[Diagnostic and therapeutic algorithm for the treatment of premenstrual dysphoric disorder]. / Dijagnosticke i terapijske smjernice za lijecenje predmenstruacijskog disforicnog poremecaja.

Many women experience psychological and physical symptoms associated with menstrual cycle. In 3% to 5% of women that meet the criteria for premenstrual dysphoric disorder, the symptoms are severe and impair their social and occupational functioning. Although the etiology of premenstrual dysphoric disorder is unknown, the symptoms of dysphoria, including depression and anxiety, have been associated with serotonergic dysregulation. Selective serotonin reuptake inhibitors, taken only during the symptomatic luteal phase, are considered as first-line therapy for premenstrual dysphoric disorder.

Nitric oxide synthesis in placenta is increased in intrauterine growth restriction and fetal hypoxia.

In order to study the possible role of nitric oxide (NO) in the human placenta, we measured the concentration of its stable metabolite nitrite (NO2-) in the placentas of women with normal pregnancies and those from pregnancies complicated by intrauterine growth restriction (IUGR) with or without fetal hypoxia. We have measured nitrites by the Griess reaction in 15 placentas from IUGR pregnancies and 12 controls. Cerebroumbilical ratio (C:U) was recorded by color Doppler ultrasound and values below 1 were considered to be a predictor for fetal hypoxia. NO2- levels measured in pathological placentas were increased for at least 93% as compared to control. Subjects from pregnancies complicated by IUGR and fetal hypoxia had increased NO2- as compared to the placentas from pregnancies with IUGR and normal fetal oxygenation. NO production in placenta is increased in pregnancies with IUGR. This effect is more pronounced in those with compromised fetal oxygenation.

Fetal cerebrovascular response to chronic hypoxia--implications for the prevention of brain damage.

Fetal hypoxia is one of the leading causes of perinatal morbidity and mortality. One of the most severe sequels of fetal hypoxic insult is the development of perinatal brain lesions resulting in a spectrum of neurological disabilities, from minor cerebral disorders to cerebral palsy. One of the most important fetal adaptive responses to hypoxia is redistribution of blood flow towards the fetal brain, known as the 'brain sparing effect'. The fetal blood flow redistribution in favor of the fetal brain can be detected and quantified by the Doppler cerebral/umbilical ratio (C/U ratio = cerebral resistance index (CRI)/umbilical resistance index (URI)). Our studies on animal models and human fetuses have demonstrated clearly that this phenomenon cannot prevent the development of perinatal brain lesions in the case of severe or prolonged hypoxia. Fetal deterioration in chronic and severe hypoxia is characterized by the disappearance of the physiological cerebral vascular variability (vasoconstriction and vasodilatation), followed by an increase in cerebral vascular resistance. However, our latest study on growth-restricted and hypoxic human fetuses has shown that perinatal brain lesions can develop even before the loss of cerebrovascular variability. The fetal exposure to hypoxia can be quantified by using a new vascular score, the hypoxia index. This parameter, which takes into account the degree as well as duration of fetal hypoxia, can be calculated by summing the daily % C/U ratio reduction from the cut-off value 1 over the period of observation. According to our results, the use of this parameter, which calculates the cumulative, relative oxygen deficit, could allow for the first time the sensitive and reliable prediction and even prevention of adverse neurological outcome in pregnancies complicated by fetal hypoxia.

[Nitric oxide--an important signalling molecule in normal and pathological pregnancy]. / Dusikov oksid--vazna signalna molekula u normalnoj i patoloskoj trudnoci.

The numerous studies on the multifunctional nature of the nitric oxide (NO) have suggested the wide variety of functions mediated by this molecule in vital processes in cardiovascular, nervous, gastrointestinal, urogenital system and during immunological reactions. In this review we present the results of experiments carried out on animal models, as well as the results of clinical studies considering the role of NO and its metabolites during pregnancy and delivery. During pregnancy NO is one of the most important relaxing factors of myometrium, and also no less important in the control of blood flow in uterus and placenta. Changes in NO production at the end of pregnancy could be important for the beginning of delivery and cervical maturation. Also it seems, and our preliminary results as well as results of other investigators suggest, that higher levels of NO are produced during some pathological conditions in pregnant women, e.g. IUGR, preeclampsia, preterm delivery. The implications of NO donors or inhibitors of NO synthesis used in therapy of previously mentioned conditions will be also discussed.