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Biomedical subjects

M A Palumbo

Publications and source records attributed to M A Palumbo.

At least 19 recordsLinked to original sources

Umbilical cord serum activin A levels are increased in pre-eclampsia with impaired blood flow in the uteroplacental and fetal circulation.

The aims of the present study were to evaluate the umbilical cord serum activin A concentrations in complicated pregnancies and also to explore the relationship between activin A levels and blood flow velocity in fetal arteries. Umbilical cord blood samples were obtained postpartum after a full term uneventful gestation (control group, n=40), and from pregnancies complicated by gestational diabetes (n=13), preterm labour (n=18), or pre-eclampsia (n=19). Cord serum activin A levels were three-fold higher in pregnancies complicated by pre-eclampsia (1.17+/-0.14 ng/ml, p<0.01) than in the control group (0.43+/-0.03 ng/ml), but were unaltered in the diabetes and preterm labour groups. The pre-eclampsia group had a marked increase of umbilical artery pulsatility index (PI) and also a decrease of middle cerebral artery PI (p<0.01). Furthermore, activin A concentration correlated directly with the umbilical artery PI (r=0.540, p=0.021), with the length of stay in the Neonatal Intensive Care Unit (r=0.857, p<0.001) and also with cord blood pH (r=-0.886, p<0.001). In conclusion, umbilical cord serum activin A levels are increased in the presence of pre-eclampsia and provide an indirect marker of impaired blood flow in the uteroplacental and fetal circulation.

Activins↗

Pre-eclampsia with fetal growth restriction: placental and serum activin A and inhibin A levels.

Activin A (beta A beta A) and inhibin A (alpha beta A) are dimeric glycoproteins secreted from early to term pregnancy in the maternal circulation. They circulate in higher amounts in women with gestational hypertension and/or pre-eclampsia, the most important gestational diseases also causing fetal growth restriction (FGR). Since no data are available in patients with pre-eclampsia and superimposed FGR, by using two-site immunoassays we evaluated serum activin A and inhibin A levels in serum samples collected from: healthy normotensive pregnant controls (n = 42); and women with pre-eclampsia with (n = 19) or without superimposed FGR (n = 21). In addition, by quantitative reverse transcriptase-polymerase chain reaction the changes of alpha- and beta A-subunit mRNA expression in placentas collected from healthy controls (n = 7) and pre-eclamptic pregnancies with (n = 6) or without (n = 6) superimposed FGR was also investigated. Activin A and inhibin A serum levels were significantly higher in pre-eclampsia, and the presence of FGR did not significantly modify these concentrations. Similarly, inhibin-subunit mRNA levels in placentas from pre-eclampsia were significantly higher than in controls, and FGR did not significantly affect this expression. The present data suggest that the increased placental expression of inhibin subunit mRNAs is part of the mechanism leading to increased serum activin A and inhibin A levels.

Activins↗

Surgical treatment of thoracic spinal stenosis: a 2- to 9-year follow-up.

STUDY DESIGN: A retrospective investigation of the results of operative treatment of patients with symptomatic thoracic spinal stenosis. OBJECTIVES: To establish the effectiveness and define the limitations of surgical treatment for stenosis of the thoracic spinal canal. SUMMARY OF BACKGROUND DATA: In contrast to cervical and lumbar stenosis, symptomatic narrowing of the thoracic spinal canal is rarely encountered. Although the treatment of thoracic stenosis has been described in multiple case reports and in several small series with minimal follow-up evaluation, there are few studies of patients treated surgically for this condition with follow-up evaluation beyond 2 years. METHODS: Twelve patients who underwent operative decompression for symptomatic stenosis of the lower thoracic spine were followed up for an average period of 62.4 months. Surgery was performed on the thoracic spine alone in four cases and on the combined thoracolumbar spine in eight. Factors that were investigated included pain severity, lower extremity motor function, ambulatory status, and postoperative complications. RESULTS: The level of pain after surgery was decreased in eight patients and unchanged in four patients. Of the 10 patients with a motor deficit before surgery, eight had improvement of muscle function. Of the 11 patients with a gait disturbance before surgery, ambulatory status was improved in seven, unchanged in two, and worse in two. One patient lost neural function secondary to surgical intervention. There were five cases in which the early result subsequently deteriorated because of recurrent stenosis, spinal deformity/instability, or both. CONCLUSIONS: Thoracic stenosis can occur in isolation or, more commonly, in association with lumbar stenosis. Ideally, operative treatment should address all stenotic segments and directly decompress the primary anatomic abnormalities causing neural element compression. Although satisfactory short-term results can be expected, deterioration of the early outcome because of the potential for recurrent stenosis and deformity/instability at the thoracolumbar junction can sometimes be seen with longer follow-up evaluation periods.

Adult↗

Diagnosing basilar invagination in the rheumatoid patient. The reliability of radiographic criteria.

BACKGROUND: Basilar invagination can be difficult to diagnose with plain radiography in patients with rheumatoid arthritis. Although numerous radiographic criteria have been described, few studies have addressed the reliability of these parameters in the rheumatoid population. The purpose of the present study was to validate and compare the most widely accepted plain radiographic criteria for basilar invagination in this patient population. METHODS: Cervical radiographs of 131 rheumatoid patients were examined. Of these patients, sixty-seven (twenty-nine with basilar invagination and thirty-eight without it) were also evaluated with tomograms, magnetic resonance imaging, and/or sagittally reconstructed computed tomography scans to detect the presence of basilar invagination. Three observers who were blinded with regard to the diagnosis independently scored each radiograph as positive, negative, or indeterminate according to the established criteria for invagination proposed by Clark et al., McRae and Barnum, Chamberlain, McGregor, Redlund-Johnell and Pettersson, Ranawat et al., Fischgold and Metzger, and Wackenheim. Interobserver and intraobserver variability, sensitivity, specificity, total percentage of correct results, and negative and positive predictive values were determined for each criterion as well as for various combinations of the criteria. RESULTS: No single test had a sensitivity and a negative predictive value of greater than 90% as well as a reasonable specificity and a reasonable positive predictive value. The combination of the Clark station, the Redlund-Johnell criterion, and the Ranawat criterion, scored as positive for basilar invagination if any of the three were positive, proved to be better than any single criterion; the sensitivity of the combined criteria was 94%, and the negative predictive value was 91%. CONCLUSIONS: A screening test for basilar invagination should have a high sensitivity and a high negative predictive value, so that the disease will not be missed, and yet be specific, so that the disease will not be overdiagnosed. Our data suggest that none of the widely utilized plain radiographic criteria meet these goals. We recommend that measurements be made according to the methods described by Clark et al., Redlund-Johnell et al., and Ranawat et al. and, if any of these suggests basilar invagination, tomography or magnetic resonance imaging should be performed. Since approximately 6% of the cases of basilar invagination in rheumatoid patients would still be missed with this approach, tomography or magnetic resonance imaging should be performed on a rheumatoid patient whenever plain radiographs leave any doubt about the diagnosis of basilar invagination.

Adult↗

Impact of smoking on the outcome of anterior cervical arthrodesis with interbody or strut-grafting.

BACKGROUND: An increased rate of pseudarthrosis has been documented following posterolateral lumbar spine grafting in patients who smoke. This same relationship has been assumed for anterior cervical interbody grafting, but to our knowledge it has never been proven. This study compared the long-term radiographic and clinical results of smokers and nonsmokers who had undergone arthrodesis with autogenous bone graft following multi-level anterior cervical decompression for the treatment of cervical radiculopathy or myelopathy, or both. METHODS: One hundred and ninety patients were followed clinically and radiographically for at least two years (range, two to fifteen years). Fifty-nine of the patients had corpectomy with strut-grafting, and 131 patients had multiple discectomies and interbody grafting. Fifty-five of the 190 patients had a history of active cigarette-smoking; fifteen of the fifty-five had corpectomy with strut-grafting, and forty had multilevel discectomies and interbody grafting. Internal fixation was not used in any patient. The reconstruction techniques and postoperative bracing regimen were similar between smokers and nonsmokers. Osseous union was judged on dynamic lateral radiographs made at least two years following surgery, and clinical outcomes were judged on the basis of pain level, medication usage, and daily activity level. RESULTS: Of the forty smokers who had undergone multilevel interbody grafting, twenty had a solid fusion at all levels, whereas sixty-nine of the ninety-one nonsmokers had solid fusion at all levels (p < 0.02; chi-square test). This difference was especially pronounced among patients who had had a two-level interbody grafting procedure (p < 0.002; chi-square test). With the numbers available, there was no difference in the rate of fusion between smokers (fourteen of fifteen) and nonsmokers (forty-one of forty-four) who had undergone corpectomy and strut-grafting, as 93% of both groups had a solid union. In addition, clinical outcomes were significantly worse among smokers when compared with nonsmokers (p < 0.03; rank-sum analysis). CONCLUSIONS: Smoking had a significant negative impact on healing and clinical recovery after multilevel anterior cervical decompression and fusion with autogenous interbody graft for radiculopathy or myelopathy. Since smoking had no apparent effect upon the healing of autogenous iliac-crest or fibular strut grafts, subtotal corpectomy and autogenous strut-grafting should be considered when a multilevel anterior cervical decompression and fusion is performed in patients who are unable or unwilling to stop smoking prior to surgical treatment.

Bone Transplantation↗

Radiculopathy and myelopathy at segments adjacent to the site of a previous anterior cervical arthrodesis.

BACKGROUND: We studied the incidence, prevalence, and radiographic progression of symptomatic adjacent-segment disease, which we defined as the development of new radiculopathy or myelopathy referable to a motion segment adjacent to the site of a previous anterior arthrodesis of the cervical spine. METHODS: A consecutive series of 374 patients who had a total of 409 anterior cervical arthrodeses for the treatment of cervical spondylosis with radiculopathy or myelopathy, or both, were followed for a maximum of twenty-one years after the operation. The annual incidence of symptomatic adjacent-segment disease was defined as the percentage of patients who had been disease-free at the start of a given year of follow-up in whom new disease developed during that year. The prevalence was defined as the percentage of all patients in whom symptomatic adjacent-segment disease developed within a given period of follow-up. The natural history of the disease was predicted with use of a Kaplan-Meier survivorship analysis. The hypothesis that new disease at an adjacent level is more likely to develop following a multilevel arthrodesis than it is following a single-level arthrodesis was tested with logistic regression. RESULTS: Symptomatic adjacent-segment disease occurred at a relatively constant incidence of 2.9 percent per year (range, 0.0 to 4.8 percent per year) during the ten years after the operation. Survivorship analysis predicted that 25.6 percent of the patients (95 percent confidence interval, 20 to 32 percent) who had an anterior cervical arthrodesis would have new disease at an adjacent level within ten years after the operation. There were highly significant differences among the motion segments with regard to the likelihood of symptomatic adjacent-segment disease (p<0.0001); the greatest risk was at the interspaces between the fifth and sixth and between the sixth and seventh cervical vertebrae. Contrary to our hypothesis, we found that the risk of new disease at an adjacent level was significantly lower following a multilevel arthrodesis than it was following a single-level arthrodesis (p<0.001). More than two-thirds of all patients in whom the new disease developed had failure of nonoperative management and needed additional operative procedures. CONCLUSIONS: Symptomatic adjacent-segment disease may affect more than one-fourth of all patients within ten years after an anterior cervical arthrodesis. A single-level arthrodesis involving the fifth or sixth cervical vertebra and preexisting radiographic evidence of degeneration at adjacent levels appear to be the greatest risk factors for new disease. Therefore, we believe that all degenerated segments causing radiculopathy or myelopathy should be included in an anterior cervical arthrodesis. Although our findings suggest that symptomatic adjacent-segment disease is the result of progressive spondylosis, patients should be informed of the substantial possibility that new disease will develop at an adjacent level over the long term.

Adolescent↗

Anterior cervical corpectomy in patients previously managed with a laminectomy: short-term complications.

BACKGROUND: The purpose of this study was to evaluate the complications of anterior cervical corpectomy and arthrodesis in patients who had had a previous cervical laminectomy. The results of previous studies have suggested that these patients can be managed with anterior decompression and an arthrodesis with either plate fixation or immobilization in a halo vest. However, no studies that we are aware of have specifically focused on the complications of these types of procedures. METHODS: The records and radiographs of eighteen patients who had been managed with a one to four-level corpectomy with strut-grafting were retrospectively reviewed. The reviews were independently performed by the three of us who were not involved in the original operation. The interval between the laminectomy and the corpectomy ranged from one month to twenty-two years (mean, eight years). RESULTS: Eleven of the eighteen patients sustained a total of sixteen complications during the follow-up period, which averaged 2.7 years (range, seven months to six years and four months), and nine of the eleven had graft-related complications. Five grafts extruded or collapsed, or both. There were four reoperations. Immobilization in a halo vest did not prevent extrusions, as three of the four extrusions occurred while the patient wore a halo vest. Four patients had a pseudarthrosis. In three patients, the kyphosis increased by 10 degrees or more from the immediate preoperative period to the most recent follow-up evaluation. Two patients had respiratory distress that necessitated reintubation, one patient had a small dural tear, and one had transient dysphagia. CONCLUSIONS: Our data suggest that anterior cervical corpectomy without instrumentation in a patient who has had a previous laminectomy is associated with a great risk of graft-related complications despite the use of a halo vest. This previously unreported finding is relevant in that it contradicts the recommendation previously made by Zdeblick and the senior one of us, who advocated postoperative immobilization in a halo vest for these patients. Anterior cervical corpectomy should be performed with caution and knowledge of the potential complications in a patient who has had a previous laminectomy.

Adult↗

Macrophage-derived cytokines in the follicular fluids of women with infertility due to immunological causes. Elevated levels of interleukin 6 and low levels of granulocyte-macrophage colony-stimulating factor.

The cytokines are (glyco)proteins secreted by lymphoid and non-lymphoid cells which modulate several biological responses including the ovarian function. Interleukin (IL)-1 and tumour necrosis factor (TNF)-alpha suppress 17beta-estradiol (E2) and progesterone release from granulosa and luteal cells in vitro. TNF-alpha affects negatively folliculogenesis and ovarian maturation. Additional in vivo evidence for a role of this macrophage-derived cytokine came from our recent observation that women with infertility due to immunological causes have elevated intrafollicular fluid levels of TNF-alpha and decreased levels of E2 compared to women with a tubal factor of infertility. Because the macrophages are a primary component of the intrafollicular compartment, the present study was undertaken to evaluate whether other macrophage-derived cytokines are also released in the human follicular fluid. To accomplish this, we measured the levels of IL-1beta, IL-6, IL-10 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the follicular fluids of two groups of infertile women undergoing to an in vitro fertilization program. The first group of women had a significant titre of anti-spermatozoon antibodies in the serum and/or the mucus as the only cause of infertility, whilst the second group of women was infertile because of non patent fallopian tubes. Intrafollicular cytokines levels were measured by solid-phase ELISA and steroid concentrations by radioimmunoassay. Whilst IL-1beta, IL-6, IL-10, and GLM-CSF were all measurable in the follicular fluid of both groups of women, the levels of IL-6 were found to be significantly more elevated and those of GM-CSF lower in patients with infertility due to immunological causes as compared to those with tubal infertility. The former had also decreased intrafollicular E2 levels and increased progesterone concentrations. No difference was seen in the follicular fluid levels of testosterone and androstenedione. In conclusion, several macrophage-derived cytokines are present in the follicular fluids of infertile women. Patients with infertility due to immunological causes had higher levels of IL-6 and lower concentrations of GM-CSF as compared to patient with a tubal factor of infertility. We speculate that this abnormal cytokine profile may contribute to the altered intrafollicular steroid milieu.

Adult↗

Emergency removal of football equipment: a cadaveric cervical spine injury model.

STUDY OBJECTIVE: To determine the influence of football helmet and shoulder pads, alone or in combination, on alignment of the unstable cervical spine. METHODS: The alignment of the intact cervical spine in 8 cadavers was assessed radiographically under 4 different football equipment conditions: (1) no equipment, (2) helmet only, (3) helmet and shoulder pads, and (4) shoulder pads only. Each specimen was then surgically destabilized at C5-C6 to simulate a flexion-distraction injury. Repeat radiographs were obtained under the same 4 equipment conditions, and alignment of the unstable segment was analyzed. RESULTS: Before the destabilization, neutral alignment was maintained when both helmet and shoulder pads were in place. The "helmet only" condition caused a significant decrease in lordosis (mean, 9.6 +/- 4.7 degrees), whereas the "shoulder pads only" condition caused increased lordosis (13.6 +/- 6.3 degrees). After destabilization, the "helmet-only" condition demonstrated significant mean increases in C5-C6 forward angulation (16.5 +/- 8.6 degrees), posterior disc space height (3.8 +/- 2.3 mm), and dorsal element distraction (8.3 +/- 5.4 mm). CONCLUSION: Our flexion-distraction model demonstrated that immobilization of the neck-injured football player with only the helmet in place violates the principle of splinting the cervical spine in neutral alignment. By extrapolation to an extension-type injury, immobilization with only the shoulder pads left in place similarly violates this principle. In order to maintain a neutral position and minimize secondary injury to the cervical neural elements, the helmet and shoulder pads should be either both left on or both removed in the emergency setting.

Aged↗

The neuroactive steroid allopregnanolone suppresses hypothalamic gonadotropin-releasing hormone release through a mechanism mediated by the gamma-aminobutyric acidA receptor.

The central nervous system (CNS) is able to synthesize and/or metabolize steroid hormones. These neuroactive steroids are capable of modulating several brain functions and, among these, they seem to regulate the hypothalamic-pituitary-gonadal (HPG) axis. Indeed, recent observations have shown that 5 alpha-pregnane-3 alpha-ol-20-one (allopregnanolone), one of the most abundant naturally occurring neuroactive steroids, suppresses ovulation and sexual behaviour when administered within the CNS. The present study was undertaken to evaluate the effects of allopregnanolone and its inactive stereoisomer, 5 alpha-pregnane-3 beta-ol-20-one, upon the release of gonadotropin-releasing hormone (GnRH) from individually-incubated hemihypothalami. Allopregnanolone suppressed GnRH release in a concentration-dependent manner with maximal activity in the nanomolar range, a range at which this neurosteroid is capable of playing a biological action. The specificity of allopregnanolone suppression of GnRH release was provided by the lack of effect of its known inactive stereoisomer. To evaluate the involvement of gamma-aminobutyric acidA (GABAA) receptor, we examined the effects of two neurosteroids with GABA-antagonistic properties, pregnanolone sulfate (PREG-S) and dehydroepiandrosterone sulfate (DHEAS), and of bicuculline, a selective antagonist of the GABA binding site on the GABAA receptor, on allopregnanolone (10 nM)-suppressed GnRH release. Both PREG-S and bicuculline overcame the inhibitory effects of allopregnanolone on GnRH release, whereas DHEAS did not. To substantiate the involvement of the GABAA receptor further, we tested the effects of muscimol, a selective agonist for this receptor, which suppressed GnRH release. In conclusion, allopregnanolone suppressed hypothalamic GnRH release in vitro and this effect appeared to be mediated by an interaction with the GABAA receptor. We speculate that the inhibitory effect of allopregnanolone on the HPG axis may also be caused by its ability to suppress hypothalamic GnRH release.

Animals↗

Induction of ovulation in thalassemic patients.

The authors studied 19 thalassemic patients: 14 patients with secondary amenorrhea (group A), 5 patients with primary amenorrhea (group B) and 1 patient with anovulation (group C). All the patients underwent three cycles of induction of ovulation with FSH. The level of 17 beta-estradiol and the diameter of follicles were evaluated every three days. Normal gonadal function was maintained in three patients with positive response at Step 1 of the treatment.

Amenorrhea↗

Osteopenia in female beta-thalassemic patients.

Sixty-four women with thalassemia major aged 13-28 years were studied. 49 patients had primary amenorrhea and 15 had secondary amenorrhea. Bone density of the spine was performed using lunar DPX. The Z score was used to evaluate the degree of osteopenia. In 82% of the patients a Z score less than -2 was found. BMD correlated negatively with the duration of amenorrhea and age of thalassemic patients.

Absorptiometry, Photon↗

Relationship between tumour necrosis factor alpha and sex steroid concentrations in the follicular fluid of women with immunological infertility.

Experimental evidence suggests a tight relationship between cytokines and the reproductive system. Tumour necrosis factor alpha (TNF alpha), a cytokine produced by activated macrophages and mesenchymal cells, seems to participate in the control of fertility. Therefore, the present study was undertaken to evaluate the concentrations of TNF alpha in the follicular fluid of female patients with immunological infertility, as well as the possible role of this cytokine in follicular development. Concentrations of TNF alpha, 17 beta-oestradiol, progesterone, androstenedione and testosterone were measured in the follicular fluid of patients with immunological infertility and patients with a tubal factor of infertility, who served as a control group. Patients with immunological infertility had significantly higher concentrations of TNF alpha in their follicular fluid compared to the control group. In contrast, oestradiol concentrations were significantly lower in the former group. The intrafollicular concentrations of the other steroids measured did not differ significantly between the two groups. The fertilization rate of ova from follicles included in the study was significantly lower in patients with immunological infertility compared to control subjects (19.1 and 57.1% respectively). In conclusion, this study shows that patients with infertility of immunological origin have increased follicular fluid concentrations of TNF alpha and lower oestradiol concentrations. We speculate that elevated TNF alpha concentrations in the human follicle may negatively influence both ovulation-and fertilization-related events.

Adult↗

Effects of corticotropin-releasing hormone on ovarian estrogen production in vitro.

It is a common clinical observation that stress is accompanied by dysfunction of the hypothalamic-pituitary-ovarian axis, and there is mounting experimental evidence that CRH, the principal regulator of ACTH release and the central coordinator of the stress response, is able to suppress gonadal function by inhibiting hypothalamic GnRH release. Recently, it has been shown that immunoreactive CRH, CRH messenger RNA, and CRH receptors are also present in the ovary. This prompted us to examine the role of CRH on ovarian function. To accomplish this, we studied the effects of this neuropeptide on estrogen production and cAMP intracellular content from rat granulosa and human granulosa-luteal cells. We also evaluated the activity of the enzyme aromatase by measuring the production of tritiated water from homogenates of cultured rat granulosa cells. CRH inhibited FSH-stimulated estrogen production from rat granulosa cells in a dose-dependent fashion. The maximal effect was achieved at a concentration of 10(-8) M, which suppressed estrogen production by about 30%. Low concentrations of CRH (10(-10) M), incapable of modulating maximal estrogen production in response to FSH, provoked a right-ward shift of the estrogen dose-response curve to FSH. CRH (10(-8) M) suppressed the production of tritiated water (equivalent to estrogen production) from homogenates of rat granulosa cells incubated with a half-maximal concentration of FSH. Basal estrogen production by human granulosa-luteal cells was also inhibited by CRH at a concentration of 10(-10) M. The maximal effect was achieved with a concentration of 10(-8) M, which lowered estrogen production by 25%. The CRH receptor antagonist alpha-helical CRH-(9-41) antagonized the inhibitory effect of CRH on estrogen production from rat granulosa and human granulosa-luteal cells, whereas alone it had no effect. CRH did not have any effect on the intracellular cAMP content of rat granulosa and human granulosa-luteal cells. In conclusion, these results suggest that CRH is able to suppress estrogen production from rat and human granulosa cells in vitro. This effect seems to be linked to inhibition of aromatase activity in the rat and is independent of cAMP generation. We speculate that CRH may also interfere with hypothalamic-pituitary-gonadal axis function by acting directly at the ovarian level.

Animals↗

Allopregnanolone concentration in hippocampus of prepubertal rats and female rats throughout estrous cycle.

Hippocampus plays an important role in cognition, neuroendocrine function and sexual behaviour. Changes of hippocampal neuropeptide and neurotransmitter concentrations are associated to behavioural changes occurring throughout reproductive life. The present study focused the attention on the presence of a neurosteroid, 5 alpha-pregnan-3 alpha-ol-20-one (termed allopregnanolone) in hippocampus. In particular, hippocampal allopregnanolone concentration in male and female prepubertal rats and in female rats throughout estrous cycle were evaluated. Hippocampal extracts were eluted on high pressure liquid chromatography and allopregnanolone concentration was measured by radioimmunoassay. Prepubertal male and female rats (15 days old) showed highest values which significantly decreased with advancing age (25 and 60 days) (p < 0.01); the lowest hippocampal concentration of allopregnanolone was found in adult rats. Female rats on proestrus morning and afternoon showed an hippocampal allopregnanolone concentration significantly higher than on diestrus or on estrus (p < 0.01), while rats on estrus showed hippocampal allopregnanolone concentration significantly lower than during other days of estrus cycle (p < 0.01). These data indicate differences in hippocampal concentration of allopregnanolone between prepubertal and adult rats and throughout estrous cycle in female rats. This finding suggest a putative role of neurosteroids in the modulation of behavioral changes occurring throughout reproductive life.

Animals↗

Steroid-protein interaction in human placenta.

Human placenta produces a large variety of bioactive substances with endocrine and neural competence: pituitary and gonadal hormones, hypothalamic-like releasing or inhibiting hormones, growth factors, cytokines and neuropeptides. The most recent findings indicate that locally produced hormones regulate the secretion of other placental hormones supporting a paracrine/autocrine regulation. In placental endocrinology, a particular relevance is played by steroid hormones. In fact, a specific gonadotropin-releasing hormone (GnRH)-human chorionic gonadotropin (hCG) regulation of placental steroidogenesis has been proposed as a placental internal regulatory system acting on steroids production from human placenta. In addition, activin and inhibin have been proposed as further regulatory substances of the synthesis and secretion of steroids; the addition of activin A to placental culture augments GnRH, hCG and progesterone, and this effect can be significantly reduced by the addition of inhibins. Finally, a steroid-steroid interaction is suggested by the evidence that placental estrogen has a positive role in the regulation of progesterone biosynthesis. Other steroid-protein interactions have been observed in human placenta. In fact, recent data indicate that progesterone inhibits placental corticotropin-releasing factor (CRF) and estrogens act on placental conversion of cortisol to cortisone, activating cortisol secretion by the fetal adrenal and enhancing fetal adrenal function with advancing gestation.

Animals↗

Clinical and endocrine effects of finasteride, a 5 alpha-reductase inhibitor, in women with idiopathic hirsutism.

OBJECTIVE: To evaluate the effects of long-term administration of finasteride on hirsutism score, basal gonadotropin, and androgen secretion in women with idiopathic hirsutism. DESIGN: Randomized single-blinded study. PATIENTS: Eighteen patients with moderate-severe hirsutism were recruited for the study. INTERVENTIONS: Nine hirsute patients received 7.5 mg/d oral finasteride for a period of 9 months whereas the other nine were treated with placebo. Hirsutism score, serum basal gonadotropin, androgens, estrogen, and sex hormone-binding globulin (SHBG) levels were evaluated in all patients before treatment and every 3 months during treatment. RESULTS: After 6 and 9 months of treatment, the hirsutism score improved significantly in the patients receiving finasteride, whereas no significant modifications were observed in patients treated with placebo. The side effects observed were headache and depression of modest entity during the 1st month of treatments, whereas libido did not change. Serum levels of LH, FSH, androstenedione, unbound T, DHEAS, E2, 17 alpha-hydroxyprogesterone, and SHBG did not change during therapy. Hirsute patients treated with finasteride exhibited a marked decrease of dihydrotestosterone and a significant increase of T serum levels from the 3rd and 6th months of treatment, respectively. CONCLUSION: Finasteride decreased the hirsutism score of patients affected by idiopathic hirsutism with few side effects during treatment. No modification of libido was observed.

5-alpha Reductase Inhibitors↗