Homocysteine levels in adolescent schizophrenia patients

Homocysteine is a sulfur containing amino acid that has been widely investigated for its putative role in cardiovascular and neuropsychiatric disorders. It has been suggested that homocysteine has implications especially in young, male schizophrenia patients. In this prospective case-control study, we compared plasma homocysteine levels in a group of adolescent schizophrenia inpatients (aged 14–21 years; n = 23) to normal healthy controls (n = 51). Mean plasma homocysteine levels were significantly higher in the patient group than in the control group (15.40 ± 2.00 and 9.78 ± 0.33 μmol/L, respectively, p < 0.032). The difference was almost entirely attributable to the male schizophrenia subgroup (18.18 ± 5.65 in male patients vs. 10.31 ± 5.33 μmol/L in female patients). The group × sex interaction was statistically significant (p = 0.0035). These data indicate that a subgroup of male adolescent schizophrenia patients has high homocysteine blood levels. The role of homocysteine in the pathophysiology of adolescent-onset schizophrenia merits further investigation.     

Further evidence of an association between adolescent bipolar disorder with smoking and substance use disorders: a controlled study

Although previous work suggests that juvenile onset bipolar disorder increases risk for substance use disorders and cigarette smoking, the literature on the subject is limited. We evaluated the association of risk for substance use disorders and cigarette smoking with bipolar disorder in adolescents in a case–control study of adolescents with bipolar disorder (n = 105, age 13.6 ± 2.5 years [mean]; 70% male) and without bipolar disorder (“controls”; n = 98, age 13.7 ± 2.1 years; 60% male). Rates of substance use and other disorders were assessed with structured interviews (KSADS-E for subjects younger than 18, SCID for 18-year-old subjects). Bipolar disorder was associated with a significant age-adjusted risk for any substance use disorder (hazard ratio[95% confidence interval] = 8.68[3.02 25.0], χ² = 16.06, p < 0.001, df = 1), alcohol abuse (7.66 [2.20 26.7], χ² = 10.2, p = 0.001, df = 1), drug abuse (18.5 [2.46 139.10], χ² = 8.03, p = 0.005, df = 1) and dependence (12.1 [1.54 95.50], χ² = 5.61, p = 0.02, df = 1), and cigarette smoking (12.3 [2.83 53.69], χ² = 11.2, p < 0.001, df = 1), independently of attention deficit/hyperactivity disorder, multiple anxiety, and conduct disorder (CD). The primary predictor of substance use disorders in bipolar youth was older age (BPD − SUD versus BPD + SUD, logistic regression: χ² = 89.37, p < 0.001). Adolescent bipolar disorder is a significant risk factor for substance use disorders and cigarette smoking, independent of psychiatric comorbidity. Clinicians should carefully screen adolescents with bipolar disorder for substance and cigarette use.     

Neurobehavioral performance in workers exposed to toluene

Toluene is widely used in adhesive, printing, painting and petroleum industries in many countries. This study was conducted to examine the effect of chronic exposure to toluene below 100 ppm on neurobehavioral performance using a computerized neurobehavioral test battery that emphasizes simple instructions and practice prior to testing. The Behavioral Assessment and Research System (BARS) with Korean language instructions was administered to 54 workers from three different industries: oil refinery, gravure printing, and rubber boat manufacturing. The battery consisted of the following tests: Digit Span (DS), Simple Reaction Time (SRT), Selective Attention (SAT), Finger Tapping (FT), and Symbol Digit (SD). Urine was collected at the end-of-shift to analyze urinary hippuric acid to assess exposure level to toluene. Based on the previous air toluene level, workers were divided into three groups: Low (21 workers, less than 10 ppm), Moderate (13 workers, 20–30 ppm) and High (20 workers, 70–80 ppm) exposure status. Analysis of Covariance (ANCOVA) adjusting for age, education and work duration as covariates, was performed to examine the relationship between the neurobehavioral performance and the exposure groups. Poorer performance of the High exposure group was found on FT-preferred (F = 7.034, p = 0.002) and SAT latency (F = 11.710, p = 0.000). Age showed a significant correlation with SD (r = 0.417, p = 0.002) and SAT number correct (r = −0.460, p = 0.000). Years of education and work duration were not significantly correlated with any items.

This study supports that toluene exposure below 100 ppm is associated with neurobehavioral changes and that high-level toluene exposure could cause not only attention and concentration, but also motor performance deficits.     

Changes of neurobehavioral and sensory functions due to toluene exposure below 50ppm?

Data of a follow up study with four examinations were summarized by odds ratio statistics in order to scrutinize the results of the earlier studies with cross sectional approaches.

For a “high”- (n = 106) and a “low”-exposed group (references, n = 86) current toluene exposures of 26 ppm versus 3 ppm and lifetime weighted average exposures of 45 ppm versus 9 ppm were ascertained. As measures of sensory functions vibration thresholds, colour discrimination, and auditory thresholds were used. Measures of psychological performances were attention (symbol–digit substitution, switching attention, simple reaction), memory (digit span forward, delayed reproduction of pictures), and psychomotor functions (steadiness, line tracing, aiming, tapping, peg board). Additionally, the frequency of diseases and symptoms were ascertained.

By odds ratio statistics including relevant cofactors no significant increase of “cases with impaired functions” among the high-exposed workers was found. Evidence for neurobehavioral effects due to long-term toluene exposure below 50 ppm was not established.     

Colour vision and contrast sensitivity losses of mercury intoxicated industry workers in Brazil

We evaluated vision loss in workers from fluorescent lamp industries (n = 39) who had retired due to intoxication with mercury vapour and had been away from the work situation for several years (mean = 6.32 years). An age-matched control group was submitted to the same tests for comparison. The luminance contrast sensitivity (CSF) was measured psychophysically and with the sweep visual evoked potential (sVEP) method. Chromatic red–green and blue–yellow CSFs were measured psychophysically. Colour discrimination was assessed with the Farnsworth–Munsell 100-hue test, Lanthony D-15d test and Cambridge Colour Vision Test. Patient data showed significantly lower scores in all colour tests compared to controls (p < .001). The behavioural luminance CSF of the patients was lower than that of controls (p < .001 at all frequencies tested). This result was confirmed by the electrophysiologically measured sweep VEP luminance CSF except at the highest frequencies—a difference that might be related to stimulus differences in the two situations. Chromatic CSFs were also statistically significantly lower for the patients than for the controls, for both chromatic equiluminant stimuli: red–green (p < .005) and blue–yellow (p < .04 for all frequencies, except 2 cycles per degree (cpd), the highest spatial frequency tested) spatial gratings. We conclude that exposure to elemental mercury vapour is associated with profound and lasting losses in achromatic and chromatic visual functions, affecting the magno-, parvo- and koniocellular visual pathways.     

The effect of DHEA complementary treatment on heroin addicts participating in a rehabilitation program: A preliminary study

We evaluated the effect of DHEA complementary treatment in opiate addicts undergoing detoxification. DHEA (100 mg/day) or placebo was added to the routine medication protocol in a randomized, double blind controlled study. Follow-up for 12 months was conducted. Two separate DHEA-treated subgroups were identified by the Fuzzy clustering method: one showed statistically significant improvement in the severity of withdrawal symptoms, depression and anxiety scores (n = 34; p < 0.001 for all) and the other subgroup deteriorated in all measures (n = 15). DHEA at the end of the detoxification program showed a tendency towards correlation with the duration of abstinence (r = 0.6843; p > 0.05; n = 6), while a negative correlation was obtained with the cortisol level (r = − 0.900; p = 0.005, n = 8). The completion-rate of the DHEA-improved subgroup was greater than in the DHEA-deteriorated subgroup (64.7% vs. 33.3%, respectively).

The influence of supplementary DHEA treatment was mostly effective in heroin addicts who had not previously used either cocaine or benzodiazepines and who had experienced only few withdrawal programs.     

Pregnancy outcome in women with inflammatory bowel disease following exposure to 5-aminosalicylic acid drugs: a meta-analysis

5-ASA drugs are commonly used for management of inflammatory bowel disease (IBD) during pregnancy. The safety of drug therapy for IBD during pregnancy is an important clinical concern. The present meta-analysis was performed to explore the risk of adverse pregnancy outcomes in women with IBD following exposure to 5-ASA drugs (mesalazine, sulfasalazine, balsalazide, and olsalazine). Bibliographic databases were searched upto June 2007 for studies investigating pregnancy outcomes in women with IBD following exposure to any 5-ASA drugs. The outcomes of interest were congenital abnormalities, stillbirth, spontaneous abortion, preterm delivery, and low birth weight. The odds ratios (OR) and confidence interval (CI) for the individual studies were pooled and heterogeneity analysis was performed. Seven studies with a total of 2200 pregnant women with IBD were included; 642 received 5-ASA drugs (mesalazine, sulfasalazine or olsalazine) and 1158 received no medication. The OR was found 1.16 (95% CI: 0.76–1.77, P = 0.57) for congenital abnormalities, 2.38 (95% CI: 0.65–8.72, P = 0.32) for stillbirth, 1.14 (95% CI: 0.65–2.01, P = 0.74) for spontaneous abortion, 1.35 (95% CI: 0.85–2.13, P = 0.26) for preterm delivery, and 0.93 (95% CI: 0.46–1.85, P = 0.96) for low birth weight.

In conclusion, this meta-analysis suggest that there is no more than an 1.16-fold increase in congenital malformations, an 2.38-fold increase in stillbirth, an 1.14-fold increase in spontaneous abortion, an 1.35-fold increase in preterm delivery, and an 0.93-fold increase in low birth weight.     

Sensitivity of fetus and pups to excess levels of maternal intakes of alpha linolenic acid at marginal protein levels in Wistar rats

There is growing interest in the role omega 3 fatty acids (n3), in promoting fetal growth. Present study examined whether alpha linolenic acid, primary vegetarian dietary omega 3 fatty acid source and precursor to cellular membrane phospholipid eicosapentaenoic acid and docosahexaenoic acid, can improve birth outcome. Pregnant dams from three groups (seven in each) were fed: control diet (18% protein with 7% soybean oil, normal alpha linolenic acid), or two treatment diets at marginal protein level of 12%; one with 7% soybean oil (Treatment I, normal alpha linolenic acid), and other with 3% flax oil and 4% soybean oil (Treatment II, four times normal alpha linolenic acid) during gestation. There was a reduction in litter size and litter weight (p < 0.05) at birth in the Treatment II group as compared to the Control group. Alpha linolenic acid (p < 0.05), eicosapentaenoic acid (p < 0.05) levels increased while arachidonic acid levels (p < 0.05) reduced in gastric milk at birth and blood at end of lactation in Treatment II as compared to Treatment I group. Brain fatty acid levels showed reduction (p < 0.05) only in docosahexaenoic acid levels in dams from Treatment I and Treatment II, at the end of lactation. Results suggest sensitivity of fetus and pups for excess levels of alpha linolenic acid ’in a diet at marginal protein level’.     

Low-level styrene exposure and color vision in Swedish styrene workers

Styrene exposure and color vision for 108 workers (21–65 years) was studied at Swedish reinforced plastic plants. Acute exposure was measured at work. Data on past exposures and personal background data were collected by questionnaire. Current exposure varied between 0.3 and 96 mg/m³. Cumulative past exposures varied from 18 to 4455 mg years/m³, and an index of lifetime weighted average exposure (LWAE) varied from 5 to 129 mg/m³. Color vision was tested using the Lanthony D15 desaturated panel binocularly without prior training in conditions with ample light (1400 lx). Color vision was slightly correlated to LWAE (r = 0.188, p = 0.052). Workers were divided into two exposure groups according to LWAE. Analyses of variance revealed effects on the Vingrys’ color vision confusion index (F = 6.04; p = 0.016) and total error (F = 6.296; p = 0.014). This study thus indicates that styrene exposure even at levels below the current Swedish OEL of 20 mg/m³ may affect color vision negatively.     

Phenolic content and antioxidant activities of white and purple juices manufactured with organically- or conventionally-produced grapes

Although the beneficial effects of moderate wine intake are well-known, data on antioxidant capacity of grape juices are scarce and controversial. The purpose of this study was to quantify total polyphenols, anthocyanins, resveratrol, catechin, epicatechin, procyanidins, and ascorbic acid contents in grape juices, and to assess their possible antioxidant activity. Eight Vitis labrusca juices – white or purple, from organically- or conventionally-grown grapes, and obtained in pilot or commercial scale – were used. Organic grape juices showed statistically different (p < 0.05) higher values of total polyphenols and resveratrol as compared conventional grape juices. Purple juices presented higher total polyphenol content and in vitro antioxidant activity as compared to white juices, and this activity was positively correlated (r = 0.680; p < 0.01) with total polyphenol content. These results indicate that white and purple grape juices can be used as antioxidants and nutritional sources.     

Manganese acts centrally to activate reproductive hormone secretion and pubertal development in male rats

Manganese (Mn) is an important element for normal growth and reproduction. Because Mn accumulates in the hypothalamus and is capable of stimulating puberty-related hormones in female rats, we assessed whether this metal could cause similar effects in male rats. We have demonstrated that MnCl₂, when administered acutely into the third ventricle of the brain, acts dose dependently to stimulate luteinizing hormone (LH) release. Furthermore, there was a dose dependent stimulation in the secretion of LH-releasing hormone (LHRH) from the medial basal hypothalamus in vitro, and administration of an LHRH receptor antagonist in vivo blocks Mn-induced LH release. To assess potential chronic effects of the metal, male pups were supplemented with 10 or 25 mg MnCl₂ per kg by gastric gavage from day 15 until days 48 or 55, at which times developmental signs of spermatogenesis were assessed. Results demonstrate that while significant effects were not observed with the 10 mg/kg dose, the animals receiving the 25 mg/kg dose showed increased LH (p < 0.05), FSH (p < 0.01) and testosterone (p < 0.01) levels at 55 days of age. Furthermore, there was a concomitant increase in both daily sperm production (p < 0.05) and efficiency of spermatogenesis (p < 0.05), demonstrating a Mn-induced acceleration in spermatogenesis. Our results suggest Mn is a stimulator of prepubertal LHRH/LH secretion and may facilitate the normal onset of male puberty. These data also suggest that the metal may contribute to male precocious pubertal development should an individual be exposed to low but elevated levels of Mn too early in life.     

Reversal of aminolevulinic acid dehydratase (ALAD) inhibition and reduction of erythrocyte protoporphyrin levels by Vitamin C in occupational lead exposure in Abeokuta, Nigeria

In order to investigate the toxic effects of lead during occupational exposure to this metal, the activity of aminolevulinic acid dehydratase (ALAD) and the concentrations of erythrocyte protoporphyrin (EPP) were determined in blood of various artisans in Abeokuta, Nigeria and these were related to blood lead levels. ALAD activity in the artisans was inhibited to varying extents. ALAD activity was inhibited to the tune of 77% in petrol station attendants while the lowest inhibition of 36% was obtained in the welders. EPP was also significantly increased in the artisans (p < 0.001). The highest EPP level of 241.57 ± 89.27 μg/100 ml of red blood cell was observed in upholsterers. A significant (p < 0.001) negative correlation was observed between ALAD activity and blood lead levels on one hand (r = −0.631) and between ALAD activity and EPP on the other hand (r = −0.461). Administration of a daily dose of 500 mg ascorbic acid for 2 weeks reversed the lead-induced inhibition of ALAD. Increased EPP levels observed in the artisans also responded positively to the ascorbic acid supplementation. A significant reduction (p < 0.001) in blood lead was also observed in the artisans at the end of the 2-week ascorbic acid therapy. Our findings indicate that ascorbic acid may offer more advantages over the conventional agents for the treatment of lead poisoning, especially in cases where the subjects cannot be removed from the source of lead exposure.     

Association between exposure to persistent organohalogen pollutants and epididymal and accessory sex gland function: multicentre study in Inuit and European populations

Exposure to persistent organochlorine pollutants (POPs) may have negative impact on male reproductive function. We, therefore, investigated the association between serum levels of POPs and epididymal and accessory sex gland function. Serum levels of CB-153, p,p′-DDE and seminal markers of epididymal [neutral- glucosidase (NAG)], prostatic [prostate specific-antigen (PSA)] and zinc, and seminal vesicle function (fructose) were measured from 135 Swedish fishermen and fertile men from Greenland (n = 163), Warsaw, Poland (n = 167) and Kharkiv, Ukraine (n = 158). Multiple linear regression analyses, adjusting for potential confounders, were employed using both continuous and categorized exposure variables. Both exposure and outcome variables were log transformed. Considering the consistency between models with either continuous or categorized CB-153 levels, negative associations with the activity of NAG were found among Greenlandic men (mean difference 7.0 mU/ejaculate, 95% CI 3.0, 34), and in the aggregated cohort (mean difference 4.0 mU/ejaculate, 95% CI −0.2, 8.0). A positive association was observed between CB-153 and PSA as well as zinc among Kharkiv men. In the Swedish cohort, a negative association was found between CB-153 and fructose. In conclusion, the negative effects of POP on sperm motility, observed in the same study population might partly be caused by post-testicular mechanisms, involving a decreased epididymal function.     

Antioxidant activity of the oyster mushroom, Pleurotus ostreatus, on CCl4-induced liver injury in rats

This study was undertaken to investigate the putative antioxidant activity of the oyster mushroom Pleurotus ostreatus on CCl₄-induced liver damage in male Wistar rats. Intraperitoneal administration of CCl₄ (2 ml/kg) to rats for 4 days resulted in significantly elevated (p < 0.05) serum levels of glutamic oxaloacetic transaminase (SGOT), glutamic pyruvate transaminase (SGPT) and alkaline phosphatase (SALP) compared to controls. In the liver, significantly elevated levels (p < 0.05) of malondialdehyde (MDA) and lowered levels (p < 0.05) of reduced glutathione (GSH) were observed following CCl₄ administration. Quantitative and qualitative analysis of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (Gpx) revealed lower activities of these antioxidant enzymes in the liver of CCl₄-administered rats. An analysis of the isozyme pattern of these enzymes revealed variations in relative concentration presumably due to hepatotoxicity. When rats with CCl₄-induced hepatotoxicity were treated with the extract of P. ostreatus, the serum SGOT, SGPT and SALP levels reverted to near normal, while the hepatic concentration of GSH, CAT, SOD and Gpx were significantly increased (p < 0.05) and that of MDA significantly (p < 0.05) lowered, when compared to CCl₄-exposed untreated rats. Histopathological studies confirmed the hepatoprotective effect conferred by the extract of P. ostreatus. These results suggest that an extract of P. ostreatus is able to significantly alleviate the hepatotoxicity induced by CCl₄ in the rat.     

Deramciclane in the treatment of generalized anxiety disorder: A placebo-controlled, double-blind, dose-finding study

Deramciclane, a camphor derivative, is a novel anxiolytic agent with a unique mechanism of action. It acts as a potent and specific antagonist at serotonin 5-HT_2A/2C receptors, and exhibits anxiolytic efficacy in animal models. The aim of this double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy, safety, and tolerability of a range of doses of deramciclane in patients with generalized anxiety disorder (GAD). Adult patients with a diagnosis of GAD (DSM-IV) and a Hamilton Anxiety Rating Scale (HAM-A) total score ≥ 18; a score ≥ 2 for the HAM-A items ‘Anxious Mood’ and ‘Tension’; a score ≥ 4 on the Clinical Global Impression of Severity of Illness (CGI-S) Scale; and a score ≤ 20 on the Montgomery–Åsberg Depression Rating Scale (MADRS) were enrolled in the study. Following a 1–2 week placebo run-in period, patients were randomized to receive deramciclane (10, 30, or 60 mg/day in two divided doses) or placebo for 8 weeks, followed by a 2-week placebo wash-out period. The primary efficacy measure was change in HAM-A score from baseline to week 8. Adverse events were monitored throughout the study. Withdrawal reactions were assessed at the end of the study (week 8) and during the placebo wash-out period using the Physician's Withdrawal Checklist (34 items). In the intent-to-treat population (n = 208), both the deramciclane 30 mg/day and 60 mg/day doses provided clinically relevant improvements in HAM-A total score after 8 weeks of treatment, reaching statistical significance compared with placebo in the 60 mg/day dose group (p = 0.024) and a clear trend in the 30 mg/day group (p = 0.059). On the HAM-A psychic anxiety factor, significant improvements were seen in patients in the deramciclane 30 mg/day and 60 mg/day treatment groups compared with those in the placebo group (p < 0.05). Adverse events were reported at a similar frequency across all four treatment groups; the most commonly reported adverse event was headache. No withdrawal reactions were observed on abrupt discontinuation of deramciclane. In conclusion, deramciclane 60 mg/day showed significant evidence of efficacy for the treatment of GAD in adult patients. The efficacy for the 30 mg/day dose was close to the larger dose although not significant in the primary analysis, and there was no significant evidence of efficacy for the 10 mg/day dose. Deramciclane was safe and well-tolerated up to the 60 mg/day dose over an 8-week period.     

Down syndrome time-clustering in January 1987 in Belarus: link with the Chernobyl accident?

The Chernobyl accident (April 26, 1986) exposed a large part of the Belarus population to ionizing radiation. We analyzed the time trends of Down syndrome (DS) in Belarus to evaluate whether either brief exposure at high dose rates during the plume passage or continuous exposure at low doses and dose rates of the residents of contaminated areas had any detectable impact on DS prevalence at birth. DS data came from the Belarus National Registry of Congenital Malformations (1981–2001). We observed a significant peak of DS in January 1987 (26 cases observed and 9.84 expected; observed/expected ratio = 2.64; 95% CI = 1.72–3.76), but found no positive long-term time trends in contaminated or control areas. The time occurrence of the January peak, high dose rates during the plume passage and experimental data showing a radiosensitive phase of oogenesis around conception time in mammals suggest that the January peak may be linked to the Chernobyl plume.     

Associations of polybrominated diphenyl ethers (PBDEs) in breast milk and dietary habits and demographic factors in Taiwan

The aim of this study was to examine levels of PBDEs in breast milk associated with seafood consumptions of Taiwanese mothers. Our participants were selected from healthy women recruited between December 2000 and November 2001 from a medical center in central Taiwan. The congeners of PBDEs in 20 milk samples were analyzed by a gas chromatograph with a high resolution mass detector. The mean level of BDE47 in breast milk from mothers with pre-pregnant BMI <22.0 kg/m² had a significantly higher magnitude compared to those with pre-pregnant BMI 22.0 kg/m² (1.59 vs. 0.995 ng/g lipid, p = 0.041). We did not find significant correlations between PBDEs exposure levels and women’s age, parity, blood pressure, annual household income, and education level. Women who ate more fish and meat did not show significantly higher PBDE levels than those who ate less, but a significant difference in PBDE levels was demonstrated between the higher (2.15 ng/g lipid) and lower (3.98 ng/g lipid) shellfish consuming subjects (p = 0.002) after an adjustment for the confounders. The ratios of PCB153/BDE47, PCB153/BDE153, and PCB153/PBDEs were significantly correlated with frequent consumption of fish and shellfish. The PCB153/BDE153 ratio was not associated with the other dietary habits (i.e. meat). The ratios of PCB153/PBDEs may therefore be a new indicator for exposure as a result of seafood consumption.     

Acute effects of low doses of methyl parathion on human EEG

Biological monitoring of workers exposed to organophosphates consists mainly of measuring serum or erythrocyte cholinesterase activity. However, animal experiments and a field study suggest that quantitative analysis of EEG may be more sensitive. In a parallel group design, 25 farmers were investigated, spraying methyl parathion or water for 50 min. EEG was recorded before and after spraying. Serum and erythrocyte cholinesterase activity was compared with intraindividual pre-exposure values. Plasma methyl parathion concentrations ranged up to 12.1 μg/l, methyl paraoxon was not detectable. Based on plasma concentrations, two exposed subgroups were defined. In EEG recorded with closed eyes, ₁-power increased insignificantly (Kruskal–Wallis test) in both subgroups. β₁-power was enhanced in both exposed subgroups, reaching significance (p ≤ 0.05) at five of 17 electrodes. Spearman's rank correlation showed a significant association between methyl parathion plasma concentration and the median of β₁-band power of the 17 electrodes (rho = 0.48, p = 0.015). Cholinesterase activity did not decrease. On a group basis, EEG is possibly more sensitive than cholinesterase. EEG changes suggest brain cholinesterase inhibition following low exposure to methyl parathion.     

Enhanced nasal absorption of hydrophilic markers after dosing with AT1002, a tight junction modulator

AT1002 is a six-mer synthetic peptide, H-FCIGRL-OH, that retains the delta G and Zot biological activity of reversibly opening tight junctions and increases the paracellular transport of drugs. The objective of this study was to evaluate the possible use of AT1002 in enhancing the nasal availability of macromolecules using large paracellular markers as model agents. Male Sprague–Dawley rats cannulated in the jugular vein were randomly assigned to receive radiolabelled paracellular markers, [¹⁴C]PEG4000 or [¹⁴C]inulin, with/without AT1002, for each intranasal study. The plasma concentration of PEG4000 with AT1002 (10 mg/kg) was significantly higher than that from PEG4000 control over 360 min following intranasal administration. The AUC_0–360 min and C_max from the PEG4000/AT1002 (10 mg/kg) treatment were statistically (p < 0.05) increased to 235% and 357%, of control, respectively. When inulin was administered with AT1002 (10 mg/kg), the plasma concentration was significantly higher (p < 0.05) than control over 360 min, and increases (p < 0.05) of 292% and 315% for AUC_0–360 min and C_max over control were observed, respectively. AT1002 significantly increased the nasal absorption of molecular weight markers, PEG4000 and inulin. This study suggests that AT1002 may be used to enhance the systemic availability of macromolecules when administered concurrently.     

Blood manganese concentrations and intrauterine growth restriction

To assess the relationship between blood concentrations of manganese (Mn) and intrauterine growth restriction (IUGR), Mn levels in the umbilical cord blood (UCB) and the mother whole blood (MWB) samples were measured in apparently healthy mothers and their newborns. Measurement was conducted by an inductively coupled plasma mass spectrometry. Manganese concentrations in MWB were significantly lower (p < 0.01) in IUGR cases than in appropriate for gestational age (AGA) cases (mean ± S.D.; 16.7 ± 4.8 and 19.1 ± 5.9 μg/l, respectively). Conversely, UCB concentrations of Mn were significantly higher (p < 0.05) in IUGR newborns than AGA newborns (44.7 ± 19.1 and 38.2 ± 13.1 μg/l, respectively). Logistic regression analysis demonstrated significant relationships of the mother whole blood and the umbilical cord blood concentrations of Mn in IUGR cases (OR = 0.868, 1.044, respectively). The study suggests that manganese concentrations in MWB and UCB might induce different effects on birth weight in healthy mothers. Because intrauterine growth restriction is a multi-factorial problem, further epidemiological and clinical studies on larger numbers of subjects are needed to confirm the findings in the present study.