Inger Johanne Bakken

Gender differences in subjective well-being, self-esteem and psychosocial functioning in adolescents with symptoms of anxiety and depression: findings from the Nord-Trøndelag Health Study

Gender differences in the prevalence of symptoms of anxiety and depression during adolescence are well documented. However, little attention has been given to differences in subjective well-being, self-esteem and psychosocial functioning between boys and girls with symptoms of anxiety and depression. The aim of this study was to investigate gender differences in the associations between such symptoms and subjective well-being, self-esteem, school functioning and social relations in adolescents. Data were taken from a major population-based Norwegian study, the Nord-Trøndelag Health study (HUNT), in which 8984 (91% of all invited) adolescents, aged 13-19 years, completed an extensive self-report questionnaire. Although prevalence rates of symptoms of anxiety and depression were higher in girls than in boys, a significant interaction between gender and symptoms of anxiety and depression was found in respect of each of the following outcome variables: subjective well-being, self-esteem, academic problems, frequency of meeting friends and the feeling of not having enough friends. These interactions indicate that the associations between symptoms of anxiety and depression and lower subjective well-being and self-esteem, more academic problems in school and lower social functioning were stronger for boys than for girls. Our findings may contribute to an earlier assessment and more efficient treatment of male adolescent anxiety and depression.

Metabolism of lactate in cultured GABAergic neurons studied by 13C nuclear magnetic resonance spectroscopy

Primary cultures of mouse cerebral cortical neurons (GABAergic) were incubated for 4 hours in media without glucose containing 1.0 mmol/L [U-13C]lactate in the absence or presence of 0.5 mmol/L glutamine. Redissolved, lyophilized cell extracts were analyzed by 13C nuclear magnetic resonance spectroscopy to investigate neuronal metabolism of lactate and by HPLC for determination of the total amounts of glutamate (Glu), γ-aminobutyric acid (GABA), and aspartate (Asp). The 13C nuclear magnetic resonance spectra of cell extracts exhibited multiplets for Glu, GABA, and Asp, indicating pronounced recycling of labeled tricarboxylic acid cycle constituents. There was extensive incorporation of 13C label into amino acids in neurons incubated without glutamine, with the percent enrichments being approximately 60% for Glu and Asp, and 27% for GABA. When 0.5 mmol/L glutamine was added to the incubation medium, the enrichments for Asp, Glu, and GABA were 25%, 35%, and 25%, respectively. This strongly suggests that glutamine is readily converted to Glu and Asp but that conversion to GABA may be complex. The observation that enrichment in GABA was identical in the absence and presence of glutamine whereas cycling was decreased in the presence of glutamine indicates that only C-2 units derived from glutamine are used for GABA synthesis, that is, that metabolism through the tricarboxylic acid cycle is a prerequisite for GABA synthesis from glutamine. The current study gives further support to the hypothesis that cellular metabolism is compartmentalized and that lactate is an important fuel for neurons in terms of energy metabolism and extensively labels amino acids synthesized from tricarboxylic acid cycle intermediates (Asp and Glu) as well as the neurotransmitter in these neurons (GABA).

[U-13C]glutamate metabolism in astrocytes during hypoglycemia and hypoxia

The ability of cultured astrocytes to metabolize [U‐13C]glutamate in the absence of glucose was investigated by utilizing 13C nuclear magnetic resonance spectroscopy to identify 13C‐labeled metabolites. Control cultures (3 mM glucose), hypoglycemic cultures (glucose‐deprived), severe hypoglycemic cultures (glucose‐deprived, 0.5 mM iodoacetate as an inhibitor of glycolysis), hypoglycemic/hypoxic cultures, and cultures deprived of all additional substrates were incubated for 2 hr in medium containing 0.5 mM glutamate (50% [U‐13C]glutamate). Glucose deprivation alone had little effect on removal of glutamate from the culture medium, but the presence of iodoacetate or incubating cultures in a low‐oxygen atmosphere decreased glutamate clearance. Only the withdrawal of all substrates other than glutamate decreased glutamine synthesis. Metabolism of glutamate through the tricarboxylic acid (TCA) cycle was evident by the appearance of [1,2,3‐13C]glutamate and [U‐13C]aspartate in cell extracts and [U‐13C]lactate in cell media. Lactate derived from TCA cycle intermediates was significantly reduced after glucose deprivation and even more so after severe hypoglycemia. Release of glutamate from astrocytes was observed under all incubation conditions. [U‐13C]Aspartate was not detected in control media but was released from glucose‐deprived cells when oxygen was available. Increased release was observed in the presence of iodoacetate. After withdrawal of all substrates other than glutamate, [U‐13C]aspartate was the only metabolite observed intracellularly, whereas aspartate, glutamine, and 5‐oxoproline were detected in the incubation medium. The present results indicate that glutamate‐to‐aspartate conversion is preferentially utilized by astrocytes when oxygen is available but glycolysis is impaired. J. Neurosci. Res. 51:636–645, 1998.

Lactate formation from [U-13C]aspartate in cultured astrocytes: compartmentation of pyruvate metabolism.

Metabolism of [U-13C]aspartate in cultured astrocytes and the effects of inhibitors of malic enzyme and phosphoenolpyruvate carboxykinase (hydroxymalonate and 3-mercaptopicolinic acid, respectively) were studied using 13C nuclear magnetic resonance (NMR) spectroscopy. The labelling of glutamate and glutamine showed entry of aspartate into the tricarboxylic acid (TCA) cycle after conversion to oxaloacetate. Production of [U-13C]pyruvate from [U-13C]aspartate was revealed by the presence of [U-13C]lactate in incubation media. Furthermore, labelling patterns in C-2 and C-3 in intracellular aspartate showed entry of [1,2-13C]acetyl-CoA into the TCA cycle; evidence for pyruvate-recycling. No reduction in [U-13C]lactate was observed in the presence of either enzyme inhibitor. However, 3-mercaptopicolinic acid reduced incorporation of labelled acetyl-CoA into TCA cycle intermediates, indicating compartmentation of pyruvate production in astrocytes.

[U‐13C]aspartate metabolism in cultured cortical astrocytes and cerebellar granule neurons studied by NMR spectroscopy

The metabolism of [U‐13C]aspartate was studied in cultured cortical astrocytes and cerebellar granule neurons in the presence of glucose and during inhibition of glycolysis. Redissolved, lyophilized cell extracts and incubation media were analyzed by 13C nuclear magnetic resonance spectroscopy for the determination of metabolites labeled from aspartate. Uniformly labeled lactate was prominent in control media of astrocytes and cerebellar granule neurons. In both cell types, aspartate entered the tricarboxylic acid (TCA) cycle, as shown by labeling patterns in glutamate and, in astrocytes, in glutamine. From the complex labeling patterns in aspartate in astrocytic perchloric acid extracts it was clear that acetylcoenzyme A (acetyl‐CoA) derived from aspartate via oxaloacetate and pyruvate could enter the TCA cycle. Such “recycling,” however, could not be detected in cerebellar granule neurons. Inhibition of glycolysis reduced aspartate uptake and metabolism in both cell types. Most notably, lactate derived from aspartate showed a large reduction, and in astrocytes, incorporation of labeled acetyl‐CoA into the TCA cycle was significantly reduced. Thus, astrocytes and cerebellar granule neurons differ in their handling of aspartate. Furthermore, inhibition of glycolysis clearly affected aspartate metabolism by such cells. GLIA 23:271–277, 1998.

Incidence of pelvic inflammatory disease in a large cohort of women tested for Chlamydia trachomatis: a historical follow-up study

BackgroundChlamydia trachomatis is a highly prevalent sexually transmitted disease. Testing rates among young Norwegian women are high. Young women diagnosed with C. trachomatis are often worried about future complications.MethodsOur cohort consisted of 24,947 women born 1970–1984 who were tested for C. trachomatis infection during 1990–2005. We linked C. trachomatis laboratory data to data on hospitalizations for pelvic inflammatory disease during 1990–2005. Cox regression analysis with time-dependent covariates adjusted for age at first test was used to assess the association between C. trachomatis history and pelvic inflammatory disease.ResultsFollow-up until the end of 2005 included 201,387 woman-years. The incidence rate of hospitalization for pelvic inflammatory disease was higher among women with prior C. trachomatis infection than among women with negative tests only (48 events during 32,057 person-years and 143 events during 169,192 person-years, corresponding to 0.15 and 0.08 per 100 person-years, respectively). The corresponding hazard ratio adjusted for age at first test was 1.69 (95% CI, 1.21–2.36).ConclusionOur data show a link between a diagnosis of C. trachomatis infection and subsequent pelvic inflammatory disease. However, pelvic inflammatory disease was a rare event irrespective of C. trachomatis status. These, together with other recent findings, can be used to reassure women worried about their future reproductive health following a diagnosis of C. trachomatis.

NMR spectroscopy study of the effect of 3‐nitropropionic acid on glutamate metabolism in cultured astrocytes

3‐Nitropropionic acid (3‐NPA) is a selective and irreversible inhibitor of succinate dehydrogenase. The effect of this compound on the metabolism of [U‐13C]glutamate was studied in astrocytes using 13C nuclear magnetic resonance spectroscopy. The appearance of [1,2,3‐13C]glutamate in cell extracts and [1,2,3‐13C]glutamine and [U‐13C]lactate in cell media demonstrated the metabolism of labeled glutamate via the tricarboxylic acid cycle. Such labeling was observed in the control situation and also in cells treated with 3 mM 3‐NPA. In the cells treated with 3 mM 3‐NPA, however, the labeling was significantly reduced, and with 10 mM 3‐NPA no such labeling was observed. Labeled aspartate was observed in untreated cells only. Labeled succinate was not detectable under control conditions, but increased dose dependently in the presence of 3‐NPA. Glutamate uptake and conversion of [U‐13C]glutamate to U‐13C]glutamine was largely unaffected by 3‐NPA, and ATP content was unchanged. In a previous study using cerebellar neurons, tricarboxylic acid cycle metabolism was blocked with 3 mM 3‐NPA. The present results show that astrocyte metabolism is more adaptable to blockade of the tricarboxylic acid cycle by 3‐NPA than neuronal metabolism. J. Neurosci. Res. 47:650–654, 1997.

Vasodilation in porcine ophthalmic artery : peptide interaction with acetylcholine and endothelial dependence

Co-activation of cranial perivascular sensory and parasympathetic fibres in vivo induces simultaneous release of several vasodilatory substances with neurotransmitter or neuromodulatory roles. The role of the endothelium and possible interactions between such substances are poorly understood. The objective of this study was therefore to investigate these aspects with the sensory dilator calcitonin gene-related peptide (CGRP) and the parasympathetic dilators acetylcholine (ACh) and vasoactive intestinal peptide (VIP) in isolated porcine ophthalmic artery. Whilst ACh induced relatively rapid, endothelium-dependent dilation, CGRP and VIP induced slower dilations. Both CGRP and VIP were found to have partial endothelium-dependence in this artery. The simultaneous addition of ACh with CGRP potentiated the relaxation induced by CGRP, as has already been shown for substance P. ACh did not potentiate VIP relaxation, but the results generally indicate a potential role for ACh in initiating rapid dilation prior to strong, sustained relaxation by CGRP or VIP. The potential role of the endothelium and of substances like ACh or substance P in enhancing the rate of dilation of neuropeptides inducing strong and sustained relaxation is discussed.

Sumatriptan Relaxes Isolated Porcine Ophthalmic Artery, but Inhibits VIP-Induced Relaxation

Sumatriptan, a 5-hydroxytryptamine (5HT)1-like receptor agonist, is a new antimigraine drug which is also effective in cluster headache (CH), a disorder with marked ocular circulatory abnormalities. Sumatriptan could putatively exert a therapeutic effect in this vascular bed. The present study is an attempt to assess sumatriptans vasoactivity in isolated porcine ophthalmic artery (POA) and to verify whether it has similar activity to 5HT, and whether it interferes with the vasodilation induced by calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP). In contrast to 5HT, sumatriptan induced only slight contraction in POA at high concentrations. However, in some artery segments pre-contracted with PGF22a, sumatriptan induced a slight and short-lasting but marked relaxation. In addition, relaxations induced by VIP were inhibited significantly by sumatriptan, whereas CGRP effects were not influenced by the drug. Such reactions suggest that sumatriptans effect in CH is probably unrelated to direct ocular arterial vasoconstriction.

Low concentrations of lithium and cyclooxygenase inhibitors enhance endothelin-1 (ET-1)-induced contractions in human temporal artery, but not in porcine ophthalmic artery

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