Lethal and sub-lethal responses of the biogenic reef forming polychaete Sabellaria alveolata to aqueous chlorine and temperature.

Sabellaria alveolata, a reef-forming marine polychaete, was exposed to aqueous chlorine which is routinely used as an anti-fouling agent in power station cooling water. Worms were treated to a range of chlorination levels (0, 0.02, 0.1 and 0.5 mg l(-1) Total Residual Oxidant referred to as control, low, intermediate and high TRO) at mean and maximum summer temperatures (18 and 23 °C respectively). Overall mortality was relatively low, however a combination of high temperature and intermediate and high TRO resulted in a significant increase in mortality compared to the control and low TRO treatments. In contrast the extension of dwelling tubes was reduced at high TRO, but increased at low and intermediate TRO levels relative to the controls independent of temperature. Finally, tube strength was found to decrease with increasing TRO, again independent of temperature. On the basis of these findings, S. alveolata can be considered tolerant of one month exposures to low TRO at water temperatures up to and including the summer maxima for southern UK waters. However, at higher TRO levels and during warm weather, high mortality would be predicted.

The impact of depression and fluoxetine treatment on obstetrical outcome.

INTRODUCTION: This study prospectively followed women over the course of pregnancy to assess the impact of depression and/or antidepressant treatment on obstetrical outcome. METHOD: Sixty-four outpatient women with an Axis I diagnosis of major depressive disorder or no psychiatric history were followed in each trimester of pregnancy with administration of the CES-D. A subset of the women with depression received treatment with fluoxetine during pregnancy. Subjects with a CES-D score greater than 16 at any time point were further assessed for the presence of an active major or minor depressive episode. Primary outcome variables included infant gestational age, birth weight, Apgar score, and admission to the neonatal intensive care unit. RESULTS: Analyzable data were available for 62 women. No significant differences were found in outcome variables between those women with exposure to medication and/or prenatal depressed mood and those women without a history of depression. CONCLUSIONS: In contrast to other studies, our study did not demonstrate an adverse effect of fluoxetine exposure per se on obstetrical outcome. In addition, we did not find a significant impact of depression during pregnancy on obstetrical outcome.

Fluoxetine and norfluoxetine concentrations in nursing infants and breast milk.

BACKGROUND: This study's goal was to characterize nursing infants' exposure to fluoxetine through breast milk and to identify variables for minimizing such exposure. METHODS: Nursing women on stable daily doses of fluoxetine were recruited into the study. Breast milk, maternal and infant serum concentrations of fluoxetine and norfluoxetine were determined with high-performance liquid chromatography. RESULTS: Nineteen nursing women one with a pair of dizygotic twins participated in the study. The women were on stable daily doses of fluoxetine (10-60 mg/day) and all but two took the medication during the last trimester of pregnancy. Fluoxetine was detectable in 30% (n = 6) of the nursing infant sera (< 1-84 ng/mL), whereas norfluoxetine was found in 85% (N = 17) (< 1-265 ng/mL). Peak breast milk concentrations occurred approximately 8 hours after maternal dosing and predicted norfluoxetine concentrations in infant serum. Maternal serum fluoxetine and norfluoxetine concentrations correlated highly with infant norfluoxetine concentrations. A daily maternal fluoxetine dosage of 20 mg or lower was significantly less likely to produce detectable concentrations of either fluoxetine or norfluoxetine in infants compared to higher daily dosages. No adverse effects were reported in any infant. CONCLUSIONS: Our findings demonstrate that maternal serum and peak breast milk concentrations of fluoxetine and norfluoxetine predict nursing infant serum norfluoxetine concentrations. In nursing women taking 20 mg/day or less of fluoxetine, infant serum concentrations were typically low.

Use of sertraline, paroxetine and fluvoxamine by nursing women.

BACKGROUND: The pharmacological treatment of depression in nursing women requires information on the magnitude of medication exposure to the infant that may occur through breast milk. AIMS: To examine serum concentrations of antidepressants in infants exposed to these medications through breast-feeding. METHOD: Maternal and infant serum concentrations of sertraline, paroxetine and fluvoxamine were determined with high-performance liquid chromatography (limit of detection=1 ng/ml). RESULTS: No detectable medication was present in any infant exposed to paroxetine (n=16) or fluvoxamine (n=4). Among infants exposed to sertraline (n=30), detectable medication was present in 24% of serum samples. A significant negative correlation was found between infant age and infant serum concentration. Sertraline was significantly more likely to be detected in an infant if the mother's daily dose was 100 mg or higher. No adverse sequelae occurred in any infant. CONCLUSIONS: This study shows that paroxetine, fluvoxamine and sertraline produce minimal exposure to infants when taken by nursing mothers.

The use of psychotropic medications during breast-feeding.

OBJECTIVE: The authors reviewed the risks and benefits regarding the use of psychiatric medications during breast-feeding as they relate to the health and well-being of mothers and their infants. Strategies are discussed to limit infant exposure to a medication while effectively treating the nursing mother. METHOD: A MEDLINE search of the literature since 1955 was conducted to determine the use of psychotropic medications in breast-feeding women. Search items included each of the categories of psychopharmacologic agents as well as each of the agents in association with nursing, breast-feeding, postpartum, lactation, and breast milk. RESULTS: No controlled studies on the safety of psychotropic medications in nursing mothers were found. Case reports and small case series for each of the different psychotropic medications serve as the basis for suggested treatment guidelines for the management of psychiatric illnesses in breast-feeding women. Thus, each case needs to be considered on an individual basis, with a thoughtful analysis of the risks and benefits of nursing and exposure of the infant to medication. The baseline clinical status of the infant should also be reviewed. CONCLUSIONS: Women are vulnerable postpartum to psychiatric disorders and frequently face the need to decide whether to take psychotropic medications while breast-feeding. Should psychiatric medication be indicated, the parents should be provided with the available information regarding the effects of these medications on the neonate. In this way, an informed decision can be made. When psychotropic medication is used during breast-feeding, it is strongly recommended that the infant's pediatrician be involved in monitoring the infant.

Detection and quantification of ATP and heavy metal with electronical micro-circuits.

In order to use whole eukaryotic cells as an active element in the detection and amplification of biological signals, for both in vitro and in vivo applications, we have undertaken a first approach to interface live cells and integrated circuit, and evaluate the possibility to develop a microbioreactor. An amplified photodiode system was designed and built as an electronical circuit in a way that it could easily be miniaturised. In parallel micro-chips with silicium chambers were used as microbioreactors to adhere cells. We showed here that this etched silicon chamber allows endothelial and CHO cells spreading, permitting determination of a number of cell properties {\it on line} providing appropriate integrated circuits are designed to perform the desired functions. The photodiode system reacting to the luminescent luciferase system permitted, through the use of appropriate software from a personal computer (PC) connected on line in vitro, the determination of ATP concentration, and using different luciferase transfected bacteria permitted the detection of constitutive or induced luminescence.

A general artificial neural network for the modelization of culture kinetics of different CHO strains.

Animal cell cultures are characterized by very complex nonlinear behaviors, difficult to simulate by analytical modeling. Artificial Neural Networks, while being black box models, possess learning and generalizing capacities that could lead to better results. We first trained a three-layer perceptron to simulate the kinetics of five important parameters (biomass, lactate, glucose, glutamine and ammonia concentrations) for a series of CHO K1(Chinese Hamster Ovary, type K1) batch cultures. We then tried to use the same trained model to simulate the behavior of recombinant CHO TF70R. This was achieved, but necessitated to synchronize the time-scales of the two cell lines to compensate for their different specific growth rates.

Adhesion, growth and detachment of cells on modified polystyrene surface.

By adsorbing poly(N-isopropylacrylamide) (PNIPAAm) from an aqueous solution onto oxidised polystyrene without the need for grafting the polymer to the surface, we showed here that cells(CHO-K1) adhere and grow well at 37 degrees C and are detached by lowering the temperature to 10 degrees C without any other deleterious treatment. Both bacterial culture grade polystyrene Petri dishes and polystyrene beads (120 to 250mum diameters) commercially available used in static conditions of growth were tested with similar results. The contact angle of modified Petri dishes with a water droplet increases from 36 to 58 degrees when the temperature is raised from 25 to 37 degrees C indicating change in hydrophilicity of the surface as a function of temperature.

Increased productivity of recombinant tissular plasminogen activator (t-PA) by butyrate and shift of temperature: a cell cycle phases analysis.

Directed control of cell metabolism by a modification of the physicochemical conditions (presence of Na-butyrate and modification of the temperature) was used to modulate the productivity of human recombinant tissular plasminogen activator (t-PA) expressed under control of SV40 promoter in Chinese Hamster Ovary (CHO) cell lines. We showed that both by adding Na-butyrate or lowering temperature from 37 degrees C to 32 degrees C there is an increase in the amount of t-PA excreted, while cell growth is significantly reduced. The treatments also increased the intracellular amount of t-PA. We measured the distribution of cell cycle phases by cytometry and used a modification of the equations of Kromenaker and Srienc (1991, 1994 a, b) to analyse the intracellular t-PA production rate in the different cell cycle phases. Intracellular t-PA was shown to accumulate in G1 phase in all conditions (at 37 degrees C, at 32 degrees C and in presence of butyrate). Moreover, we have shown that the distribution of the time cells treated by butyrate are maintained in the G1cell cycle phase is significantly increased. t-PA produced in the different cell culture conditions tested was analysed by zymogram and western blotting: neither butyrate, neither the shift of temperature changed significantly the overall quality of the protein. The N-glycan patterns of recombinant human t-PA was also analysed with carbohydrate-specific lectins. Butyrate caused a transitory increase in N-linked complex high-mannose oligosaccharides without any effect on the sialic acid content of t-PA.

Gender and bipolar illness.

BACKGROUND: For major depression and schizophrenia, gender differences have been reported in symptom expression and course of illness. Gender differences in bipolar disorder are becoming increasingly apparent, but have been less studied. Research data on these differences will help determine whether gender is important in influencing illness variables such as course, symptom expression, and likelihood of comorbidity. METHOD: Charts of 131 patients (63 women and 68 men) with a DSM-IV diagnosis of bipolar disorder admitted to the University of California Los Angeles Mood Disorders Program over a 3-year period were reviewed to gather data on demographic variables and course of illness and to assess differences in the illness across genders. RESULTS: No significant gender differences were found in the rate of bipolar I or bipolar II diagnoses, although women were overrepresented in the latter category. Also, no significant gender differences emerged in age at onset, number of depressive or manic episodes, and number of hospitalizations for depression. Women, however, had been hospitalized significantly more often than men for mania. Further, whereas bipolar men were significantly more likely than bipolar women to have a comorbid substance use disorder, women with bipolar disorder had 4 times the rate of alcohol use disorders and 7 times the rate of other substance use disorders than reported in women from community-derived samples. CONCLUSION: For bipolar disorder, course of illness variables such as age at onset and number of affective episodes of each polarity do not seem to differ across genders. Women, however, may be more likely than men to be hospitalized for manic episodes. While both men and women with the illness have high rates of comorbidity with alcohol and other substance use disorders, women with bipolar disorder are at a particularly high risk for comorbidity with these conditions.

Medication status and polycystic ovary syndrome in women with bipolar disorder: a preliminary report.

BACKGROUND: In patients with epilepsy, polycystic ovary (PCO) syndrome has been reported to be associated with the use of the anticonvulsant divalproex sodium. Whether PCO syndrome is associated with divalproex use in patients with bipolar disorder has not previously been explored. METHOD: Twenty-two female outpatients with a DSM-IV diagnosis of bipolar disorder who were between the ages of 18 and 45 years (inclusive) and who were taking lithium and/or divalproex (10, divalproex monotherapy; 10, lithium monotherapy; 2, divalproex/lithium combination therapy) were evaluated. Patients completed questionnaires about their medical, psychiatric, and reproductive health histories, and body mass indices were calculated. In the early follicular phase of their menstrual cycle, women were examined for hirsutism, given a pelvic ultrasound, and/or assessed for changes in laboratory values such as serum levels of testosterone, free testosterone, estradiol, estrone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, luteinizing hormone, follicle-stimulating hormone, and 17-OH progesterone. RESULTS: All 10 patients on lithium monotherapy, 6 of 10 patients on divalproex monotherapy, and both of the patients on divalproex/lithium combination therapy reported some type of menstrual dysfunction, which, in 4 cases, had preceded the diagnosis of bipolar disorder. Hirsutism was not common in any group, but obesity was prominent in all groups. Ovarian ultrasound revealed an increased number of ovarian follicles in 1 patient taking lithium and in none of the patients taking divalproex. Hormonal screening did not indicate PCO-like changes in any patient. CONCLUSION: In this pilot study of bipolar patients, PCO-like changes were not seen in women receiving divalproex or lithium. However, independent of therapeutic agent used, the bipolar women in this study reported high rates of menstrual disturbances, suggesting that the hypothalamic-pituitary-gonadal axis may be compromised in some women with bipolar disorder.

Postpartum and nonpostpartum depression: differences in presentation and response to pharmacologic treatment.

Following childbirth, major depression (postpartum depression) affects approximately 8-12% of new mothers. However, little is known about the pharmacological management of postpartum depression, and no studies to date have assessed differences in treatment response between women with postpartum and nonpostpartum major depression. The authors reviewed the records of 26 women with postpartum major depression and 25 women with major depression unrelated to childbearing (nonpostpartum depression) who presented to them for treatment over a 4-year period. Compared with the nonpostpartum depressed patients, the postpartum depressed women were significantly more likely to present with anxious features. Also, cases of postpartum depression were more severe than cases of nonpostpartum depression. While the postpartum patients were equally as likely to recover (as defined by a Clinical Global Impression score of 1 or 2) compared to the nonpostpartum-depressed patients, their time to response was significantly longer. By 3 weeks of pharmacotherapy, 75% of the nonpostpartum cases had recovered, in contrast to only 36% of the postpartum cases. Further, postpartum patients were significantly more likely to be receiving more than one antidepressant agent at the time of response to treatment. Length of depression prior to treatment did not explain the difference in treatment response. Presence of depressive symptoms during pregnancy and timing of onset of the depression (before vs. after 4 weeks of delivery) did not affect likelihood of treatment response in this sample. Women with postpartum depression appear to be significantly more likely than the nonpostpartum women to present with anxious features, take longer to respond to pharmacotherapy for depression, and require more antidepressant agents at the time of response to treatment.

Antidepressant medications, mood and male fertility.

By modulating the activity of central neurotransmitters, psychotropic agents may affect reproductive functioning in men and women. Many neurotransmitters influence the hypothalamic-pituitary-gonadal (HPG) axis and can consequently affect menstrual cycling in women and spermatogenesis in men. Emotional state similarly may disrupt reproductive functioning through the effects of stress hormones on the HPG axis. While some data exist on the relationship between stress and menstrual cyclicity in women of reproductive age, little is known regarding the potential effect of emotional state on reproductive function in men. This paper will review: (1) aspects of male reproductive function that may be vulnerable to medication-induced influences; (2) the impact of emotional state on male reproductive function; and (3) the literature on the possible effects of antidepressant medications on male fertility.

Lithium-induced subclinical hypothyroidism: review of the literature and guidelines for treatment.

BACKGROUND: This review addresses the definition, prevalence, etiology, and clinical significance of lithium-associated subclinical hypothyroidism and offers guidelines for evaluation and treatment of this condition. DATA SOURCES: MEDLINE was used to search all articles written in English from 1964-present that included the words lithium and thyroid; lithium and subclinical hypothyroidism; mood and thyroid function; and bipolar illness and thyroid function. STUDY FINDINGS: Lithium interferes with thyroid metabolism and increases the incidence of overt and subclinical hypothyroidism. Subclinical hypothyroidism may be associated with the presence of somatic and neuropsychiatric symptoms and interfere with treatment responsiveness. CONCLUSION: A careful assessment of thyroid function is recommended prior to initiating lithium treatment and during maintenance treatment. Recommendations regarding the threshold for initiation of thyroxine supplementation in patients with lithium-associated subclinical hypothyroidism are discussed in relationship to the degree of detrimental effects potentially associated with thyroid dysfunction.

Age-dependent inaccuracy of asthma death certification in Northern England, 1991-1992.

Asthma mortality appeared to increase two-fold in the UK from the mid- 1970s to the early 1990s, but there is evidence of inaccuracy in asthma death certification and so a region-wide investigation was undertaken to assess whether this recorded statistical trend might have been partly or wholly artefactual. A total of 35 respiratory physicians, distributed in panels of three, systemically reviewed the hospital and general practice records of 210 subjects with physician-diagnosed asthma who died in 1991 and 1992. The death certificates indicated that asthma was considered to be the primary cause of death in 103 (group 1), a contributory cause in 70 (group 2) and not relevant in 37 (group 3). There was agreement within the panels that 43% of the subjects had probably never suffered from asthma. Discordance between the panels and the certifying physicians over the correct death certification category was high for group 1 (45% for those aged <65 yrs, 75% for those aged > or =65 yrs and 64% overall) and group 2 (67%), but much less for group 3 (22%). This study concludes that asthma death certification provides a markedly inaccurate picture of asthma mortality, particularly in elderly subjects. Thus, it is speculated that if the magnitude of this source of inaccuracy has increased over the last two decades, the apparent recent increase in asthma mortality may be largely artefactual.

Evaluation of mental health and depression during pregnancy: position paper.

Women in their reproductive years constitute the population at greatest risk for major depression. Consequently, many women will experience depression during the course of conception and pregnancy. Rates of major depression among pregnant women appear to be equivalent to those of nongravid women. The evaluation of depression during pregnancy, however, is confounded by the somatic experiences normative at this time. A small number of rating instruments have been validated among pregnant women and should take precedence in research studies until new instruments are developed specifically for this group. Other issues that require further exploration are risk factors for depression during pregnancy and the course of depression during pregnancy.