From Myo-inositol to D-chiro-inositol molecular pathways.

OBJECTIVE: Inositol is a carbocyclic sugar polyalcohol. By epimerization of its hydroxyl groups, nine possible stereoisomers can be generated, two of major physiological and clinical relevance: myo-inositol and D-chiro-inositol. Myo-inositol and D-chiro-inositol are normally stored in kidney, brain and liver and are necessary for functions, such as signal transduction, metabolic flux, insulin signaling, regulation of ion-channel permeability, stress response and embryo development. In this narrative review, we summarize the mechanisms by which myo-inositol and D-chiro-inositol can be synthesized and absorbed and their possible role in the etiopathogenesis of neural tube defects. MATERIALS AND METHODS: We performed an online search in the PubMed database using the following keywords: "inositol", "D-chiro-inositol", "myo-inositol", "neural tube defects and inositol". RESULTS: Inositol requirements are partly met by dietary intake, while the rest is synthesized endogenously. Inositol deficiency may be involved in the pathogenesis of diseases, such as metabolic syndrome, spina bifida (a neural tube defect), polycystic ovary syndrome and diabetes. Supplementation of the two inositol stereoisomers, D-chiro-inositol and myo-inositol is important to prevent these conditions. CONCLUSIONS: Inositol is fundamental for signal transduction in the brain, kidneys, reproductive organs and other tissues in response to neurotransmitters, hormones and growth factors. Various genes are involved in inositol metabolism and associated pathways. Altered inositol concentrations are observed in several diseases. Analysis of the genes involved in inositol metabolism may provide important information for the clinical management of these conditions.

Vigilance on use of drugs, herbal products, and food supplements during pregnancy: focus on fosfomycin.

PURPOSE: Urinary tract infection (UTI) is defined as a common bacterial infection that can lead to significant morbidity such as stricture, fistula, abscess formation, bacteremia, sepsis, pyelonephritis, and kidney dysfunction with a mortality rates reported of 1% in men and 3% in women because of development of pyelonephritis. UTIs are more common in women and the 33% of them require antimicrobials treatment for at least one episode by the age of 24 years. UTIs are the most common infections observed during pregnancy and up to 30% of mothers with not treated asymptomatic bacteriuria may develop acute pyelonephritis which consequently can be associated to adverse maternal and fetal outcomes. All bacteriuria in pregnancy should be treated with antimicrobial treatments being safe for both the mother and the fetus. Approximately one every four women receives prescription of antibiotic treatment during pregnancy, nearly 80% of all the prescription medications during gestation. The use of fosfomycin to treat cystitis in pregnancy generally considered safe and effective. Even though use on antibiotics for urinary tract infections is considered generally safe for the fetus and mothers, this opinion is not based on specific studies monitoring the relationship of among urinary infections, consumption of antibiotics, and pregnancy outcomes. MATERIALS AND METHODS: On this basis we decided to analyze data from the database of our multicenter study PHYTOVIGGEST, reporting data from 5362 pregnancies, focusing on use of fosfomycin. Principal outcomes of pregnancy in women treated with fosfomycin were taken into consideration. RESULTS: Women who have been treated with urinary antibiotics during the pregnancy were 183. With respect to the total number of pregnancies of our sample, these women represented the percentage of 3.49% (187/5362). Analysis of different outcomes of pregnancy such as gestational age, neonatal weight, and neonatal Apgar index did not show any significant difference. At the same time, analysis of data of pregnancy complicancies (such as urgent cesarean delivery, use of general anesthesia, need to induce labor) did not show any difference in women taking fosfomycin during pregnancy and those not taking it. CONCLUSIONS: Our data, based on a large number of pregnancies, confirm the safety use of fosfomycin use in pregnancy.

Clinical and metabolic outcomes in pregnant women at risk for gestational diabetes mellitus supplemented with myo-inositol: a secondary analysis from 3 RCTs.

BACKGROUND: Gestational diabetes mellitus is defined as carbohydrate intolerance that begins or is first recognized during pregnancy. Insulin sensitizing substances such as myo-inositol have been considered for the prevention of gestational diabetes mellitus and related complications. OBJECTIVE: Because previous studies failed to show a clear reduction of gestational diabetes mellitus complications, the aim of this study was to evaluate clinical and metabolic outcomes in women who are at risk for gestational diabetes mellitus supplemented with myo-inositol since the first trimester. STUDY DESIGN: A secondary analysis of databases from 3 randomized, controlled trials (595 women enrolled) in which women who were at risk for gestational diabetes mellitus (a parent with type 2 diabetes mellitus, obese, or overweight) were supplemented with myo-inositol (4 g/d) throughout pregnancy. Main measures were the rate of adverse clinical outcomes: macrosomia (birthweight, ≥4000 g), large-for-gestational-age babies (fetal growth, ≥90 percentile), fetal growth restriction (fetal growth, ≤3 percentile), preterm birth (delivery before week 37 since the last menstruation), gestational hypertension, and gestational diabetes mellitus. RESULTS: A significant reduction was observed for preterm birth (10/291 [3.4%] vs 23/304 [7.6%]; P=.03), macrosomia (6/291 [2.1%] vs 16/304 [5.3%]; P=.04), Large-for-gestational-age babies (14/291 [4.8%] vs 27/304 [8.9%]; P=.04) with only a trend to significance for gestational hypertension (4/291 [1.4%] vs 12/304 [3.9%]; P=.07). Gestational diabetes mellitus diagnosis was also decreased when compared with the control group (32/291 [11.0%] vs 77/304 [25.3%]; P<.001). At univariate logistic regression analysis, myo-inositol treatment reduced the risk for preterm birth (odds ratio, 0.44; 95% confidence interval, 0.20-0.93), macrosomia (odds ratio, 0.38; 95% confidence interval, 0.14-0.98), and gestational diabetes mellitus diagnosis (odds ratio, 0.36; 95% confidence interval, 0.23-0.57). CONCLUSION: Myo-inositol treatment in early pregnancy is associated with a reduction in the rate of gestational diabetes mellitus and in the risk of preterm birth and macrosomia in women who are at risk for gestational diabetes mellitus.

Herb remedies during pregnancy: a systematic review of controlled clinical trials.

OBJECTIVE: The use of herbal remedies has been documented both among various patient groups and in the general population to promote health. The aim of this systematic review is to analyze the benefits of herb use during pregnancy. METHODS: A systematic literature search covering the period from January 1990 to September 2010 was performed using various electronic databases. Randomized controlled clinical trials (RCTs) were included. Paper quality was evaluated using the Jadad scale. RESULTS: Of the 511 articles identified, 14 RCTs were eligible. Ginger was the most investigated remedy and was consistently reported to ameliorate nausea and vomiting during pregnancy better than placebo; its efficacy in doing so was noted to be equal to that of vitamin B6 and dimenhydrinate. A single trial also supported the use of Hypericum perforatum for wound healing. Cranberry, however, was not efficacious in the treatment of urinary tract infections; finally, raspberry leaf did not shorten the first stage of labor, and garlic did not prevent pre-eclampsia. CONCLUSIONS: Despite the widespread, popular use of herbal remedies during pregnancy, too few studies have been devoted to specific clinical investigations. With the exception of ginger, there is no data to support the use of any other herbal supplement during pregnancy.

Herbal supplements in pregnancy: unexpected results from a multicentre study.

STUDY QUESTION: How common is the use of herbal supplements during pregnancy and does it adversely affect the pregnancy outcome? SUMMARY ANSWER: The use of herbal products during pregnancy is very common and daily almond oil spreading is associated with preterm birth (PTB). WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Herbal drugs are often promoted as 'natural' and 'safe' and such claims attract pregnant women. More than a quarter of Italian pregnant women consume herbs every day for at least 3 months during pregnancy. We raise an alert over the habit of daily almond oil spreading since it seems to be associated with PTB. DESIGN: A multicenter retrospective cohort study performed over a 15-month period. PARTICIPANTS AND SETTING: Seven hundred women interviewed within 3 days of childbirth, in three public hospitals in northern Italy. MAIN RESULTS AND ROLE OF CHANCE: One hundred and eighty-nine women were considered 'regular users', since they consumed herbs every day, for at least 3 months. Almond oil, chamomile and fennel were the most commonly used herbs. Both length of gestation and birthweight were affected by herb consumption. Almond oil users showed more pre-term birth (29 of 189) than non-users (51 of 511). After adjusting for multiple pregnancies, smoking, advanced age and drug intake, almond oil users maintained an increased risk to give birth <37th week (odds ratio = 2.09, 95% confidence interval: 1.08-4.08). BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: The association between daily spreading of almond oil and PTB only raises a hypothesis that requires confirmation in larger trials devoted to this topic. The relatively small sample size did not allow the investigation of other adverse pregnancy outcomes in herb users. GENERALIZABILITY TO OTHER POPULATIONS: The population under investigation did not significantly differ from the general population attending the same hospitals. STUDY FUNDING/COMPETING INTEREST(S): No conflict of interest exists. The study has been supported by a public grant from the University of Modena and Reggio Emilia. TRIAL REGISTRATION NUMBER: None.

Effects of myo-inositol in women with PCOS: a systematic review of randomized controlled trials.

Polycystic ovary syndrome (PCOS) affects 5%-10% of women in reproductive age, and it is the most common cause of infertility due to ovarian dysfunction and menstrual irregularity. Several studies have reported that insulin resistance is common in PCOS women, regardless of the body mass index. The importance of insulin resistance in PCOS is also suggested by the fact that insulin-sensitizing compounds have been proposed as putative treatments to solve the hyperinsulinemia-induced dysfunction of ovarian response to endogenous gonadotropins. Rescuing the ovarian response to endogenous gonadotropins reduces hyperandrogenemia and re-establishes menstrual cyclicity and ovulation, increasing the chance of a spontaneous pregnancy. Among the insulin-sensitizing compounds, there is myo-inosiol (MYO). Previous studies have demonstrated that MYO is capable of restoring spontaneous ovarian activity, and consequently fertility, in most patients with PCOS. With the present review, we aim to provide an overview on the clinical outcomes of the MYO use as a treatment to improve ovarian function and metabolic and hormonal parameters in women with PCOS.

Acupuncture versus pharmacological approach to reduce Hyperemesis gravidarum discomfort.

AIM: Several reports have suggested the use of acupuncture as a useful treatment for hyperemesis gravidarum (HG), in particular the effects on nausea intensity was underlined. The aim of this study was to compare the efficacy of acupuncture sessions plus acupressure with a metoclopramide/vitamin B12 treatment. METHODS: In this study we randomized 88 pregnant patients suffering from HG to receive either acupuncture sessions plus acupressure (acupuncture group) or metoclopramide infusion (metoclopramide group) supplemented by vitamin B12 complex. Somatic symptoms and the ability to achieve the daily routine activity (functioning) were evaluated. Acupuncture sessions were performed at the hospital twice a week for 2 weeks according to the traditional Chinese medicine criteria. Acupression was applied for 6-8 h/day. In the metoclopramide group, patients received at hospital metoclopramide infusion (20 mg/500 mL saline for 60 min) twice a week for 2 weeks. An oral supplementation with vitamin B12 complex (30 mg/day) was also prescribed. RESULTS: Both treatments reduced vomiting episodes and then nausea intensity with a consequent improvement in the rate of food intake. The effect of acupuncture seems to be progressive, increasing at the end of treatment whereas pharmacological approach has a prompt effect in responders remaining stable thereafter. Moreover, acupuncture was significantly more effective than drugs in improving functioning. CONCLUSIONS: In our study for the first time acupuncture, applied accordingly to Chinese formula, was compared to drugs demonstrating the same effect of both treatments on HG symptoms. Interestingly, functioning was significantly improved just by acupuncture. Even if the effect of acupuncture on HG discomfort remains to be confirmed, the reports on the effect of acupuncture on psychosocial variables could represent a further advantage of acupuncture application and provide an incentive to widen the base of the research.

Polyunsaturated fatty acids and risk of preterm delivery.

Preterm delivery (PD) is characterized both by increased neonatal morbidity and mortality and by important late pathologic sequelae. From a clinical stand-point, PD may results from a medical condition where the continuation of pregnancy could bring about a marked risk for the foetus and/or for the mother, or from an adverse event where the pregnancy is going to end spontaneously before 37 weeks of gestation. In the past few years some epidemiological studies have shown that diet may interfere with complex multifactorial processes contributing to the preterm triggering of labour. The attention has been focused on polyunsaturated fatty acids (PUFA) such as alpha-linoleic acid, precursor of Omega-3 series, and linoleic acid, precursor Omega-6 series. Their importance in modulating Prostaglandin concentrations at different levels is already known. Moreover, it has been reported that in clinical situation, such as PD, the endogenous levels of PUFA are unbalanced, with a Omega-6 predominance. Experimental, observational and clinical studies suggest that dietary intake of Omega-3 fatty acids is capable of significantly prolonging the duration of gestation in the range of 4-7 days; such prolongation would possibly occur through the inhibition of prostaglandins E2 and F2 alpha. In Western population dietary intake of Omega-3 appears to be marginal, and recommended assumption could be reached only by a ten-fold increase in blue fish ingestion. The recommended intake of EPA + DHA should be 1.4 g/daily with a 1:2.5 EPA:DHA. It is therefore possible to conclude that in light of controlled clinical studies and of the actual categories of risk for preterm delivery, the dietary supplementation of Omega-3, in addition to other pharmacological measures (17alpha-hydroxyprogesterone caproate), could be implemented for the secondary and/or tertiary prophylaxis of preterm delivery.

Effects of acute L-arginine infusion on non-stress test in hypertensive pregnant women.

OBJECTIVE: The present report evaluates the effect of acute L-arginine administration on fetal heart variables by a computerized non-stress test (NST) analysis. METHODS: Fifteen pregnant women at 30-34 weeks of gestational age affected by mild to moderate gestational hypertension were enrolled in the study. The study was performed in the second and third days of hospitalization. Each woman received both active (Arg) or placebo treatment (Placebo), in a double-blind, randomized, cross-over design. Women received saline infusion for 40 min, then they were infused with either placebo (saline infusion prepared by Damor Pharmaceutics and labeled as Arg-B) or Arg (L-Arg 20 g/500 ml labeled as Arg-A). RESULTS: Multiple analysis of variance (MANOVA) indicated that both placebo and Arg infusion were unable to affect cardiac variables and fetal movements. As far as maternal blood pressure changes were concerned, MANOVA indicated that active treatment showed an acute hypotensive effect on both systolic (F=8.98, p<0.001) and diastolic values (F=15.78, p>0.001). Conversely, placebo infusion does not seems to have induced any change. Considering each time of infusion we observed that Arg treatment was able to lower systolic and diastolic blood pressure after the 40 min of infusion, with this effect persisting for 20 min. CONCLUSIONS: These data indicate that the acute, intravenous administration of high-dose L-arginine does not induce significant changes in fetal heart rate (FHR), whereas it lowers maternal blood pressure. Such conclusions are reinforced by the observation that saline administration in the same pregnant women was neutral for both FHR and maternal blood pressure values. According to previous studies, it seems conceivable that maternal L-arginine treatment enters the fetal circulation by crossing the placenta. The lack of changes in FHR, however, suggests that no significant hemodynamic changes were induced by the treatment. Contrary to what happens in the mother, this may possibly be due to a low, if any, conversion of L-arginine to nitric oxide in the fetus.

Acupuncture plus moxibustion to resolve breech presentation: a randomized controlled study.

OBJECTIVE: In many Western countries breech presentation is an indication for elective Cesarean section. In order to correct fetal presentation, the stimulation of the acupoint BL67 by moxibustion, acupuncture or both has been proposed. Since no studies had previously been carried out on Western populations, pregnant Italian women at 33-35 weeks gestational age carrying a fetus in breech presentation were enrolled in a randomized, controlled trial involving an active BL67 point stimulation and an observation group. METHODS: A total of 240 women at 33-35 weeks of gestation carrying a fetus in breech presentation were randomized to receive active treatment (acupuncture plus moxibustion) or to be assigned to the observation group. Bilateral acupuncture plus moxibustion was applied at the BL67 acupoint (Zhiyin). The primary outcome of the study was fetal presentation at delivery. RESULTS: Fourteen cases dropped out. The final analysis was thus made on 226 cases, 114 randomized to observation and 112 to acupuncture plus moxibustion. At delivery, the proportion of cephalic version was lower in the observation group (36.7%) than in the active-treatment group (53.6 %) (p = 0.01). Hence, the proportion of Cesarean sections indicated for breech presentation was significantly lower in the treatment group than in the observation group (52.3% vs. 66.7%, p = 0.03). CONCLUSIONS: Acupuncture plus moxibustion is more effective than observation in revolving fetuses in breech presentation. Such a method appears to be a valid option for women willing to experience a natural birth.

Psychoneuroendocrine correlates of secondary amenorrhea.

Functional hypothalamic amenorrhea is a common, non-organic and theoretically reversible form of anovulation due to reduced hypothalamic GnRH drive. Numerous studies suggest that this altered hypothalamic homeostasis is caused by a synergism between psychogenic challenge, promoted in part by dysfunctional attitudes, and metabolic compromise induced by undernutrition and overexercise. The recent growing interest in psychiatric comorbidity underlines the importance of reconsidering the boundaries between psychological disorders and somatic conditions. That not withstanding, it is mandatory in gynecological endocrinology to explore the issue of secondary amenorrhea from a psychoneuroendocrine perspective in order to devise biopsychosocial interventions which address the individual distress. In this brief review we will try to critically discuss the issue providing evidences from personal studies as clues for better understanding the extent of the complex psychoneuroendocrine network controlling menstrual function.

Autonomic and neuroendocrine responses to stress in patients with functional hypothalamic secondary amenorrhea.

OBJECTIVE: To evaluate the ability of women affected by functional hypothalamic secondary amenorrhea (FHSA) or polycystic ovary syndrome (PCOS) to adapt to stress. DESIGN: Controlled clinical study. SETTING: University hospital. PATIENT(S): Thirty-one patients affected by FHSA, 29 patients with PCOS, and 30 eumenorrheic women. INTERVENTION(S): The subjects took the Stroop Color Word (Stroop CW) test and underwent blood sampling. MAIN OUTCOME MEASURE(S): Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and serum cortisol levels. RESULT(S): The healthy controls had better Stroop CW scores than patients with FHSA. Serum cortisol levels significantly increased during Stroop CW with respect to the baseline in patients with FHSA or PCOS but not in the healthy controls. The SBP, DBP, and HR of the controls as well as SBP and DBP of patients with PCOS were significantly higher than those measured in patients with FHSA both at the baseline and during Stroop CW. CONCLUSION(S): Patients with FHSA do not cope as well as healthy patients, and their autonomic response to stress is worse than both controls and patients with PCOS.

Hypothalamic resetting at puberty and the sexual dimorphism of migraine.

It is well known that migraine is far more represented in females than in males. However, this gender-related difference is present only during reproductive life since in prepubertal children, migraine prevalence figures are independent of sex. Thus, transition to puberty accounts for changes which render females more susceptible to migraine attacks. In females, the main driver of the hormonal events allowing sexual maturation is the pulsatile secretion of hypothalamic LHRH modulated by opioid activity. Clinical reports suggest that migraine attacks could be prevented by the abolition of this neurohormonal secretion. On the other hand, several clinical and experimental observations have focused on neuroendocrine systems (opiatergic, serotonergic, adrenergic) as participating in the constitution of the so-called "migraine trait", the biological predisposition in patients that would explain their sensitivity to migraine triggers. Such neuroendocrine secretions are mainly dependent upon hypothalamic activity where a sexual dimorphic nucleus has been discovered in the preoptic area. We suggest that the sexual dimorphism of migraine should be sought in hypothalamic networks related to LHRH secretion.

L-arginine infusion reduces blood pressure in preeclamptic women through nitric oxide release.

OBJECTIVE: This study investigates the biochemical and cardiovascular effects of L-arginine administration in normotensive pregnant women and women with preeclampsia. METHODS: The study groups consisted of 12 women with uncomplicated pregnancies and 17 preeclamptic patients, four of whom were on antihypertensive treatment. In both groups, saline infusion was started, followed by 30 g L-arginine administration, and finally more saline. Blood pressure was recorded every 5 minutes and blood samples were collected for measurement of serum citrulline, arginine, and nitrite levels. Amino acid assays were done by using high-performance liquid chromatography with fluorometric detection. RESULTS: L-Arginine infusion was associated with a significant reduction of blood pressure in both groups, the decrease being greater in the women with preeclampsia. Baseline serum citrulline and arginine levels were not significantly different between the two groups. L-Citrulline levels were significantly increased during infusion of L-arginine, and the increase was significantly lower in the women with preeclampsia. Serum nitrite levels were increased only in controls and not in preeclampsia patients. The total citrulline production stimulated by L-arginine was related inversely to baseline blood pressure values and was unrelated to clinical parameters such as gestational age at delivery, birth weight, and Apgar score. CONCLUSIONS: L-Arginine load in pregnant women is associated with increased nitric oxide (NO) production and hypotension. Despite a reduced ability to produce NO, patients with preeclampsia may benefit from L-arginine supplementation. Overall, these findings partially support the hypothesis that preeclampsia is characterized by a dysfunction of the L-arginine-NO pathway.

Adjuvant L-arginine treatment for in-vitro fertilization in poor responder patients.

The objective of the present study was prospectively and randomly to evaluate the role of L-arginine in improving uterine and follicular Doppler flow and in improving ovarian response to gonadotrophin in poor responder women. A total of 34 patients undergoing assisted reproduction was divided in two groups according to different ovarian stimulation protocols: (i) flare-up gonadotrophin-releasing hormone analogue (GnRHa) plus elevated pure follicle stimulating hormone (pFSH) (n = 17); and (ii) flare-up GnRHa plus elevated pFSH plus oral L-arginine (n = 17). During the ovarian stimulation regimen, the patients were submitted to hormonal (oestradiol and growth hormone), ultrasonographic (follicular number and diameter, endometrial thickness) and Doppler (uterine and perifollicular arteries) evaluations. Furthermore, the plasma and follicular fluid concentrations of arginine, citrulline, nitrite/nitrate (NO2-/NO3-), and insulin-like growth factor-1 (IGF-1) were assayed. All 34 patients completed the study. In the L-arginine treated group a lower cancellation rate, an increased number of oocytes collected, and embryos transferred were observed. In the same group, increased plasma and follicular fluid concentrations of arginine, citrulline, NO2-/NO3-, and IGF-1 was observed. Significant Doppler flow improvement was obtained in the L-arginine supplemented group. Three pregnancies were registered in these patients. No pregnancies were observed in the other group. It was concluded that oral L-arginine supplementation in poor responder patients may improve ovarian response, endometrial receptivity and pregnancy rate.

L-arginine infusion decreases platelet aggregation through an intraplatelet nitric oxide release.

Nitric Oxide (NO) inhibits platelet aggregation via activation of an intraplatelet soluble guanylate cyclase which induces an increase in cyclic GMP (1). It has been also demonstrated that platelets contain a constitutive, calcium-dependent, NO synthase which is activated by collagen-induced platelet aggregation. This leads to a NO synthesis from L-Arginine (L-Arg), which in turn increases cyclic GMP and down-regulates platelet aggregation (2). In vitro administration of supraphysiological concentrations of L-Arg enhances platelet cyclic GMP levels by increasing NO production and reduces platelet aggregation. This effect is reversed by pre-incubation with NO-synthase inhibitors (3). These results indicate that the L-Arg: NO pathway plays an important role in the modulation of human platelet aggregation (4). In vivo L-Arg, when administered i.v., induces hypotension (5) and vasodilatation (6,7) in humans, and when orally supplemented reduces platelet aggregability both in hypercholesterolemic rabbits and healthy men (8,9).

Effects of a yeast-based dietary supplementation on premenstrual syndrome. A double-blind placebo-controlled study.

A dietary approach has proven to be effective in alleviating symptoms of premenstrual syndrome. In our previous studies, magnesium improved premenstrual irritability and mood scoings. In this double-blind, placebo-controlled study, we evaluated the effects of a new dietetic preparation (Sillix Donna, Giuliani) in 40 patients affected by mild to moderate premenstrual syndrome. Premenstrual symptoms were scored in both follicular and luteal phases, at baseline, at 2nd, 4th and 6th month of treatment by using the Menstrual Distress Questionnaire (MDQ). Twenty patients were randomised to receive the active preparation and 20 placebo. MDQ scores at baseline were similar in the two groups. Five patients of the placebo group dropped out because of treatment failure. No side effects were observed. Both treatments reduced symptoms already in the 2nd month, but the active preparation was more effective at all time controls (p < 0.05); at the 6th month it significantly reduced premenstrual MDQ scores to 18% of baseline values, placebo only to 73%. These data demonstrate that Sillix Donna is effective in reducing premenstrual distress.

Immunocytochemical evidence for the presence of Met-enkephalin and Leu-enkephalin in distinct neurons in the brain of the elasmobranch fish Scyliorhinus canicula.

Immunohistochemical methods have been used to investigate the distribution of various opioid peptides derived from mammalian proenkephalin in the central nervous system of Scyliorhinus canicula. The results indicate that both Leu- and Met-enkephalin-immunoreactive peptides are present in the dogfish brain. In contrast, enkephalin forms similar to Met-enkephalin-Arg-Phe or Met-enkephalin-Arg-Gly-Leu, and mammalian alpha-neo-endorphin, dynorphin A (1-8), dynorphin A (1-13), and dynorphin A (1-17) were not detected. Met- and Leu-enkephalin immunoreactivities were found in distinct neurons of the telencephalon and hypothalamus. In particular, cell bodies reacting only with the Met-enkephalin antiserum were localized in the preoptic nucleus and in the suprachiasmatic region of the hypothalamus. Conversely, cell bodies reacting only with the Leu-enkephalin antiserum were localized in the pallium and the nucleus lobi lateralis hypothalami. Several areas of the telencephalon and diencephalon exhibited both Met- and Leu-enkephalin-like immunoreactivity, but the two immunoreactive peptides were clearly contained in distinct perikarya. The overall distribution of Met-enkephalin-immunoreactive elements in the dogfish exhibited similarities to the distribution of proenkephalin-derived peptides previously reported for the brain of tetrapods. The fact that Met- and Leu-enkephalin-like peptides were detected in distinct neurons, together with the absence of dynorphin-related peptides, suggests the existence of a novel Leu-enkephalin-containing precursor in the dogfish brain.

Immune and neuroendocrine response to restraint in male and female rats.

A parallel study of the modification in the opioid and immunological systems induced by acute restraint (RT) was carried out in male and female rats 24 hr after the treatment. beta-Endorphin-like immunoreactivity (beta-ELI) was measured in two brain areas (ventral hypothalamus [HYP] and periaqueductal gray matter [PAG]) and in the pituitary (anterior and neurointermediate lobes), together with plasma corticosterone (C) and ACTH. Immune function was measured as mitogen-induced Interferon-gamma (IFN-gamma) production by splenocytes. RT reduced beta-ELI levels in the PAG in males and females. Plasma levels of C and ACTH did not differ from the basal levels in restrained animals. RT reduced IFN-gamma production in both sexes, but this effect was more marked in females than in males. The possible relationship between the immune and opioid system is discussed.

Stressful life events and affective disorders inhibit pulsatile LH secretion in hypothalamic amenorrhea.

The aim of this study was to evaluate relationships between emotional state and hypothalamic activity in patients with hypothalamic secondary amenorrhea. Sixty-seven normal weight patients with hypothalamic amenorrhea were submitted to concomitant psychological and LH pulsatility evaluation. Structured clinical interview for anxiety and depressive disorders (DSM III-R) as well as life events investigations (Paykel test) were performed. LH pulses (blood sampling every 10 min for 4 hr) were analyzed through DETECT program and Instantaneous Secretory Rate were computed. Twenty-one patients reporting life events associated to the onset of amenorrhea had LH pulse frequency (2.28 +/- 1.10 pulses/4 hr) lower than those without life events (3.40 +/- 1.46 p = .007). LH pulses amplitude was lower in patients meeting a DSM III-R (21 cases: 1.22 +/- 0.96 mIU/ml) diagnosis than in those without (1.99 +/- 1.20 p = .04) diagnosis. Plasma estradiol and FSH levels as well as duration of amenorrhea and Body Mass Index were similar among groups. It is concluded that psychogenic factors (namely the presence of life events related to the onset of menstrual disorder) are associated with significant and specific changes of hypothalamic activity which could be involved in determining hypogonadism.