Fenoldopam: effect on aldosterone secretion.
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Aldosterone↗
Biomedical subjects
J Smitz
Publications and source records attributed to J Smitz.
Effect of fenoldopam on the aldosterone response to metoclopramide in man.
The effect of fenoldopam, a selective DA1-agonist, on the plasma aldosterone response to metoclopramide was studied in six hypertensive patients included in a multicentre double-blind placebo controlled cross-over study of the antihypertensive effects of fenoldopam. Fenoldopam significantly increased baseline plasma renin activity (PRA); baseline plasma aldosterone levels rose slightly. Baseline PRL and the PRL response to metoclopramide were not altered by fenoldopam. After metoclopramide, a significant increase of plasma aldosterone was observed during treatment with fenoldopam, as well as in the placebo-period. The peak values were not significantly different and occurred at 15 min during both treatment periods. These results indicate that fenoldopam does not reduce metoclopramide-induced aldosterone secretion and therefore suggest that the adrenal dopamine receptor is not identical to the vascular DA1 receptor.
Aldosterone↗
Impact of ovarian stimulation on corpus luteum function and embryonic implantation.
The luteal phase has been found to be defective in virtually all the stimulation protocols used in in-vitro fertilization (IVF), indicating that common mechanisms might be involved despite the use of different drugs. A normal luteal phase is characterised by a normal hormonal environment, normal progesterone secretion by the corpus luteum and adequate endometrial secretory transformation. Luteinizing hormone supports the corpus luteum and luteal luteinizing hormone (LH) levels have been found to be reduced in human menopausal gonadotrophin (HMG), gonadotrophin-releasing hormone (GnRH)-agonist/HMG and GnRH-antagonist/HMG protocols, probably leading to an insufficient corpus luteum function. Supraphysiological steroid serum concentrations routinely observed in stimulated cycles may adversely affect LH secretion and induce a luteal-phase defect. In turn, these high steroid serum concentrations may advance early luteal-phase endometrial development leading to embryo-endometrial asynchrony and decreased pregnancy rates in IVF cycles.
Chorionic Gonadotropin↗
The role of vascular endothelial growth factor and interleukins in the pathogenesis of severe ovarian hyperstimulation syndrome.
Ovarian hyperstimulation syndrome (OHSS) is a dramatic complication of ovulation induction. In its most severe form, OHSS is characterized by massive cystic enlargement of the ovaries associated with third space fluid shift, resulting in the formation of ascites and pleural effusion. Ascites developes because of increased peritoneal capillary permeability. In this study we examined the role of vascular endothelial growth factor (VEGF) and interleukins in the pathogenesis of increased capillary permeability. VEGF is a member of the family of heparin binding proteins that act directly on endothelial cells to induce proliferation and angiogenesis. VEGF mRNA and protein are expressed by human ovarian granulosa and theca cells late in follicular development and subsequent to ovulation by granulosa and theca cells. Therefore, VEGF is ideally positioned to provoke the increased permeability of theca blood vessels that occurs shortly before ovulation. Hybridization studies in the rat and primate ovary have demonstrated VEGF mRNA expression predominantly after the luteinizing hormone (LH) surge known to be essential for OHSS. The gonadotrophin-releasing hormone antagonist results in a decreased mRNA expression, implying such expression is dependent on LH. The expression of VEGF mRNA has been recently shown to be enhanced by human chorionic gonadotrophin (HCG) in a dose- and time-dependent fashion. These studies confirm the timely association between VEGF and HCG that has been clinically known for many years to be integral in the development of OHSS. VEGF concentrations in serum, peritoneal fluid and follicular fluid of patients at risk for OHSS have been shown to be significantly related to the development of the syndrome. Furthermore, the kinetics of VEGF in the plasma of patients who actually develop severe OHSS are closely correlated with the clinical course of the syndrome and with certain biological characteristics of OHSS and of capillary leakage, such as leukocytosis and increased hematocrit. Studies on ascitic fluid from patients with sever OHSS have proved that VEGF is the major capillary permeability agent. Incubation with VEGF antiserum decreased the vascular permeability activity by 70%. Interleukin-2 (IL-2) is the first of a series of lymphocytotrophic hormones to be recognized as pivotal for the regulation of immune response. However, hard data to confirm its central role in the pathogenesis of OHSS are still lacking, despite the fact that some preliminary studies suggest a positive association between the pooled follicular fluid IL-2 concentration and the development of OHSS. IL-6 is a mediator of the acute phase response to injury, a systemic reaction characterized by leukocytosis, increased vascular permeability and increased synthesis of acute phase proteins by the liver. Significantly higher serum and ascites IL-6 concentrations were seen in OHSS patients. The immunohistochemical localization pattern suggested that IL-6 is LH or HCG dependent. However, the use of IL-6 as a predictor for the occurrence of OHSS has not been successful. The kinetics of IL-6 in patients with severe OHSS are correlated with the clinical symptoms and the biochemical parameters known to be associated with the severity of the syndrome, suggesting a possible role for IL-6. Further molecular biology studies similar to those performed on VEGF are needed to confirm if this interleukin is central in the cascade of events. IL-8 is a chemoattractant, activating cytokine and a potent angiogenic agent. The peritoneal fluid levels is increased in patients with severe OHSS; its concentration in peritoneal fluid is increased inpatients with severe OHSS. The place of this interleukin in the cascade of events is as yet undetermined and further studies are needed. In conclusion, molecular biology and clinical studies strongly suggest that VEGF is the principal mediator by which HCG might increase capillary permeability in OHSS.
Animals↗
Comparison between different routes of progesterone administration as luteal phase support in infertility treatments.
Different routes of natural progesterone supplementation have been tried as luteal phase support in infertility treatments. Orally administered progesterone is rapidly metabolized in the gastrointestinal tract and its use has proved to be inferior to i.m. and vaginal routes. Progesterone i.m. achieves serum progesterone values that are within the range of luteal phase and results in sufficient secretory transformation of the endometrium and satisfactory pregnancy rates. The comparison between i.m. and vaginal progesterone has led to controversial results as regards the superiority of one or the other in inducing secretory endometrial transformation. However, there is increasing evidence in the literature to favour the use of vaginal progesterone. Vaginally administered progesterone achieves adequate endometrial secretory transformation but its pharmacokinetic properties are greatly dependent on the formulation used. After vaginal progesterone application, discrepancies have been detected between serum progesterone values and histological endometrial features. Vaginally administered progesterone results in adequate secretory endometrial transformation, despite serum progesterone values lower than those observed after i.m. administration, even if they are lower than those observed during the luteal phase of the natural cycle. This discrepancy is indicative of the first uterine pass effect and therefore of a better bioavailability of progesterone in the uterus, with minimal systematic undesirable effects.
Administration, Intravaginal↗
Progesterone administration in patients with absent ovaries.
Forty-four women with absent ovaries who were referred to our centre for oocyte donation were treated with oestradiol valerate and natural progesterone. Serum concentrations and endometrial changes were evaluated on day 21 of stimulated luteal phases after the daily administration of 100 mg of natural progesterone in oil injected intramuscularly or after the ingestion of 300 mg of micronized progesterone or after vaginal administration of 300 mg or 600 mg micronized progesterone, respectively. Endometrial tissue did not show evidence of an adequate secretory pattern after orally administered progesterone. However, after intramuscular injection of 100 mg of natural progesterone and after the vaginal administration of 300 to 600 mg of micronized progesterone, the histologic and electron microscopic pictures were similar in all treatment groups and were close to the expected day 21 of the cycle. Serum levels of progesterone after intramuscular injection were five times higher than after vaginal administration.
Administration, Intravaginal↗
Quantification of eosinophil cationic protein and eosinophils in nasal secretions of allergen-induced nasal inflammation.
By using the microsuction technique, a quantitative determination of eosinophil cationic protein (ECP) in nasal secretions was performed in 18 atopic patients and 10 healthy volunteers. The percentage of the eosinophils was counted by simple microscopic examination. In the control group, results showed that the percentage of the eosinophils was almost 0 (range: 0-0.7%), and the median baseline ECP concentration was measured at 105 ng/g (range: 2-281 ng/g). No significant changes in either eosinophils or ECP were observed in this group. In the patient group, there existed a significantly higher baseline percentage of eosinophils (median: 2.7%, range: 0-45%) than in the control group but not for baseline ECP concentration (median: 160 ng/g, range: 6-1475 ng/g). One hour after nasal allergen challenge (NAC), a significant (P < 0.01) increase was seen in the percentage of eosinophils of the nasal secretions and this was remained for 10 hours (median: 5.5-13.3%). However, the difference that occurred was that ECP reached its highest concentration (median: 401 ng/g, range: 32-2298 ng/g) only 24 hours after NAC, while the percentage of the eosinophils decreased. Our findings again support a role of migration and activation of eosinophils in the pathogenesis of nasal allergic reaction, especially during the late phase.
Adolescent↗
A survey of four years of experience with intracytoplasmic sperm injection.
The present report covers the results of a 38-month period in which 2853 consecutive intracytoplasmic sperm injection (ICSI) cycles were performed in 1953 couples. These couples were afflicted with male factor infertility and had at least one previous failed conventional in vitro fertilization (IVF) treatment cycle. In other couples, the husband had semen parameters incompatible with conventional IVF or suffered from excretory or secretory azoospermia where it was possible to recover spermatozoa by microsurgical epididymal sperm aspiration (mesa) or by testicular sperm extraction (tese) procedure. Overall, the 2-PN fertilization rate was 62% per retrieved metaphase II oocyte and 70% per successfully injected metaphase II oocyte. Embryo transfer was performed in 91% of started cycles. The cumulative pregnancy rate (positive HCG) was 34% per started ICSI treatment and 37% per embryo transfer.
Adult↗
Azoospermia and intracytoplasmic sperm injection.
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Biopsy, Needle↗