength is in the range of that of trabecular bone (2-12 MPa). Importantly, the modal interconnected pore diameter (98 microm) was still suitable for tissue engineering applications and bioactivity is maintained. Bioactive glass foam scaffolds sintered at 800 degrees C for 2 h fulfill the criteria for an ideal scaffold for tissue engineering applications.

Biocompatible Materials↗

PubMed2005

Protein array consisting of sol-gel bioactive platform for detection of E. coli O157:H7.

Sol-gel-derived bioactive platform was fabricated for detection of pathogenic microbes, E. coli O157:H7. Design flexibility of sol-gel technique and ease of fabrication can fulfill to create the surfaces with structural and chemical features that are compatible with biomaterials such as antibody, enzymes, etc. In this study, the bioactive platform was prepared based on the silica gels, which were produced by hydrolyzing tetraethylorthosilane (TEOS) in ethanol. The mercaptopropyl triethoxysilane (MPTS) was mixed with the TEOS solution for the surface functionalization of bioactive platform. During TEOS hydrolysis, the modified thin film was prepared by sol-gel dip coating. Antibody against E. coli O157:H7 was immobilized with a configuration of protein array using piezo-type dispensing system. Surface morphology of the prepared bioactive platform was analyzed using atomic force microscopy (AFM). The antibody-antigen interaction was investigated with fluorescence microscopy and sandwich type immunoassay using fluorescein isothiocyanate (FITC)-labeled antibody. The results showed that antibody was sequestered within the sol-gel-derived bio-gel due to physical adsorption. The measurement of E. coli O157:H7 was done using the fabricated antibody surface. The fluorescence intensity was proportional to the concentration of E. coli O157:H7, of which the detection limit was 10(2)CFU/ml.

Antibodies, Monoclonal↗

PubMed2006

Nanocomposite containing bioactive peptides promote endothelialisation by circulating progenitor cells: an in vitro evaluation.

OBJECTIVE: The formation of an endothelial cell layer on the luminal surface of cardiovascular devices, especially bypass grafts, is an important attribute in order to improve their patency. Endothelial progenitor cells (EPCs) have a potential role in the endothelialisation of bypass grafts. We hypothesised that a novel approach to improve endothelialisation of bypass grafts by EPCs would be the creation on the graft lumen of a microenvironment that supports EPC adhesion and differentiation. METHODS: A new generation of nanocomposite based on silsesquioxane in the form of polyhedral oligomeric silsesquioxane (POSS) nanocages which incorporate bioactive peptides (RGD) was made into sheets. Peripheral blood mononuclear cells (PBMCs) containing EPCs isolated from six consenting young, healthy, adult volunteers were then plated both on (1) sheets of the nanocomposite with the bioactive peptide, (2) sheets of the nanocomposite without the bioactive peptide, (3) culture dishes as control and then cultured in presence of vascular endothelial growth factor (VEGF). Confirmation of endothelial and EPCs markers was carried out using fluorescence-activated cell sorter (FACS) analysis, reverse transcription polymerase chain reaction (RT-PCR) and immunostaining. RESULTS: One to two percent of PBMCs expressed CD34 as determined by FACS analysis. Cells were demonstrated to express mRNA for the EPC markers CD34, platelet-endothelial cell adhesion molecule-1 (CD31), CD133 and vascular endothelial growth factor receptor-2(FlK-1/KDR). Endothelial cell-colony forming units were formed between day 5 and day 7 after plating. Colonies were confirmed to be endothelial like cells by immunostaining. There were significantly greater numbers of EPC colonies on the bioactive nanocomposites as compared to the nanocomposite alone and the uncoated dishes. CONCLUSION: We report a new nanocomposite based biomaterial that has been demonstrated, in vitro, to promote endothelialisation from PBMCs containing EPCs.

Biocompatible Materials↗

PubMed2004

Binding of a monoclonal antibody positively correlates with bioactivity of the F4 fimbrial adhesin FaeG associated with post-weaning diarrhoea in piglets.

Piglets are susceptible to F4 (K88)+ enterotoxigenic Escherichia coli (ETEC)-induced neonatal and post-weaning diarrhoea. The F4 fimbriae are composed of some minor subunits and the major subunit FaeG that also constitutes the adhesin. Parenteral vaccination of sows with an F4-containing vaccine protects the suckling piglets against neonatal F4+ ETEC-induced diarrhoea, but no commercial (mucosal) vaccine exists against F4+ ETEC-induced weaning diarrhoea. To develop a vaccine, a bioactive F4-receptor (F4R) binding FaeG molecule is required that binds to the F4R following oral immunization and induces a FaeG-specific immune response. The present study reports the altered binding of the FaeG-specific monoclonal antibody IMM01 with bioactive versus non-bioactive F4 fimbrial adhesin FaeG. The correlation of altered IMM01 binding with altered FaeG bioactivity permits the use of an IMM01-based ELISA as a fast, specific and sensitive in vitro selection for potent F4 or (recombinant) FaeG antigen formulations, useful in an F4+ ETEC vaccine.

Adhesins, Escherichia coli↗

PubMed2006

Simultaneous quantification of three major bioactive triterpene acids in the leaves of Diospyros kaki by high-performance liquid chromatography method.

The leaf of Diospyros kaki, which is a traditional Chinese medicine, has been used for the treatment of various diseases. In order to improve the quality assurance of the leaves of D. kaki, derived extracts and phytomedicines, a simple, rapid and accurate high-performance liquid chromatography (HPLC) method was developed to simultaneously assess the three bioactive triterpene acids: barbinervic acid (BA) and its epimer, rotungenic acid (RA), along with 24-hydroxy ursolic acid (HA). This HPLC assay was performed on a reversed-phase C18 column with methanol and aqueous H3PO4 as the mobile phase and using a monitoring wavelength at 210 nm. This method was successfully applied to quantify these three bioactive triterpene acids in five different solvent extracts of the leaves of D. kaki and in the leaves from six different locations in China. The results demonstrated the total content and quantity of each of the main bioactive compounds were strongly dependent on the extraction solvents and locations, indicating that the quality control of the bioactive ingredients in the leaves of D. kaki, derived extracts and phytomedicines is critical to ensure its clinical benefits. The content of the total triterpenoids was also determined by the less selective colorimetric method, and the comparison with the HPLC method was given.

Calibration↗

PubMed2006

Screening and analysis of bioactive compounds in traditional Chinese medicines using cell extract and gas chromatography-mass spectrometry.

As the cost of drug development is always many times more than that of drug discovery, predictive methods aiding in the screening of bioavailable drug candidates are of profound significance. In this paper, a novel method for screening bioactive compounds from traditional Chinese medicines (TCMs) was developed by using living cell extract and gas chromatography (GC)-mass spectrometer (MS). The method was validated by using elemene emulsion injection (EEI), a typical TCM with known active compound, to interact with murine ascites hepatocarcinoma cell strain with high metastatic potential (HCa-F). Finally, the method was applied to screen the bioactive compounds from multi-component zedoary turmeric oil and glucose injection (ZTOGI). After HCa-F cells was incubated in ZTOGI, ethyl acetate (EtOAc) was used to extract the compounds in the cells for GC-MS analysis. Fourteen compounds were detected in the desorption eluate of HCa-F cell extract of ZTOGI, and further identified by MS. Curzerene and beta-elemene were found to be two major bioactive compounds in ZTOGI. These results show that the method developed may be applied to quickly screen the potential bioactive components in TCMs interacting with the target cells.

Animals↗

PubMed2004

BioPD: a web-based information center for bioactive peptides.

Bioactive peptide database (BioPD) is a web-based knowledge base that contains more than 1100 protein sequences from human, mouse and rat, which are putative or are known to be bioactive peptides. In addition to peptide sequences and the annotation, the database also contains gene sequences with annotation, protein interaction and disease data related to the peptides. Each entry has as many references as possible to support the information represented. BioPD consists of six parts: PROTEIN, GENE, DISEASE, LINKS, INTERACTION, and REFERENCE. The database is searchable through keyword, gene and protein name, receptor name, etc. The links to PDB, InterPro, Pfam, OMIM, etc. are provided in each entry. Thus BioPD is formed as an information center for the bioactive peptide and serves as a gateway for exploration of bioactive peptides. The database can be accessed at http://biopd.bjmu.edu.cn.

Animals↗

PubMed2002

Bioactive compounds in foods: their role in the prevention of cardiovascular disease and cancer.

"Bioactive compounds" are extranutritional constituents that typically occur in small quantities in foods. They are being intensively studied to evaluate their effects on health. The impetus sparking this scientific inquiry was the result of many epidemiologic studies that have shown protective effects of plant-based diets on cardiovascular disease (CVD) and cancer. Many bioactive compounds have been discovered. These compounds vary widely in chemical structure and function and are grouped accordingly. Phenolic compounds, including their subcategory, flavonoids, are present in all plants and have been studied extensively in cereals, legumes, nuts, olive oil, vegetables, fruits, tea, and red wine. Many phenolic compounds have antioxidant properties, and some studies have demonstrated favorable effects on thrombosis and tumorogenesis and promotion. Although some epidemiologic studies have reported protective associations between flavonoids or other phenolics and CVD and cancer, other studies have not found these associations. Various phytoestrogens are present in soy, but also in flaxseed oil, whole grains, fruits, and vegetables. They have antioxidant properties, and some studies demonstrated favorable effects on other CVD risk factors, and in animal and cell culture models of cancer. However, because phytoestrogens act both as partial estrogen agonists and antagonists, their effects on cancer are likely complex. Hydroxytyrosol, one of many phenolics in olives and olive oil, is a potent antioxidant. Resveratrol, found in nuts and red wine, has antioxidant, antithrombotic, and anti-inflammatory properties, and inhibits carcinogenesis. Lycopene, a potent antioxidant carotenoid in tomatoes and other fruits, is thought to protect against prostate and other cancers, and inhibits tumor cell growth in animals. Organosulfur compounds in garlic and onions, isothiocyanates in cruciferous vegetables, and monoterpenes in citrus fruits, cherries, and herbs have anticarcinogenic actions in experimental models, as well as cardioprotective effects. In summary, numerous bioactive compounds appear to have beneficial health effects. Much scientific research needs to be conducted before we can begin to make science-based dietary recommendations. Despite this, there is sufficient evidence to recommend consuming food sources rich in bioactive compounds. From a practical perspective, this translates to recommending a diet rich in a variety of fruits, vegetables, whole grains, legumes, oils, and nuts.

Antioxidants↗

PubMed1997

Circulating bioactive tumor necrosis factor-alpha, tumor necrosis factor-alpha receptors, fibronectin, and tumor necrosis factor-alpha inducible cell adhesion molecule VCAM-1 in uncomplicated pregnancy.

OBJECTIVES: Our goal was to assess in a longitudinal study of uncomplicated pregnancy the course of maternal plasma concentrations of the bioactive cytokine tumor necrosis factor-alpha, the soluble tumor necrosis factor-alpha receptors sTNFRI and sTNFRII, the soluble cell adhesion molecule sVCAM-1, and circulating fibronectin. STUDY DESIGN: Blood was collected from 22 healthy pregnant women at 7 to 17, 18 to 22, 23 to 28, and 30 to 36 weeks' gestation and post partum. Plasma samples were measured by bioassay for bioactive tumor necrosis factor-alpha, by immunoassay for sTNFRI, sTNFRII, and VCAM-1, and by radial immunodiffusion for circulating fibronectin, and data were statistically analyzed. RESULTS: Plasma concentrations of all variables were significantly linked with gestational age. Levels of bioactive tumor necrosis factor-alpha and sTNFRII showed a parallel rise in the second trimester and a decrease thereafter. Values for sTNFRI and sTNFRII and for these receptors and VCAM-1 were correlated, a weak correlation between bioactive tumor necrosis factor-alpha and sTNFRII was observed, and no correlation between circulating fibronectin and other variables was apparent. CONCLUSIONS: All variables studied exhibited a characteristic pattern depending on gestational age, which supports the concept of a physiologic role of tumor necrosis factor-alpha in pregnancy.

Adolescent↗

PubMed1990

Leuprolide acetate lowers circulating bioactive luteinizing hormone and testosterone concentrations during ovarian stimulation for oocyte retrieval.

Levels of immunoreactive luteinizing hormone (LH), bioactive LH, and testosterone (T) were determined in 52 women receiving human menopausal gonadotropins (hMG). In 26 women receiving leuprolide acetate (LA) preceding hMG, there was a significant suppression of immunoreactive LH and bioactive LH. The characteristic increase in serum levels of bioactive LH and T were absent. Follicular fluid estradiol and T concentrations, and serum progesterone were not different. The lower circulating levels of T may reflect reduced LH-stimulated androgen accumulation in smaller nonaspirated follicles and may account for the enhanced follicle recruitment observed during LA. The lack of premature luteinization despite marked rises of bioactive LH in the absence of LA is consistent with normal events during the menstrual cycle and was due to the early termination of hMG stimulation.

Chorionic Gonadotropin↗

PubMed1990

Effect of 20 alpha-dihydroxyprogesterone on the estrogen-induced bioactive luteinizing hormone surge in ovariectomized monkeys.

Progestins facilitate estrogen induction of the preovulatory luteinizing hormone (LH) surge. A biologically weaker progestin, 20 alpha-dihydroxyprogesterone, is reportedly increased at midcycle, but the importance of 20 alpha-dihydroxyprogesterone in regulating LH release has not been systematically studied. We therefore evaluated the effect of 2 doses of 20 alpha-dihydroxyprogesterone on the bioactive LH surge onset in ovariectomized monkeys. Chronically cannulated monkeys (n = 10) received estradiol (E2) benzoate (50 micrograms/kg) with and without subsequent 20 alpha-dihydroxyprogesterone injections (50 micrograms/kg, n = 3 and 100 micrograms/kg, n = 3). Blood was collected every 15 minutes over preselected intervals and the plasma assayed for bioactive LH and gonadal steroids. Low-dose 20 alpha-dihydroxyprogesterone administration resulted in periovulatory peripheral 20 alpha-dihydroxyprogesterone levels and did not advance the bioactive LH surge onset. In contrast, high-dose 20 alpha-dihydroxyprogesterone resulted in supraphysiological 20 alpha-dihydroxyprogesterone levels, slight increases in progesterone levels, and significant advancement of the surge over E2 benzoate treatment alone. We conclude that periovulatory levels of 20 alpha-dihydroxyprogesterone do not play a role in modulating the estrogen-induced bioactive LH surge.

Animals↗

PubMed1992

Follicle-stimulating hormone bioactivity in idiopathic normogonadotropic oligoasthenozoospermia: double-blind trial with gonadotropin-releasing hormone.

OBJECTIVE: To identify, among patients with idiopathic normogonadotropic oligoasthenozoospermia, those with low bioactive follicle-stimulating hormone (FSH), possibly because of inadequate gonadotropin-releasing hormone (GnRH) pulsatility, whose bioactive FSH and sperm could be improved by GnRH treatment. DESIGN: Randomized, double-blind, placebo-controlled trial with intranasal (IN) GnRH, followed by open GnRH treatment. SETTING: Outpatient endocrinology clinic. PATIENTS: Twenty-eight infertile men with idiopathic normogonadotropic oligoasthenozoospermia. INTERVENTIONS: Gonadotropin-releasing hormone or placebo was self-administered IN every 2 hours. MAIN OUTCOME MEASURES: Serum immunoreactive and bioactive FSH and semen analyses. RESULTS: Ten men showed a low basal FSH bioactive/immunoreactive ratio, which increased in 5 of them under GnRH without parallel sperm modification. Sperm improvements were observed in 10 patients with no parallel evolution of FSH bioactive/immunoreactive ratio. Unpredicted by sperm changes, three pregnancies developed on placebo and 5 on GnRH. CONCLUSIONS: Low bioactive FSH was not the cause of idiopathic normogonadotropic oligoasthenozoospermia in our patients and could not predict response to GnRH. Pulsatile GnRH did not improve sperm beyond random fluctuations.

Administration, Intranasal↗