Tryptophan catabolism to serotonin and kynurenine in women undergoing in-vitro fertilization.

This cross-sectional clinical study was designed to explore the impact of tryptophan-kynurenine and tryptophan-serotonin (5 HT) pathways on reproductive performance during in vitro fertilization (IVF). Paired serum and follicular fluid (FF) samples were obtained from 64 consecutive IVF patients. The analysis was done by using LC-MS/MS. Ovarian hyperstimulation resulted in decreased serum tryptophan (p<0.004), 5-HT (p<0.049) and kynurenine (p<0.001). FF levels of tryptophan (R=0.245, p<0.051), kynurenine (R=0.556, p<0.001) and 5-HT (R=0.523, p<0.001) were positively related to their respective serum levels. Clinical pregnancy was associated with higher serum 5-HT (p<0.045) and FF 5-HT (p<0.020) and lower kynurenine to 5-HT ratio (p<0.024). Chemical pregnancy was also positively related to FF 5-HT (R=0.362, p<0.024). Moreover, there was a direct relationship of the number of mature oocytes to the FF 5-HT (R=0.363, p<0.020) but it was inversely related to FF tryptophan to 5-HT and FF kynurenine to 5-HT ratios (R=-0.389, p<0.016 and R=-0.337, p<0.036, respectively). Multivariate logistic regression revealed that the number of mature oocytes was significantly influenced by FF 5-HT (?=0.473, p<0.001). In IVF patients ovarian hyperstimulation results in a reduction of the availability of tryptophan to catabolic pathways to kynurenine and 5-HT. Outcome measures improved significantly when 5-HT predominated over kynurenine.

The role of apoptosis in the complex pathogenesis of the most common obstetrics and gynaecology diseases.

PURPOSE: We aimed to assess the etiological role of apoptotic genes Bcl-2 and Bax in the background of major obstetric and gynaecological diseases. METHODS: Placental tissue samples were collected from 101 pregnancies with intrauterine growth restriction and 104 pregnancies with premature birth with 140 controll samples from term, eutrophic newborns. In addition, gene expression assessment of the genes Bax and Bcl-2 was performed in 101 uterine leiomyoma tissue samples at our disposal with 110 control cases. Gene expression levels were assessed by PCR method. RESULTS: The expression of the Bcl-2 gene was decreased in placental samples with intrauterine growth restriction. Significant overexpression of the proapoptotic Bax gene was detected in samples from premature infants. Antiapoptotic Bcl-2 gene expression was found to be significantly increased in fibroid tissues. CONCLUSION: Apoptosis plays a crucial role in the development of the most common OB/GYN conditions. Decrease in the placental expression of the antiapoptotic gene Bcl-2 may upset the balance of programmed cell death.

Special aspects of social support: Qualitative analysis of oncologic rehabilitation through a belly dancing peer support group.

Tumour-related peer support groups (PSGs) show long-term development in quality of life and coping, and decrease distress in cancer care. To clarify channels of social support in oncologic rehabilitation by combined exercise and psychosocial therapy, individual semi-structured interviews were conducted after 1 year additional belly dance rehabilitation in a closed PSG among 51 patients with malignant tumour diagnosis in Budapest, Hungary. Interview data were transcribed and analysed using qualitative content analysis (ATLAS.ti 6 Win). Results suggest that group experience provides emotional-, practical- and informational support. We could point out specific social effects of "role model" function and extend the coping model. The group dispose all the features of effective suggestion and may be effectively applied as additional therapy for patients with malignancies. The extended coping model and the introduction of "role model" function could be useful for PSGs' efficacy assessment.

Endometrioid adenocarcinoma arising from adenomyosis: a case report.

BACKGROUND: Endometriosis is most commonly found in the peritoneum of the lesser pelvis and in the genital tract (in the ovaries). Its malignant transformation is quite rare, which usually appears in patients who previously underwent surgical procedures aimed at treating endometriosis. Years of hormone substitution (unopposed estrogen therapy) is also considered to have a role. According to the present authors' current knowledge, these are mostly well-differentiated tumors with low malignancy, which are primarily treated surgically. CASE: In the present case the authors present a 73-year-old female patient who underwent a laparotomy due to abdominal pain and a mass in the lesser pelvis. The authors performed hysterectomy along with bilateral adnexectomy and omental resection. The histological examination of the specimens verified an endometrial adenocarcinoma formed on the ground of adenomyosis and the endometrial adenocarcinoma of the left ovary. CONCLUSION: The malignant transformation of endometriosis is rare, and the mechanisms how it develops on the grounds of adenomyosis is currently unclear.

Wintertime surgery increases the risk of conversion to hip arthroplasty after internal fixation of femoral neck fracture.

UNLABELLED: The study demonstrates that wintertime surgeries are associated with impaired fracture healing and increases the risk of conversion to hip arthroplasty after osteosynthesis of femoral neck fracture. Furthermore, the results raise the possibility of association between seasonal changes in vitamin D levels and impaired fracture healing of femoral neck fracture. INTRODUCTION: Although the changes of vitamin D level and calcitropic hormones influencing bone metabolism are seasonal, the effect of seasons on hip fracture healing is unknown. We assessed the effects of seasonal periodicity on conversion to hip arthroplasty after primary osteosynthesis of femoral neck fracture. METHODS: This nationwide retrospective observational cohort study involved 2779 patients aged ≥ 60 years who underwent internal screw fixation for primary femoral neck fracture and were discharged in 2000. Cases requiring conversion to arthroplasty during the 8-year follow-up derived from the Hungarian health insurance database were registered. Risk factors assessed included sex, age, fracture type, season of primary surgery and surgical delay. Competing-risks regression analysis was used for data analyses. RESULTS: During the observation period, 190 conversions to hip arthroplasty (6.8%) were identified, yielding an overall incidence of 19.5 per 1000 person-years. The crude incidence rates of conversions after osteosynthesis in winter, spring, summer and fall were 28.6, 17.8, 16.9 and 14.7 per 1000 person-years, respectively. Besides younger age, female sex and intracapsular fracture displacement, wintertime primary osteosynthesis significantly increased the risk of conversion (fall vs. winter, hazard ratio (HR): 0.50, 95% confidence interval [95% CI 0.33-0.76]; spring vs. winter, HR: 0.63, [95% CI 0.44-0.92]; summer vs. winter, HR: 0.62, [95% CI 0.42-0.91]). CONCLUSIONS: Our study demonstrate that wintertime primary osteosynthesis increases the risk of conversion surgeries. The results may help improving the outcome of primary fixation of femoral neck fractures.

Comparative study of PEP mask and Flutter on expectoration in cystic fibrosis patients.

The objective of the study was to investigate the effect of positive expiratory pressure (PEP) and Flutter on expectoration in cystic fibrosis (CF) patients. Data was gathered through 260 treatments with 10 patients (5 female; 19.2 years; BMI: 18.0). Two methods were used alternately, first the patients started with Flutter and proceeded with PEP, and the next occasion they exercised in the reverse order, starting with PEP then continuing with Flutter. During each phase, 5 sets of 10 exhalations were performed. Sputum weight was measured after the use of the first device, and at the end of the treatment. During sessions starting with Flutter 4.0 ± 4.0 g sputum was expectorated, continuing with PEP, an additional 5.2 ± 5.0 g was produced, altogether 9.2 ± 8.2 g. At sessions starting with PEP 7.4 ± 3.7 g was expectorated, continuing with Flutter an additional 0.8 ± 1.4 g, that is 8.2 ± 4.1 g. Comparing the two devices by themselves, PEP proved to be significantly more efficient then Flutter. Comparing the two treatment types it is statistically not proven, which one is preferable using both devices. Conclusively, PEP is significantly more efficient than the Flutter in sputum expectoration among CF patients. The Flutter is a useful supplementary device.

Effects of pituitary adenylate cyclase activating polypeptide on human sperm motility.

Pituitary adenylate cyclase activating polypeptide (PACAP), a neuropeptide with diverse effects, was originally isolated as a hypothalamo-hypophyseal peptide. Subsequent studies showed highest levels of PACAP in the testis after the brain, suggesting that it influences the development and functioning of spermatozoa. Indeed, it has been proven that PACAP has an effect on spermatogenesis, both locally and via influencing the hypothalamo-hypophyseal-gonadal axis. The aim of the present study was to determine whether PACAP has an effect on human sperm motility and whether it is present in the human seminal fluid. Furthermore, the sperm head morphology was studied in mice lacking endogenous PACAP. Human samples were obtained from healthy adult volunteers and andrological patients. The effects of PACAP on the motility of human sperm cells were investigated using a computer aided sperm analysis system. In cases where the motility was lower, addition of PACAP to the samples increased the motility and the ratio of rapid progressive and medium progressive sperm motility groups. The presence of PACAP could not be detected in human seminal fluid samples by means of mass spectrometry. Investigating sperm head morphology with routine histology in PACAP deficient mice revealed that both the longitudinal and transverse diameters were significantly lower in PACAP deficient mice, without marked difference in the shape, as revealed by scanning electron microscopy.

Correlation between oocyte number and follicular fluid concentration of pituitary adenylate cyclase-activating polypeptide (PACAP) in women after superovulation treatment.

Follicular growth, ovulation, and luteinization are influenced by interactions of peptide and steroid hormone-signaling cascades in the ovary. Pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in the regulation of several endocrine processes and is present in ovarian follicular fluid (FF). However, little is known about PACAP in FF with regard to maturation, ovulation, fertilization, and successful pregnancy. The aim of this pilot study was to investigate whether there is a correlation between PACAP concentration in FF and ovarian response to superovulation treatment in infertile women, performed in volunteers (n = 132; aged between 20 and 35). After treatment, the number of harvested oocytes was recorded and PACAP immunoreactivity in FF was measured by radioimmunoassay. All the corresponding PACAP concentrations were below 290 fmol/ml in cases when the number of harvested oocytes exceeded 14 per patient, while in all cases above 290 fmol/ml, the number of oocytes was below 14. Using these cutoff values, we determined three study groups: high-PACAP concentration, high-oocyte number, and low-PACAP concentration-low-oocyte number groups. Median values of PACAP concentration in these groups were 411.2, 106.5, and 101.0 fmol/ml, respectively, while the median values of harvested oocytes were 5.5, 19.0, and 5.0, respectively. Differences were significant, indicating a correlation between concentration of PACAP in FF and the number of recruited oocytes. Higher concentrations of PACAP in FF might be associated with lower number of developing oocytes, while low concentrations of PACAP might correlate with a markedly higher number of ova retrieved, thus predicting a higher chance for ovarian hyperstimulation. Our present study is among the first few human clinical studies with direct conclusions drawn for possible clinical impact of PACAP.

Investigation of pituitary adenylate cyclase activating polypeptide in human gynecological and other biological fluids by using MALDI TOF mass spectrometry.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional and pleiotropic neuropeptide. PACAP has diverse effects in the endocrine system, among others, it plays important roles in oogenesis, implantation and development of the nervous system. However, it is not known whether PACAP is present in the fluids of the human reproductive organs. The aim of the present study was to determine, by means of mass spectrometry and radioimmunoassay, whether PACAP is present in human amniotic fluid, ovarian follicular fluid and cervico-vaginal fluid. Samples were obtained from healthy adult volunteers. Our MALDI TOF and MALDI TOF/TOF spectrometry results show that PACAP38 is present in all of the follicular fluid samples, and PACAP-like immunoreactivity was also measured by radioimmunoassay. However, we did not find the characteristic peak representing the unmodified 38 amino acid form of the peptide in normal cervico-vaginal smear and amniotic fluid samples. Furthermore, we analyzed other body fluids for comparison, such as human nasal fluid, saliva and aqueous humor. PACAP was not found in these latter samples. In summary, the present study provides evidence for the presence of PACAP in human follicular fluid, suggesting a role in oocyte function, but determination of the exact physiological significance awaits further investigation.

Negative association of L-arginine methylation products with oocyte numbers.

BACKGROUND: The aim of this study was to determine the concentrations of L-arginine and methylarginines in follicular fluid obtained from women participating in our IVF program and to find clinical correlates of these biochemical parameters. METHODS: Follicular fluid was obtained from 108 women by ultrasonography guided transvaginal puncture following controlled ovarian hyperstimulation. Follicular fluid L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and monomethylarginine (MMA) concentrations were determined with liquid chromatography-tandem mass spectrometry. The integrated index of arginine methylation (arg-MI) was calculated according to the formula: arg-MI = (ADMA + SDMA)/MMA. RESULTS: There were significant inverse relationships between IVF embryo number and follicular fluid L-arginine (r = -0.507, P < 0.001), ADMA (r = -0.356, P < 0.024), SDMA (r = -0.347, P < 0.028), MMA (r = -0.449, P < 0.004) and to L-arginine/ADMA ratio (r = -0.328, P < 0.031). By contrast, arg-MI was directly related to IVF embryo number (r = 0.426, P < 0.006). Moreover, the number of IVF oocytes was also inversely related to ADMA (r = -0.202, P < 0.037) and MMA (r = -0.384, P < 0.012) and positively to arg-MI (r = 0.450, P < 0.03). CONCLUSIONS: The elevated levels of follicular fluid l-arginine and methylarginines appear to have an adverse influence on the reproductive processes as reflected by a reduction in the number of oocytes and embryos conceived. In contrast, the integrated methylation index proved to be positively correlated to the above parameters of fertilization.

Alterations of pituitary adenylate cyclase-activating polypeptide-like immunoreactivity in the human plasma during pregnancy and after birth.

BACKGROUND: Since its discovery, several distinct effects of pituitary adenylate cyclase activating polypeptide (PACAP) have been established - predominantly in animal studies - in the nervous system, various peripheral organs as well as in the endocrine regulation. It is unknown whether PACAP has any effect on human pregnancy regarding either utero-maternal or perinatal aspects of the gestation. AIM: We investigated alterations of PACAP38-like immunoreactivity (PACAP38-LI) in the human plasma throughout normal pregnancy, during and after delivery, and its level in the umbilical vessels, as well as in the peripheral blood of term healthy newborns. MATERIALS AND METHODS: A 2 ml blood sample was used for each test, PACAP38-LI was determined by radioimmunoassay. RESULTS: In the 2nd and 3rd trimester significant elevation was observed in the PACAP38-LI compared to the earlier gestation and non-pregnant conditions. During delivery its level significantly decreased and returned to the original values 3 days after birth. In the neonates PACAP38-LI level of the peripheral blood was similar to that of healthy adults, but umbilical arteries and veins contained significantly lower concentrations of PACAP38-LI. Besides, the levels were lower in the umbilical vein compared to the artery. CONCLUSIONS: PACAP38-LI levels show sensitive change during normal pregnancy and delivery. Our findings suggest that the fetal organs actively synthesize PACAP. Further investigations are required to elucidate the physiological importance of the alterations observed.

Pelvic pain in endometriosis: painkillers or sport to alleviate symptoms?

To assess potential individual factors influencing quality of life and pain scores of patients suffering from histologically confirmed endometriosis. Study using a questionnaire among patients of reproductive age undergoing laparoscopy with a presumed diagnosis of endometriosis. Details of fertility, previous treatments and quality of life, sexual activity, as well as linear pain scores for several symptoms, were recorded. Details of intraoperative findings were also collected and only those data were used where endometriosis was intraoperatively and histologically proven. A questionnaire before surgery gathered information from women on the following groups of variables: age, marital status, education, reproductive and medical history including previous pregnancies and parity, knowledge of accompanying pelvic disorders, regular sport activity, as well as general quality of life estimates including self-image. Pelvic pain was scored using a visual analogue scale. Data were statistically evaluated. Eighty-one patients complaining about persistent pelvic pain were later intraoperatively and histologically proven to have endometriosis. Thirty-one of them (38.2%) reported regular sport as part of their daily life schedule while 50 of them (61.8%) performed no physical activity at all. Fourteen patients among regular exercisers and 33 patients among those without physical activity reported the effectiveness of painkillers for pelvic pain, corresponding to 45.1% and 66% of these subgroups, respectively (difference statistically significant, p<0.05). Based on our results, we can conclude, that taking painkillers might be less effective among endometriosis patients performing regular daily sport activities, and, thus it might impose them to an unnecessary burden of possible side-effects.

Organic hydroperoxide-induced chemiluminescence of follicular fluid and blood serum samples obtained from women pretreated for in vitro fertilization.

The organic hydroperoxide-induced chemiluminescence of follicular fluid obtained from in vitro fertilized patients and its differently separated fractions were evaluated. Peroxidative stress causes a different photo-emission in the samples which alludes to some factors playing a role in the maintenance of the pro-oxidant/antioxidant balance. Interactions between the protein compounds of the samples and the organic hydroperoxide associate with formation of excited species contributing to the distinctive light emission processes. The technique offers a special re-interpretation of the scavenger state relating to the components of follicular fluid.

Issues to debate on the Women's Health Initiative: estrogen: an instrument or the conductor of the orchestra?

Although it is well known that cyclic production of sex hormones is essential to establish reproductive function and female characteristics, distant impacts of the activity of the female endocrine system result from a concert of delicate mechanisms. Estrogen is rather an instrument than a conductor in this physiological orchestra of the female. Thus, controversies in the explanation of results from studies on hormone replacement therapy (HRT) and cardiovascular disease (CVD) prevention might be eliminated, if we analyse not only the role of estrogen but a broader spectrum of factors leading to CVD. Authors would like to hypothesize that haemorheological changes in women around menopause, such as increased blood and plasma viscosity, haematocrit and fibrinogen, are largely responsible for the increased mortality in the post-menopausal life period. We believe that a cyclic withdrawal bleeding establishes a more favourable haemorheological condition, thus, sequentially administered estrogen might be protective in post-menopausal women. Nevertheless, other factors, that decrease blood viscosity, such as daily exercise, intake of ample amount of fluids as well as ideal nutrition, are equally important. We are confident that sequential HRT, as well as healthy life style and risk prevention programmes have their proper place in the management of this issue.

The effect of catecholamines, acetylcholine and histamine on progesterone release by human granulosa cells in a granulosa cell superfusion system.

There are experimental data demonstrating the presence and actions of various neurotransmitters in the ovary, thus supporting the view that they might play a role in intraovarian regulatory mechanisms, although their exact function in the regulation of ovarian hormone secretion is unclear. The objective of the present study was to investigate the direct action of catecholamines, acetylcholine and histamine on progesterone secretion of human granulosa cells in a superfused cell system. Human granulosa cells were isolated from preovulatory follicular fluid using a Percoll gradient centrifugation method. Approximately 2 x 10(6) cells were mixed with Sephadex G-10 and were transferred into two chambers of the superfusion apparatus. The system was perfused with a culture medium and test materials were added to the system at a dose of 100 pmol/ml. The progesterone concentration of samples was measured using an (125)I radioimmunoassay. Administration of epinephrine (adrenaline), norepinephrine (noradrenaline), dopamine and histamine had no effect on progesterone release. However, acetylcholine produced a significant progesterone release, which could be blocked by atropine. The observed effect of acetylcholine on progesterone release of superfused human granulosa cells may reflect a physiological role of acetylcholine in the regulation of granulosa cell function during the menstrual cycle.