Selahattin Kumru

Ghrelin is present in human colostrum, transitional and mature milk.

Ghrelin and its mRNA have recently been found in numerous human tissues including breast. The aim of this study was to compare the ghrelin levels in colostrum, mature and transitional milk and plasma in lactating women with plasma samples from non-lactating women. Venous blood samples were obtained from 17 healthy lactating women aged 22-35 years and from 16 age-matched controls. Colostrum, transitional and mature milk samples were collected just before suckling. The level of bioactive ghrelin was determined by RIA. Comparison of ghrelin values for lactating women showed significantly lower concentrations in colostrum (70.3 +/- 18 pg/ml), transitional milk (83.8 +/- 18pg/ml) and mature milk (97.3 +/- 13 pg/ml) than in the corresponding plasma samples (first day 95 +/- 16 pg/ml, 10th day 111 +/- 13 pg/ml and 15th day 135 +/- 16 pg/ml). The plasma concentrations were lower in the lactating than in the non-lactating women. Thus, the ghrelin levels in colostrum, transitional and mature milk were elavated concomitantly with increasing plasma ghrelin after delivery. The origin of milk ghrelin is not known, but it probably comes from the plasma.

COMPARISON OF SERUM COPPER, ZINC, CALCIUM, AND MAGNESIUM LEVELS IN PREECLAMPTIC AND HEALTHY PREGNANT WOMEN

Deficient or excessive levels of blood trace elements can be an adverse factor in human and animal pregnancy. The aim of this study was to investigate possible differences in the levels of serum magnesium, calcium, copper, and zinc in preeclamptic and healthy pregnant women. Samples were collected from 30 preeclamptic (PE) and 30 healthy pregnant (HP) women. The serum copper concentration was significantly lower in the PE group by 68% (p<0.0001) when compared to the healthy controls. The serum zinc and calcium were 43% and 10% lower in the PE women, respectively (both with p<0.0001), whereas the magnesium concentration showed nonsignificant differences between the two groups. Measurement of these elements may be useful for the early diagnosis of a preeclamptic condition.

Treatment of symptomatic uterine leiomyoma with letrozole

Uterine leiomyomas are the most common benign tumours of the female genital tract, often necessitating hysterectomy. The most common symptoms are dysmenorrhoea, menorrhagia, infertility and abortion. Ovarian hormones seem to play an essential role in pathogenesis, and deprivation of ovarian oestrogen causes leiomyomas to shrink significantly. The purpose of this study was to evaluate the effects of the non-steroidal aromatase inhibitor letrozole on uterine leiomyomas and on bone metabolism. A prospective, open clinical trial was conducted in a university-based hospital. Sixteen premenopausal women with symptomatic uterine leiomyomas were treated with letrozole 5 mg/day orally for 3 months. The main outcome measures of uterine and uterine leiomyoma sizes, serum FSH, LH, oestradiol concentrations, ovarian volumes and myoma-related symptoms were noted at baselines and once a month during treatment. Lumbar spine bone mineral density and biochemical markers of bone metabolism were studied at the beginning and at the end of 3 months. Letrozole significantly decreased uterine leiomyoma sizes (P < 0.01) and promptly benefited women with heavy menstrual bleeding associated with leiomyomas without changing bone mineral density. Aromatase inhibitors may represent a new generation of medications for the treatment of leiomyoma and associated symptoms. Larger clinical trials are needed, however, to fully evaluate their safety and efficacy.

Effects of raloxifene, hormone therapy, and soy isoflavone on serum high-sensitive C-reactive protein in postmenopausal women

Objective: To compare the effects of raloxifene, estradiol valerate plus dienogest, and soy isoflavones (genistein) on serum concentrations of high‐sensitive C‐reactive protein in healthy postmenopausal women. Methods: The 80 healthy postmenopausal women enrolled in the study were randomly allocated to receive 60 mg of raloxifene, 2 mg of estradiol valerate plus dienogest, 40 mg of genistein, or placebo (n = 20 in each group). Blood samples were collected at the start of the study and at 3 and 6 months. Lipid profile was also determined. Results: Only the group receiving estradiol valerate plus dienogest showed an increase in serum levels of high‐sensitive C‐reactive protein compared with baseline values and values in the control and other groups. All 3 treatments resulted in an increase in high‐density lipoprotein cholesterol levels and a decrease in total, low‐density, and very‐low‐density lipoprotein cholesterol levels. Conclusions: Estradiol valerate plus dienogest, but not raloxifene and genistein, increase serum high‐sensitive C‐reactive protein levels. All 3 treatments, however, have an estrogen‐like effect on serum lipid profile.

Serum leptin and ghrelin concentrations of maternal serum, arterial and venous cord blood in healthy and preeclamptic pregnant women

Preeclampsia, a common complication of pregnancy, is associated with alteration in the concentration of leptin in maternal blood. The action of leptin is antagonistic to that of ghrelin. Here, we compared the levels of leptin and ghrelin in maternal serum and in arterial and venous cord blood between healthy pregnant women and those suffering from mild and severe preeclampsia. The levels of leptin in maternal and newborn’s blood were elevated in both mild and severe preeclamptic patients (p<0.05). Moreover, serum ghrelin levels were negatively correlated with blood pressure and leptin/ghrelin ratio was decreased in preeclampsia (p<0.05). We concluded that increased production of ghrelin may represent a compensatory hypotensive mechanism in preeclamptic women.ResumenLa preclampsia, una complicación del embarazo, se asocia a alteración de la concentración de leptina en la sangre materna. La acción de la leptina es antagonista de la de la ghrelina. En el presente trabajo, se comparan los niveles de ambas hormonas en suero materno y en sangre arterial y venosa del cordón umbilical en embarazadas normales y en las que sufren preeclampsia leve y severa. Los resultados muestran elevación significativa del nivel de leptina en la sangre materna y fetal en caso de preclampsia, leve y severa. Además, los niveles sérios de ghrelina están negativamente correlacionados con la presión arterial y la relación leptina/ghrelina disminuye significativamente en caso de preclampsia. Es posible que la producción incrementada de ghrelina represente un mecanismo compensatorio hipotensor en mujeres con preeclampsia.

Effects of surgical menopause and estrogen replacement therapy on serum paraoxonase activity and plasma malondialdehyde concentration.

Background: We have investigated the effects of surgical menopause and estrogen replacement therapy (ERT) on serum paraoxonase 1 (PON1) activity and plasma malondialdehyde (MDA) levels in surgically postmenopausal women. Methods: Thirty-six healthy perimenopausal women who underwent total abdominal hysterectomy and bilateral salpingo-oopherectomy for uterine myoma were enrolled in this study. Blood samples were taken from the subjects 1 day before surgery, 1 day before starting ERT (30 days after the operation) and on the 30th day after the start of therapy. Results: After surgical menopause, there were significant increases in plasma MDA levels (p < 0.05) and a decrease in serum PON1 activity (p < 0.05). ERT significantly increased the PON1 activity (p < 0.05) and reduced MDA levels (p < 0.05). There was a positive correlation between serum high-density lipoprotein cholesterol and PON1 activity (r = 0.7, p < 0.001, n = 36) and a negative correlation between serum PON1 activity and plasma MDA levels (r = –0.63, p < 0.006, n = 36). Conclusions: The present study suggests that postmenopausal women tend to have high levels of plasma MDA and reduced PON1 activity, and ERT reverses these effects. The effect of ERT on lipid peroxidation seems to be associated with serum PON1 activity.

Mu opioid modulation of oxytocin secretion in late pregnant and parturient rats: Involvement of noradrenergic neurotransmission

We have investigated effects of µ- and ĸ-opioid agonists and antagonists on plasma oxytocin levels and noradrenaline content in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of 20-day pregnant rats. β-Endorphin, oxytocin, estrogen and progesterone profiles in late pregnant and parturient rats were also sought. Stage of estrous cycle was monitored by vaginal smear, and pro-estrous animals were left overnight with male. In the first set of experiments, pregnant rats were monitored and decapitated on days 20 and 21 and after the delivery of second pup. In the second set, 20-day pregnant rats were intracerebroventricularly infused with morphine (50 µg/10 µl), U50,488H (ĸ-agonist; 50 µg/10 µl), clocinnamox (µ-antagonist; 50 µg/10 µl) and norbinaltorphimine (ĸ-antagonist; 50 µg/10 µl). Controls received saline alone. Serum estrogen and progesterone levels were measured by enzyme immunoassay, and plasma oxytocin and β-endorphin by radioimmunoassay. Noradrenaline and its metabolite (3,4-dihydroxyphenylglycol) were determined in micropunched hypothalamic nuclei by HPLC-ECD. In parturient rats, oxytocin levels were increased (p < 0.05) and β-endorphin decreased (p < 0.01) compared to 20-day pregnant animals. Serum progesterone concentrations progressively declined towards parturition (p < 0.001). Clocinnamox raised oxytocin levels (p < 0.01) while U50,488H caused decreases (p < 0.05). Noradrenaline content was elevated by clocinnamox in the SON (p < 0.01) and PVN (p < 0.05) compared to control values. Other agonists and antagonists had no significant effect on the noradrenergic neurotransmission or oxytocin secretion. We suggest that noradrenaline may mediate the inhibitory effects of µ-opioids on oxytocin release. Our findings have also shown that ĸ-opioid receptors are not involved in modulation of oxytocin neurons in late pregnant rats.

Effects of aromatase inhibitors letrozole and anastrazole on bone metabolism and steroid hormone levels in intact female rats

Aim. The present study was designed to investigate the effects of two aromatase inhibitors on steroid hormone levels, bone mineral density (BMD) and bone turnover markers in intact female rats. Methods. Letrozole and anastrazole at two different dose levels were investigated for their effect on serum levels of estradiol, androstenedione, testosterone, dehydroepiandrosterone and dehydroepiandrosterone sulfate, BMD of femur and dorsal spine, and osteocalcin and pyridinoline levels as bone turnover markers. Fifty intact female rats were randomly divided in five groups (group 1 (n = 10): control, 2 ml saline; group 2 (n = 10): letrozole 1 mg/kg; group 3 (n = 10): letrozole 2 mg/kg; group 4 (n = 10): anastrazole 0.1 mg/kg; group 5 (n = 10): anastrazole 0.2 mg/kg), and oral gavages were applied for a period of 16 weeks. Results. Both doses of letrozole and anastrazole did not change femoral and vertebral BMD. Serum estradiol levels were reduced significantly at all dose levels by both agents (p < 0.001); all androgen levels were significantly elevated by letrozole (p < 0.05), although anastrazole increased only androstenedione (p < 0.05). The higher dose of letrozole increased osteocalcin levels (p < 0.05), while pyridinoline levels were increased (p < 0.05) by the higher dose of anastrazole. Conclusion. Our results indicate that short-term use of letrozole and anastrazole had no clear effects on BMD in intact rats. Further investigations are needed to understand their effects on bone metabolism in intact females.

Evaluation of mean platelet volume, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in advanced stage endometriosis with endometrioma.

OBJECTIVE We compared the preoperative values of mean platelet volume (MPV) and peripheral systemic inflammatory response (SIR) markers (neutrophil/lymphocyte ratio and platelet/lymphocyte ratio) between patients with advanced-stage (stage 3/4) endometriosis having endometrioma (OMA) and patients with a non-neoplastic adnexal mass other than endometrioma (non-OMA). MATERIAL AND METHODS Patients who underwent operations with the pre-diagnosis of infertility or adnexal mass and who underwent laparoscopic tubal ligation were included. RESULTS Haemoglobin levels, leucocyte count, platelet count, neutrophil count and lymphocyte count were not significantly different between patients with advanced stage endometriosis having OMA, patients with non-OMA and patients in the control group (p=0.970, p=0.902, p=0.373, p=0.501 and p=0.463, respectively). Patients with stage 3/4 endometriosis having OMA, patients with non-OMA and control patients were also not significantly different in terms of MPV (p=0.836), neutrophil/lymphocyte ratio (NLR) (p=0.555) and platelet/lymphocyte ratio (PLR) (p=0.358). Preoperative cancer antigen 125 (Ca-125) levels were significantly higher in patients with OMA (p=0.006). Mean size of the OMAs was significantly lower than non-OMAs (p=0.000). CONCLUSION It is very important to determine advanced stage endometriosis and OMAs during preoperative evaluation in order to inform patients and plan an appropriate surgical approach. We demonstrate that MPV, NLR and PLR values are not useful for this purpose in patients with advanced stage endometriosis that are proven to develop severe inflammation at either the cellular or molecular level.

Concentrations of preptin, salusins and hepcidins in plasma and milk of lactating women with or without gestational diabetes mellitus

This study was undertaken to ascertain whether human milk contains preptin, salusin-alpha (salusin-α) and -beta (salusin-β) and pro-hepcidin and hepcidin-25, and whether there are relationships between plasma and milk preptin, salusin-α and -β and pro-hepcidin and hepcidin-25 concentrations in lactating mothers with and without gestational diabetes mellitus (GDM). Blood was obtained from non-lactating women (n = 12), non-diabetic lactating women (n = 12), and GDM lactating women (n = 12). Colostrum, transitional milk, and mature milk samples were collected just before suckling from healthy and GDM lactating women. Peptides concentrations were determined by ELISA and EIA. Mammary gland tissues were screened immunohistochemically for these peptides. Women with GDM had significantly higher plasma and colostum preptin concentrations than healthy lactating women during the colostral and transitional milk period. Salusin-alpha and -beta levels in milk and plasma were lower in women with GDM. Salusin-α and -β were significantly lower in both plasma and colostrums of GDM than of healthy lactating women. Women with GDM had significantly higher colostum prohepcidin and hepcidin-25 concentrations than healthy lactating women during the colostral period. Plasma prohepcidin was also higher in women with GDM than in healthy lactating women during the colostral period, but plasma prohepcidin and hepcidin-25 levels decreased during mature milk period. Transitional milk pro-hepcidin and hepcidin-25 levels in women with GDM were higher than in healthy lactating women. All these results revealed that the mammary gland produces those peptides, which were present in milk at levels correlating with plasma concentrations.