Soy isoflavones, inulin, calcium, and vitamin D3 in post-menopausal hot flushes: an observational study.

Purpose of investigation To evaluate the effect of soy isoflavones and inulin (SII) on hot flushes (HF) and quality of life in a clinical setting, the authors conducted an observational study. Materials and methods The authors performed an observational, prospective, multicentric study on women in peri-/post-menopause treated or untreated with a product present on the Italian market, consisting in a mixture of calcium (500 mg), vitamin D3 (300 IU), inulin (3 g) and soy isoflavones (40 mg). Results A total of 135 patients, 75 (55.6%) in the SII group and 60 (44.4%) in the untreated group entered the study. After three months, the mean number of HF declined of 2.8 (SD 3.7) in the SII group and 0.0 in the untreated one. The corresponding values after six months were -3.7 (SD 2.7) in the SII group and -0.9 (SD 5.3) in the control group (p = 0.02). Conclusion This observational trial suggests a possible beneficial effect of a dietary soy supplement containing 40 mg of isoflavone/day plus inulin in the management of menopausal symptoms such as hot flashes

Contraception as prevention and therapy: sex steroids and the brain.

The brain is one of the specific target tissues for sex steroid hormones. Estrogens, progestins and androgens are able to induce several effects in brain areas of the central nervous system (CNS), through the binding with specific receptors. Specific receptors for gonadal steroids have been identified in the amygdala, hippocampus, basal forebrain cortex, cerebellum, locus ceruleus, midbrain rafe nuclei, glial cells, pituitary gland, hypothalamus and central gray matter. At the hypothalamic level, the principal target for sex steroids is those neurons producing the pulsatile release of the gonadotropin releasing hormone (GnRH), localized in the mediobasal hypothalamus and the arcuate nucleus. The GnRH release depends on the complex and co-ordinated interrelationships among gonadal steroids, pituitary gonadotropins and neuroactive transmitters, such as the noradrenaline, dopamine, opioid peptides (beta-endorphin), acetylcholine, serotonin, gamma-aminobutyrric acid, corticotropin releasing hormone and neuropeptide Y. The interplay of these control mechanisms is governed by peripheral feedback signals; as well as the input from higher brain centers they may modify the GnRH secretion. The anterior pituitary lobe is the best known target tissue for endogenous or exogenous sex steroid hormones, because it is possible to detect luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in blood, as the expression of the pituitary cells' activity. The synthesis and release of FSH and LH by the gonadotropic cells depend upon the peripheral control of gonadal hormones and the GnRH hypothalamic release. In summary, during a woman's reproductive life, the interaction between neurotransmitters, neuropeptides and gonadal hormones modulates the hypothalamo-pituitary-gonadal axis by acting selectively on the synthesis and release of GnRH and of pituitary gonadotropic hormones. The increased use of oral contraceptives in the last 30 years and, in general, of sex steroid hormone derivative therapies, has led to the study of the biochemical and metabolic properties of the different progestin molecules available in hormonal therapies by focusing attention on the interactions between estrogens and progestins in the modulation of the hypothalamo-pituitary-gonadal axis. The different kinds of estrogen and progestin molecules used in oral contraceptives inhibit the ovulatory process and may interfere with other sex steroid hormone receptors, thus exerting multiple effects in each target tissue

CNS: SEX STEROIDS AND SERMS

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Effects of the new generation selective estrogen receptor modulator EM-652 and oral administration of estradiol valerate on circulating, brain, and adrenal beta-endorphin and allopregnanolone levels in intact fertile and ovariectomized rats.

OBJECTIVE: To investigate the effects of oral estradiol valerate (EV); EM-652, a new-generation selective estrogen receptor modulator; and both agents on central and peripheral beta-endorphin (beta-EP) and allopregnanolone levels in fertile and ovariectomized rats. DESIGN: Prospective study. SETTING: Animal laboratory in an academic research environment. ANIMALS: Thirteen groups of eight Wistar female rats received oral EV (0.01 or 0.05 mg/kg of body weight daily), EM-652 (0.1, 1, or 5 mg/kg daily), or EV (0.05 mg/kg daily) and EM-652 (0.1, 1, or 5 mg/kg/daily) for 14 days. INTERVENTION(S): beta-Endorphin levels content in the hypothalamus, hippocampus, anterior and neurointermediate pituitary, and plasma were measured. Allopregnanolone levels in the hypothalamus, hippocampus, anterior pituitary, adrenal glands, and serum were measured. MAIN OUTCOME MEASURE(S): beta-Endorphin and allopregnanolone levels. RESULT(S): In ovariectomized rats, administration of EV or EM-652 reverses changes in beta-EP and allopregnanolone levels induced by ovariectomy. Administration of EM-652 plus EV prevents the increase in beta-EP and allopregnanolone levels induced by EV in the hippocampus, hypothalamus, and pituitary but not in the adrenal glands and serum. CONCLUSIONS: In ovariectomized rats, EM-652 has an estrogen-like action that becomes antiestrogenic in the presence of EV administration. In fertile animals, EM-652 exerts estrogen-like or slight antiestrogenic effects

3d micro-structured collagen conduits for nerve repair

Introduction. Peripheral nerve injury leads to sensation and movement loss that is devastating to the patient. In cases of complete nerve transection (neurotmesis), it is often necessary to use an autologous nerve graft to bridge the injury site. Various attempts have been made to develop artificial conduits that can replace autologous grafts, but such conduits are usually only effective at bridging short gaps. Here, we have developed and tested a new form of nerve repair conduit, based on 3D microstructured collagen. Methods. Two forms of conduit were fabricated using different thicknesses of plastic compressed collagen sheet. Low density (LD) guidance-surface conduits were made from spiralling a single standard thickness (100ìm) collagen sheet. High density (HD) conduits were made from spiralling three thin collagen sheets. The HD conduits have 3x as many layers (and guidance interface) as the LD conduits. For assessment in vivo, a segment of the rat sciatic nerve was removed and a HD or LD conduit (0.5 cm in length) was implanted. Separate control experiments involved either direct repair of a sciatic nerve injury by coaptation, or insertion of an autologous graft. At 2 weeks, the implanted conduit and attached proximal and distal nerve portions were removed, fixed in formaldehyde and processed for immunocytochemistry. Results. Transverse and longitudinal sections revealed immunoreactive axons within the conduits, with axons confined to the interfaces between the spiralled collagen sheets. In the same regions an extensive cellular infiltration was present, which included numerous Schwann cells. Conclusions. The results indicate that interfaces between spiral layers of plastic compressed collagen can act as guidance and support structures for Schwann cell migration and axon regeneration. Ongoing studies are analysing the differences between the HD and LD conduits, and the topographical cues that maximise axon growth

Long-term low-dose dehydroepiandrosterone oral supplementation in early and late postmenopausal women modulates endocrine parameters and synthesis of neuroactive steroids

Abstract OBJECTIVE: To evaluate the effects of a low-dose DHEA supplementation on hormonal parameters in early and late postmenopausal women. DESIGN: Prospective case study. SETTING: Postmenopausal women in a clinical research environment. PATIENT(S): Twenty postmenopausal women were divided in two groups according to age (50-55 and 60-65 years). INTERVENTION(S): All patients underwent hormonal evaluation before and at 3, 6, 9, and 12 months of therapy (25 mg/d of DHEA orally). Pelvic ultrasound examination and Kupperman score were performed before and after 3, 6, and 12 months of therapy. MAIN OUTCOME MEASURE(S): Plasma DHEA, DHEAS, estrone (E1), E2, P, androstenedione (A), T, dihydrotestosterone, 17alpha-hydroxyprogesterone (17-OHP), cortisol (F), allopregnanolone, beta-endorphin, sexual hormone-binding globulin (SHBG), LH, FSH, growth hormone (GH), and insulin-like growth factor-1 (IGF-1) concentrations. RESULT(S): The levels of all the steroids that derive from DHEA metabolism increased in plasma with DHEA administration. Also neurosteroids (namely allopregnanolone) and endorphin showed increased plasma levels, whereas both gonadotropins were significantly reduced. Endometrial thickness did not change throughout the study period. CONCLUSION(S): Administration of low doses (25 mg) of DHEA positively modulates several endocrine parameters in early and late postmenopausal women, inducing the increase of the androgenic, estrogenic, and progestogenic milieu and reducing the climateric symptoms, similarly to estroprogestin replacement therapy. These data suggest that DHEA supplementation is a more eff

Laparoscopic management of a cornual pregnancy following failed methotrexate treatment: case report and review of literature

To describe a rare case of a singleton 8-week cornual pregnancy (CP), treated by laparoscopic incision of the uterine wall, the ectopic pregnancy was removed and the uterine site was sutured with interrupted sutures. A 21-year-old woman was admitted for suspected singleton CP at week 8. Clinical examination, b-hCG increase, and transvaginal ultrasonography (TU) were used to monitor the suspected diagnosis of an ectopic pregnancy. Following failure of methotrexate administration, surgeons performed a laparoscopy. The CP removal was performed by laparoscopic incision, enucleating the corneal mass and suturing the uterine site of the ectopic pregnancy with interrupted sutures. Intraoperative and postoperative complications and uterine integrity preservation were studied. Postoperative recovery period was normal, without intraprocedural or postprocedural complications.Uterine integrity was preserved. No further therapeutic interventions were needed in follow-up. This study confirmed the feasibility, safety and efficacy of performing a safe, minimally invasive, laparoscopic treatment of an early unruptured CP, without intraoperative and postoperative complications, with a normal postoperative recovery period and preservation of uterine integrity