Resveratrol Triggers Apoptosis Through Regulating Ceramide Metabolizing Genes in Human K562 Chronic Myeloid Leukemia Cells

Cancer is a major worldwide health problem and one of the leading causes of death either in developed or developing countries. Plant extracts and derivatives have always been used for various disease treatments and many anticancer agents issued from plants and vegetables are clinically recognized and used all over the world. Lycium europaeum (Solanaceae) also called “wolfberry” was known since ancient times in the Mediterranean area as a medicinal plant and used in several traditional remedies. The Lycium species capacity of reducing the incidence of cancer and also of halting or reserving the growth of cancer was reported by traditional healers. In this study, the antiproliferative capacity, protective properties, and antioxidant activity of the hydro-alcoholic fruit extract of Lycium europaeum were investigated. Results showed that Lycium extract exhibits the ability to reduce cancer cell viability, inhibits proliferation, and induces apoptosis in A549 human lung cancer cells and PC12 rat adrenal medulla cancer cells, in a concentration- and time-dependent manner. Cytotoxic effect on normal rat cerebellum granule cells was assessed to be nonsignificant. Results also showed that Lycium fruit extract protected lipids, proteins, and DNA against oxidative stress damages induced by H₂O₂ via scavenging reactive oxygen species.     

Prolactin-releasing action of a low dose of exogenous gonadotropin-releasing hormone throughout the human menstrual cycle

Pharmacological doses of gonadotropin-releasing hormone (GnRH) are known to induce prolactin (PRL) release in different pathological states. The same effect can be observed in postmenopausal women and during the phases of menstrual cycle characterized by high estrogen levels. With the aim to evaluate whether nonpharmacological doses of GnRH are also able to induce PRL release, gonadotropin and PRL response to a low dose of GnRH (10 micrograms, i.v. bolus) was evaluated in 70 normal women during different phases of their menstrual cycle. A significant PRL increase was observed in 33% of subjects during the first days of the cycle (menstrual phase; days 1-3 from the beginning of menstrual bleeding: n = 6), in 24% of subjects during early follicular phase (days -10 to -8 from LH peak: n = 17); in 38% of subjects during midfollicular phase (days -6 to -4 from LH peak: n = 8); in 78% of subjects during preovulatory phase (days -2 to -1 from LH peak; n = 9); in 67% of subjects during postovulatory phase (days +1 to +2 from LH peak; n = 6) and in 42% of subjects during midluteal phase (days +5 to +8 from LH peak; n = 24). In brief, the increase of mean PRL levels after GnRH administration was only significant (p less than 0.05) during pre- and postovulatory phases. The percentage of patients who showed a PRL response during the different phases of menstrual cycle was significantly correlated to the mean maximal net increase of LH (r = 0.927; p less than 0.01) and to the mean maximal net increase of FSH (r = 0.926; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women

OBJECTIVE: The effect of melatonin on human carbohydrate metabolism is not yet clear. We investigated whether melatonin influences glucose tolerance and insulin sensitivity in aged women. PATIENTS: Twenty-two postmenopausal women of whom 14 were on hormone replacement therapy. DESIGN: After an overnight fast, at 0800 hours on two nonconsecutive days, placebo or melatonin (1 mg) were administered randomly and in a double blind fashion. Forty-five minutes later, an oral glucose tolerance test (75 g; OGTT) was performed in 13 women. In another nine women insulin-dependent (Si) and -independent (Sg) glucose utilization was tested by a frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS: Areas under the response curve to OGTT (AUC) for glucose (1420 +/- 59 vs. 1250 +/- 55 mmol x min/l; P < 0.01), and C-peptide (42,0980 +/- 45,320 vs. 33,528 +/- 15,779 pmol x min/l; P < 0.02) were higher following melatonin than placebo, while Si values were lower (2.6 +/- 0.28 units vs. 3.49 +/- 0.4 units; P < 0.03). Si modifications induced by melatonin were inversely related to Si values of the placebo day (r(2) = 0.538; P < 0.025). CONCLUSIONS: The present results indicate that in aged women administration of 1 mg of melatonin reduces glucose tolerance and insulin sensitivity. The present data may have both physiological and clinical implications.     

Evidence that estrogens inhibit LH secretion through opioids in postmenopausal women using naloxone

To evaluate whether ovarian steroid environment may modify endogenous opioid activity at hypothalamic-pituitary level, the effects of naloxone infusion (1.2 mg/h for 4 h) on gonadotropin secretion were studied in 5 postmenopausal women who had natural menopause 3-5 years before the study. In addition, naloxone infusion was repeated in the same subjects after chronic oral treatment with conjugated estrogens (1.25 mg/day in two divided doses for 20 days). Before treatment, both the circulating levels of estrogens and plasma gonadotropins were in the normal range for postmenopausal women and naloxone infusion did not induce any significant modification of gonadotropin secretion. In contrast, after estrogen therapy, and the consequent rise in estrogen plasma levels, naloxone infusion induced a significant LH increase (p less than 0.01) starting during the last hour of treatment. These findings seem to confirm that endogenous opioid peptides may modulate the inhibitory effect exerted by estrogens on LH secretion, in humans.     

Repeated transient hypergonadotropic amenorrhea during pharmacologic induction of multiple follicular development with exogenous gonadotropins

Human gonadotropins are widely used for induction of ovulation in the treatment of anovulatory infertility and for induction of multiple follicular development (MFD) in in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), and artificial insemination with husband's semen (AIH) programs. Reported is a patient with normal menstrual cycles, who had two episodes of gonadal unresponsiveness to human gonadotropin therapy, followed by transient hypergonadotropic amenorrhea ("resistant ovary" syndrome), during induction of MFD in conjunction with AIH as treatment for unexplained infertility. The first episode occurred during the sixth cycle of a first series of MFD induction with daily intramuscular injections of exogenous gonadotropins. The second episode occurred during the second cycle of a second series of MFD induction with intravenous pulsatile administration of FSH. On both occasions, normalization of endogenous gonadotropin levels and reappearance of ovulatory cycles occurred spontaneously, after two and three months, respectively. A similar mechanism could occur in the failures of MFD induction observed in IVF programs.