Triheptanoin, an odd-medium-chain triglyceride, impacts brain cognitive function in young and aged mice.

ABSTRACTThe brain aging process triggers cognitive function impairment, such as memory loss and compromised quality of life. Cognitive impairment is based on bioenergetic status, with reduced glucose uptake and metabolism in aged brains. Anaplerotic substrates are reported to promote mitochondrial ATP generation, having been tested in clinical trials for the treatment of neurological disorders and metabolic diseases.Objectives and Methods: To assess whether the improvement in oxidative capacity ameliorates cognitive function in adults (12 weeks), and aged (22-month-old) C57/6BJ mice, they received (1) a ketogenic diet, (2) a ketogenic diet supplemented with the anaplerotic substance, triheptanoin, or (3) a control diet for 12 weeks. Spontaneous alternation and time spent in a previously closed arm in the Y-maze test and time interacting with an unknown object in the novel object recognition test (NORT) were used to evaluate working memory. Acetylcholinesterase (AChE) activity in the prefrontal lobe, brain left hemisphere, and cerebellum was also evaluated. Glucose transporter 3 (GLUT3) expression in the prefrontal lobe was analyzed by western blotting.Results: The ketogenic diet (KD) reduced spontaneous alternation in aged mice, leading to lower AChE activity in the aged prefrontal lobe and cerebellum, and in the parieto-temporal-occipital lobe of adult mice. Furthermore, KD decreased GLUT3 protein expression in the frontal lobe of the adults.Discussion: Supplementation of KD with triheptanoin prevented memory impairment and showed similar values of AChE activity and GLUT3 expression compared to the controls. Our data suggest that triheptanoin has a potential role in the bioenergetic capacity of the brain, improving cognitive function.

Effect of transcutaneous electrical nerve stimulation (TENS) on knee pain and physical function in patients with symptomatic knee osteoarthritis: the ETRELKA randomized clinical trial.

OBJECTIVE: To determine the effectiveness of TENS at relieving pain and improving physical function as compared to placebo TENS, and to determine its safety, in patients with knee osteoarthritis. METHODS: Multi-centre, parallel, 1:1 randomized, double-blind, placebo-controlled clinical trial conducted in six outpatient clinics in Switzerland. We included 220 participants with knee osteoarthritis recruited between October 15, 2012, and October 15, 2014. Patients were randomized to 3 weeks of treatment with TENS (n = 108) or placebo TENS (n = 112). Our pre-specified primary endpoint was knee pain at the end of 3-weeks treatment assessed with the WOMAC pain subscale. Secondary outcome measures included WOMAC physical function subscale and safety outcomes. RESULTS: There was no difference between TENS and placebo TENS in WOMAC pain at the end of treatment (mean difference -0.06; 95%CI -0.41 to 0.29; P = 0.74), nor throughout the trial duration (P = 0.98). Subgroup analyses did not indicate an interaction between patient/treatment characteristics and treatment effect on WOMAC pain at the end of treatment (P-interaction ≥0.22). The occurrence of adverse events was similar across groups, with 10.4% and 10.6% of patients reporting events in the TENS and placebo TENS groups, respectively (P = 0.95). No relevant differences were observed in secondary outcomes. CONCLUSIONS: TENS does not improve knee osteoarthritis pain when compared to placebo TENS. Therapists should consider other potentially more effective treatment modalities to decrease knee osteoarthritis pain and facilitate strengthening and aerobic exercise. Our findings are conclusive and further trials comparing TENS and placebo TENS in this patient population are not necessary.

Association between screen time and accelerometer-measured 24-h movement behaviors in a sample of Brazilian adolescents.

OBJECTIVES: Different screen time activities may be related to sleep, physical activity, and sedentary behavior. The objective was to examine the association between self-reported screen time activities and accelerometer-measured 24-h movement behaviors. STUDY DESIGN: This was a cross-sectional study. METHODS: Adolescents' (n = 718, 50.4% girls, 16 years) sleep duration, sedentary behavior, light-intensity physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) were estimated with wrist-worn accelerometry. Time spent on screen time activities related to studying, working, watching videos, playing video games, and using social media was self-reported. Multilevel linear regressions were used to test the association between screen time with sleep, sedentary behavior, and physical activity. RESULTS: Boys and girls slept 6.4 and 6.7 h per night, spent 10.4 and 10.1 h/d in sedentary behavior, spent 4.0 and 4.4 h/d in LPA, and spent 34.7 and 29.2 min/d in MVPA, respectively. Studying was inversely related to LPA and MVPA. Working was inversely related to sleep and positively related to LPA. Watching videos was associated with lower LPA and MVPA. For boys, videogames were associated with increased sedentary behavior and lower LPA and MVPA. For girls, studying and/or using social media were associated with lower LPA and MVPA. CONCLUSIONS: Indicators of screen time were associated with different accelerometer-measured 24-h movement behaviors in this sample of Brazilian adolescents.

Difficulty in detecting low levels of polymyxin resistance in clinical Klebsiella pneumoniae isolates: evaluation of Rapid Polymyxin NP test, Colispot Test and SuperPolymyxin medium.

Polymyxins are important therapeutic options for treating infections, mainly those caused by carbapenem-resistant Klebsiella pneumoniae. Specific chemical characteristics of polymyxins make it difficult to perform antimicrobial susceptibility testing, especially within the clinical laboratory. Here we aimed to evaluate the performance of three phenotypic methods: Rapid NP Polymyxin Test, ColiSpot test and the SuperPolymyxin medium. To accomplish this, 170 non-duplicate clinical K. pneumoniae isolates were analysed (123 colistin-resistant and 47 susceptible). The sensitivity and specificity obtained for Rapid Polymyxin NP Test, Colispot and SuperPolymyxin medium were, respectively, 90% and 94%, 74% and 100%, and 82% and 85%. Very major errors occurred more frequently in low-level colistin-resistant isolates (MICs 4 and 8 µg/mL). Rapid Polymyxin NP proved to be a method capable of identifying colistin-resistant strains in acceptable categorical agreement. However, major errors and very major errors of this method were considered unacceptable for colistin-resistance screening. Although the Colispot test is promising and easy to perform and interpret, the results did not reproduce well in the isolates tested. The colistin-containing selective medium (SuperPolymyxin) showed limitations, including quantification of mucoid colonies and poor stability. Nevertheless, Colispot and SuperPolymyxin medium methods did not present acceptable sensitivity, specificity and categorical agreement. It is essential to use analytical tools that faithfully reproduce bacterial resistance in vitro, especially in last-line drugs, such as polymyxins, when misinterpretation of a test can result in therapeutic ineffectiveness.

Impact of Selection Bias on Treatment Effect Size Estimates in Randomized Trials of Oral Health Interventions: A Meta-epidemiological Study.

Emerging evidence suggests that design flaws of randomized controlled trials can result in over- or underestimation of the treatment effect size (ES). The objective of this study was to examine associations between treatment ES estimates and adequacy of sequence generation, allocation concealment, and baseline comparability among a sample of oral health randomized controlled trials. For our analysis, we selected all meta-analyses that included a minimum of 5 oral health randomized controlled trials and used continuous outcomes. We extracted data, in duplicate, related to items of selection bias (sequence generation, allocation concealment, and baseline comparability) in the Cochrane Risk of Bias tool. Using a 2-level meta-meta-analytic approach with a random effects model to allow for intra- and inter-meta-analysis heterogeneity, we quantified the impact of selection bias on the magnitude of ES estimates. We identified 64 meta-analyses, including 540 randomized controlled trials analyzing 137,957 patients. Sequence generation was judged to be adequate (at low risk of bias) in 32% ( n = 173) of trials, and baseline comparability was judged to be adequate in 77.8% of trials. Allocation concealment was unclear in the majority of trials ( n = 458, 84.8%). We identified significantly larger treatment ES estimates in trials that had inadequate/unknown sequence generation (difference in ES = 0.13; 95% CI: 0.01 to 0.25) and inadequate/unknown allocation concealment (difference in ES = 0.15; 95% CI: 0.02 to 0.27). In contrast, baseline imbalance (difference in ES = 0.01, 95% CI: -0.09 to 0.12) was not associated with inflated or underestimated ES. In conclusion, treatment ES estimates were 0.13 and 0.15 larger in trials with inadequate/unknown sequence generation and inadequate/unknown allocation concealment, respectively. Therefore, authors of systematic reviews using oral health randomized controlled trials should perform sensitivity analyses based on the adequacy of sequence generation and allocation concealment.

Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts.

BACKGROUND: Subclinical hyperthyroidism (SHyper) has been associated with increased risk of hip and other fractures, but the linking mechanisms remain unclear. OBJECTIVE: To investigate the association between subclinical thyroid dysfunction and bone loss. METHODS: Individual participant data analysis was performed after a systematic literature search in MEDLINE/EMBASE (1946-2016). Two reviewers independently screened and selected prospective cohorts providing baseline thyroid status and serial bone mineral density (BMD) measurements. We classified thyroid status as euthyroidism (thyroid-stimulating hormone [TSH] 0.45-4.49 mIU/L), SHyper (TSH < 0.45 mIU/L) and subclinical hypothyroidism (SHypo, TSH ≥ 4.50-19.99 mIU/L) both with normal free thyroxine levels. Our primary outcome was annualized percentage BMD change (%ΔBMD) from serial dual X-ray absorptiometry scans of the femoral neck, total hip and lumbar spine, obtained from multivariable regression in a random-effects two-step approach. RESULTS: Amongst 5458 individuals (median age 72 years, 49.1% women) from six prospective cohorts, 451 (8.3%) had SHypo and 284 (5.2%) had SHyper. During 36 569 person-years of follow-up, those with SHyper had a greater annual bone loss at the femoral neck versus euthyroidism: %ΔBMD = -0.18 (95% CI: -0.34, -0.02; I2 = 0%), with a nonstatistically significant pattern at the total hip: %ΔBMD = -0.14 (95% CI: -0.38, 0.10; I2 = 53%), but not at the lumbar spine: %ΔBMD = 0.03 (95% CI: -0.30, 0.36; I2 = 25%); especially participants with TSH < 0.10 mIU/L showed an increased bone loss in the femoral neck (%Δ BMD = -0.59; [95% CI: -0.99, -0.19]) and total hip region (%ΔBMD = -0.46 [95% CI: -1.05, -0.13]). In contrast, SHypo was not associated with bone loss at any site. CONCLUSION: Amongst adults, SHyper was associated with increased femoral neck bone loss, potentially contributing to the increased fracture risk.

An in vivo study on bone formation behavior of microporous granular calcium phosphate.

This study was developed based on in vivo investigation of microporous granular biomaterials based on calcium phosphates, involving matrices of ß-tricalcium phosphate (ß-TCP), hydroxyapatite (HA), biphasic compositions of both phases and a control group. The physicochemical characterization of materials was carried out by X-Ray diffraction (DRX) and mercury porosimetry. Biodegradability, bioactivity and neoformation processes were investigated by Raman spectroscopy, scanning electron microscopy (SEM) and polarized light conducted on biopsies obtained from in vivo tests for periods of 90 and 180 days. These were performed to evaluate the behavior of granular microporous compositions in relation to bone neoformation. Through the performance obtained from in vivo assays, excellent osseointegration and bone tissue neoformation were observed. The results are encouraging and show that the microporous granular biomaterials of HA, ß-TCP and biphasic compositions show similar results with perfect osseointegration. Architectures simulating a bone structure can make the difference between biomaterials for bone tissue replacement and repair.

Malnutrition increases NO production and induces changes in inflammatory and oxidative status in the distal colon of lactating rats.

BACKGROUND: Epidemiological studies have indicated the lack of breast feeding as a risk factor associated with later development of inflammatory bowel disease. Nevertheless, the repercussion of little feeding during suckling on large intestine inflammatory response and anti-oxidant resources has not yet been completely understood. This study hypothesized that unfavorable lactation is able to induce oxidative stress and release of inflammatory mediators modifying the integrity of the colon epithelium in weanling rats. METHODS: Wistar rats were reared under different early nutritional conditions according to litter size in two groups: N6 (6 pups/dam) and N15 (15 pups/dam) until the 25th postnatal day. The distal colon was removed and processed for biochemical, morphometric, and immunohistochemical analyzes. Lipoperoxidation, nitric oxide (NO), reduced (GSH) and oxidized (GSSG) glutathione, tumor necrosis factor-alpha (TNF-α), interleukins-1ß, 4 and 10 (IL-1ß; IL-4; IL-10) levels, and total superoxide dismutase (tSOD), and catalase (CAT) activities were assessed. Morphometric analysis was carried out using paraffin sections and wholemount myenteric plexus preparations. KEY RESULTS: Increased lipoperoxidation, NO, TNF-α and IL-1b levels, reduced tSOD and increased CAT activities were found in the N15 compared to N6 group. No intergroup difference was detected for IL-10, while lower levels of IL-4, GSH and GSSG and lower neuronal size and density were induced by undernutrition. CONCLUSIONS & INFERENCES: Reduced feeding during suckling changed the inflammatory response and oxidative status in the colon of weanling rats. These data suggest potential mechanisms by which malnutrition early in life may increase the vulnerability of the large intestine to insults.

Vitis labrusca leaf extract prevents pentylenetetrazol-induced oxidative damage but not seizures in rats.

Epilepsy is a disorder of the central nervous system characterized by recurrent seizures. It is a very common disease in which approximately 30% of patients do not respond favorably to treatment with anticonvulsants. Oxidative stress is associated with neuronal damage arising from epileptic seizures. The present study investigated the possible anticonvulsant and antioxidant effects of a leaf extract of Vitis labrusca in an animal model of seizures induced by pentylenetetrazole (PTZ). The animals received injections of V. labrusca extract (10, 30 and 100 mg/kg) or vehicle and, 30 minutes later, they received an injection of PTZ, and were then observed for 30 minutes. The latency time and tonic—clonic seizure time were registered. Oxidative damage in lipids and proteins was quantified in the cerebellum, cerebral cortex and hippocampus. It was observed that the leaf extract were capable of reducing lipid peroxidation and protein oxidation caused by PTZ at all doses tested.

A critical period for omega-3 nutritional supplementation in the development of the rodent visual system.

Retinocollicular connections form precise topographical maps that are normally completed through the selective elimination of misplaced axons and the stabilization of topographically ordered axon terminals during early development. Omega-3 fatty acids, acquired exclusively through the diet, and its main metabolite, docosahexaenoic acid (DHA), are involved in brain development and synaptic maturation. We have previously shown that the nutritional restriction of omega-3/DHA results in abnormal retinocollicular topographical fine-tuning. Therefore, we studied the role of omega-3 fatty acids nutritional supplementation and the developmental time windows during which this postnatal supplementation would restore normal topographical maps in the visual system. Female rats and their litters were chronically fed with either control (soy oil) or restricted omega-3 (coconut oil) diets. Fish oil supplementation was introduced between either postnatal day (PND) 7-13, PND7-28 or PND21-42. At PND13, PND28 or PND42, animals received an anterograde eye injection of a neuronal tracer to visualize retinocollicular axons. Confirming previous observations we found that an omega-3/DHA deficiency resulted in an abnormally high innervation density of retinal axons at the visual layers of the superior colliculus (SC). Although a short-term fish oil supplementation between PND7-13 could not restore normal retinocollicular topography, an extended treatment between PND7-28 completely recovered normal innervation densities of retinotectal axons. However, a late onset supplementation protocol, between PND28-42, was no longer effective in the restoration of the abnormal topographical pattern induced by an early omega-3 nutritional malnutrition. The results suggest a critical period for omega3/DHA dietary intake for the proper development of visual topographical maps.

Placental expression of eNOS, iNOS and the major protein components of caveolae in women with pre-eclampsia.

Caveolae regulate many cardiovascular functions and thus could be of interest in relation to pre-eclampsia, a pregnancy specific disorder characterised by hypertension and proteinuria. We examined placental mRNA and protein expression/localisation of the caveolae components Caveolin 1-3, Cavin 1-4 as well as eNOS/iNOS in normotensive control (n = 24) and pre-eclamptic pregnancies (n = 19). Placental mRNA expression of caveolin-1, cavin 1-3, was lower and eNOS expression was increased in pre-eclampsia (P < 0.05 for all). Additionally Caveolin-1 protein expression was also reduced in pre-eclampsia (P = 0.007); this could be an adaptive response in pre-eclampsia, possibly to attenuate the oxidative stress/inflammation.

Absorbable collagen membranes for periodontal regeneration: a systematic review.

Guided tissue regeneration (GTR) with bioabsorbable collagen membranes (CM) is commonly used for the treatment of periodontal defects. The objective of this systematic review of randomized clinical trials was to assess the clinical efficacy of GTR procedures with CM, with or without bone substitutes, in periodontal infrabony defects compared with that of open flap debridement (OFD) alone. Primary outcomes were tooth loss and gain in clinical attachment level (CAL). Screening of records, data extraction, and risk-of-bias assessments were performed by two reviewers. Weighted mean differences were estimated by random effects meta-analysis. We included 21 reports on 17 trials. Risk of bias was generally high. No data were available for the primary outcome tooth loss. The summary treatment effect for change in CAL for GTR with CM compared with OFD was 1.58 mm (95% CI, 1.27 to 1.88). Despite large between-trial heterogeneity (I2 = 75%, p < .001), all trials favored GTR over OFD. No differences in treatment effects were detected between trials of GTR with CM alone and trials of GTR with CM in combination with bone substitutes (p for interaction, .31). GTR with CM, with or without substitutes, may result in improved clinical outcomes compared with those achieved with OFD alone. Our findings support GTR with CM for the treatment of infrabony periodontal defects.

PP040. Expression of RANTES (CCL5) in maternal plasma, fetal plasma and placenta in pre-eclampsia and normotensive controls.

INTRODUCTION: Studies have shown pre-eclampsia (PE) as an exacerbation of gestational inflammatory process. RANTES (Regulated upon Activation, Normal T-cell Expressed, and Secreted)/CCL5 is a chemokine, which is involved in chronic inflammation by the recruitment of inflammatory cells. It is secreted by many cell types such as endothelial cells, smooth muscle cells, macrophages, platelets and activated T-cells. Thus we hypothesized that RANTES expression is altered in PE and may be different in gestational tissues (maternal plasma, fetal plasma and placenta). OBJECTIVES: The purpose of the study is to analyze the expression of RANTES (CCL5) in three different tissues: maternal plasma, fetal plasma and placenta, in PE and normotensive controls (NC). METHODS: PE was diagnosed by the National High Blood Pressure Education Program Working Group Report on High Blood Pressure in Pregnancy guidelines. The patients were assisted in the São Lucas Hospital from PUCRS, Porto Alegre, Brazil. Following ethical approval and informed written consent, maternal and umbilical plasma and placental biopsies were taken from 33 PE and 35 NC. Samples were centrifuged immediately after blood collection and plasma was stored at -80°C until assay. Placental Biopsies were taken midway between the cord and periphery, from the central region of cotyledons and were stored as well. RANTES expression was made by the ELISA test, in duplicates. They were also analyzed in each group: maternal age, maternal parity, gestational age on delivery, glucose, body mass index, proteinúria creatinuria ratio, systolic blood pressure (SBP), diastolic blood pressure (DBP), delivery method, birth weight, placental weight and Apgar index in 1st and 5th minute. RESULTS: Maternal age at the time of blood collection was not significantly different between the two groups. The women with preeclampsia delivered earlier and had smaller babies compared with the controls. Significant associations between groups (p<0.001) were seen in SBP, DBP, birth weight and delivery method. RANTES was increased in maternal plasma and placenta in patients with PE and decreased in fetus plasma in the same group (p<0.001). CONCLUSION: In this study, we have shown that RANTES expression in maternal plasma and placenta tissues, in women with established pre-eclampsia, is higher than in gestation-matched women with a healthy pregnancy. It confirms the hypotheses that physiology of PE is associated with an increase of normal gestational inflammatory process. However in fetus tissue, the inflammatory chemokine is decreased in PE women. FUNDING: CAPES Foundation, Ministry of Education of Brazil, Brasília - DF 70040-020, Brazil.

PP050. Distribution of ABO and Rhesus blood groups in patients withpre-eclampsia.

INTRODUCTION: The ABO-system of antigens and the Rh-system (D-antigen) is genetically determined and remains the most important blood group systems clinically. Several studies have examined the association between ABO and Rhesus blood group systems and pre-eclampsia. At present there is no consensus to define this association, especially not in a Brazilian population. OBJECTIVES: The purpose of the present study was to evaluate the association between pre-eclampsia versus ABO and Rhesus blood group systems in pregnant women hospitalized in a University Hospital in Porto Alegre, Brazil -Hospital São Lucas (HSL). METHODS: Pre-eclampsia/eclampsia (PE/E) was diagnosed by the National High Blood Pressure Education Program Working Group Report on High Blood Pressure in Pregnancy guidelines. This study consisted of 14,894 pregnant women admitted to the Maternity Department between 2005 and 2010. The patients were reviewed retrospectively for inclusion. Complications in pregnancy not related to pre-eclampsia/eclampsia (PE/E) and those with uncompleted data were excluded. Medical records of 410 women were used to diagnose PE/E. The control group consisted of 8781 women. Each group was subdivided according to their blood groups. RESULTS: In comparison to the PE/E women and controls, no specific relation in blood groups was observed. With respect to ABO and Rh groups, no differences between PE/E and controls were observed (P=0.479 and P=0.169 respectively). When analyzed with both Rh and ABO Pearson Chi-Square also showed no differences (P=0.569). CONCLUSION: This study aimed to demonstrate some association between blood groups and PE/E using a large sample from the south of Brazil, a population not investigated before. In our study, no specific differences were observed between PE/E and controls in the distribution of the blood groups. In conclusion, the results of this study suggest no association between ABO and Rhesus blood group systems and PE/E in our population. FUNDING: CAPES Foundation-Ministry of Education of Brazil.

Stimulation of prostaglandin EP2 receptors on RGC-5 cells in culture blunts the negative effect of serum withdrawal.

Reduced neurotrophic support is one possible cause for retinal ganglion cells dying in glaucoma. Experiments were designed to investigate the effect of EP2 receptor agonist butaprost on transformed retinal ganglion (RGC-5) cells where reduced neurotrophic support was simulated by serum withdrawal. Cultures were analysed for cell viability, flow cytometry, reactive oxygen species and apoptosis. Western blot and immunohistochemistry were used to provide information for the occurrence of PGE(2) receptor-types. We demonstrated the existence of all four types of PGE(2) receptors in RGC-5 cells and exposure of cultures to butaprost resulted in an elevation of cAMP. Serum deprivation induced RGC-5 cell death was significantly attenuated by butaprost as well as by rolipram and forskolin where intracellular cAMP levels were increased. These data are of value in relation to the possible use of EP2 receptor agonists to reduce both elevated intraocular pressure and retinal ganglion cell death as occurs in glaucoma.

Effects of naphthalene and phenanthrene on visual and prey capture endpoints during early stages of the dourado Salminus brasiliensis.

Naphthalene (NAP) and phenanthrene (PHE) effects on Salminus brasiliensis, a carnivorous freshwater fish, were investigated using behavioral tests. Larval stages of S. brasiliensis were exposed to water concentrations of 0, 0.04 mg/l, 0.20mg/l and 0.50mg/l for naphthalene and 0, 0.01 mg/l, 0.05 mg/l and 0.1mg/l for phenanthrene during two developmental phases. The prey fish Prochilodus lineatus were not exposed. Visual acuity was measured at the end of phase 2 in individual S. brasiliensis, which were also tested at the end of each phase for number of attacks on prey, number of prey captured, prey capture efficiency, and distance swam. Vision was impaired by PHE exposure, as acuity angles increased in exposed fish. At Stage I 2.3+/-1.2 prey were captured with 46% efficiency in controls compared to 0.4+/-0.3 prey captured with 13.4% efficiency in fish exposed to 0.05 mg PHEl(-1), the LOEL for both endpoints. At Stage II 4.0+/-1.1 preys were captured in controls compared to 2.5+/-0.9 preys captured in fish exposed to 0.01 mg PHEl(-1), the LOEL. Stage II control fish captured prey with 70% efficiency compared to 30% efficiency at Stage II fish exposed to 0.05 mg PHEl(-1), the LOEL. Distance swam was not affected by either NAP or PHE exposure. The exposure of larval stages of S. brasiliensis to realistic water concentrations of PHE impairs foraging skills and could affect recruitment of the species.

Increased serum phosphodiesterase activity in women with pre-eclampsia.

OBJECTIVE: To measure the activity of serum phosphodiesterase (PDE) in pre-eclampsia. DESIGN: Case-control study. SETTING: Nephrology Laboratory and Obstetrics Unit at São Lucas Hospital from Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil. SAMPLE: Twenty-nine normal and 28 pregnant women with pre-eclampsia. METHODS: Serum was collected from women with pre-eclampsia, at the time of diagnosis, and from gestation-matched controls. Circulating PDE activity was assessed by measuring consumption of the substrate thymidine 5'-monophosphate p-nitrophenyl ester and expressed as PDE units/l. MAIN OUTCOME MEASURES: Serum PDE Activity. RESULTS: Mean substrate consumption was higher in pre-eclamptic condition (V(max)= 15.8 +/- 1.4 versus 12.7 +/- 0.9 U/L, P= 3.7 x 10(-14)). CONCLUSION: These data suggest that altered PDE activity may play a role in pre-eclampsia endothelial dysfunction.

Differential vulnerability of the rat retina, suprachiasmatic nucleus and intergeniculate leaflet to malnutrition induced during brain development.

We investigated in young rats the effects of malnutrition on the main structures of the circadian timing system: retina, hypothalamic suprachiasmatic nuclei (SCN), thalamic intergeniculate leaflet, retinohypothalamic- and geniculohypothalamic tracts. Control rats were born from mothers fed a commercial diet since gestation, and malnourished rats from mothers fed a multideficient diet since gestation (GLA group) or lactation (LA group). After weaning, pups received the same diet as their mothers, and were analysed at postnatal days 27, 30-33 and 60-63. Brain sections were processed to visualise in the SCN neuropeptide Y immunoreactivity and terminal labeling after intraocular tracer injections. Nissl staining was used to assess cytoarchitectonic boundaries of the SCN and cell features in retinal whole mounts. Cell counts, morphometric and densitometric analysis were performed. Compared with controls, the total retinal surface was reduced and the topographical distribution of retinal ganglion cells was altered in malnourished rats, with changes in their density. Alterations were also detected in the SCN dimensions in the GLA and LA groups at one and two postnatal months, as well as in the SCN portion occupied by the retinal input in the GLA group at days 30-33, but not in the NPY-containing geniculohypothalamic tract. The present data point to subtle changes, with a low and differential vulnerability to early malnutrition, of structures involved in circadian timing regulation. Furthermore, the present findings suggest that the altered circadian rhythmicity previously documented in malnourished rats cannot be ascribed to impaired development of the retino- and geniculohypothalamic projections to the SCN.