Larval growth rate is associated with the composition of the gut microbiota in the Glanville fritillary butterfly.

The rapidly increasing body of literature on commensal microbiota has revealed a large phylotypic and functional diversity of microbes associated with vertebrates and invertebrates. In insects, the gut microbiota plays a role in digestion and metabolism of the host as well as protects the host against pathogens. In the study reported here, we sampled gut microbiota of the larvae of the Glanville fritillary butterfly (Melitaea cinxia). The larvae were collected from the field or reared in the laboratory. This butterfly has two host plant species, Plantago lanceolata and Veronica spicata, and the host plant species is known from previous studies to influence larval growth rate. However, our results demonstrate that about 50 % of the variation in larval growth rate can be attributed to the effect of the gut microbial composition plus the joint effect of microbiota and the host plant species, while host plant species alone makes no significant contribution. Our results support previous studies showing that diet influences the gut microbiota but, more unexpectedly, that the composition of the gut microbiota significantly influences larval growth rate. We suggest that host plant effects on larval growth and development observed in many previous studies may be mediated via the gut microbiota. While we measured the growth rate only in laboratory-reared larvae, the similarity of the gut microbial composition between samples from field-collected and laboratory-reared larvae suggests that the results can be generalized to natural conditions.

CT angiographic analysis of carotid artery stenosis: comparison of manual assessment, semiautomatic vessel analysis, and digital subtraction angiography.

BACKGROUND AND PURPOSE: To compare multisection CT angiography (CTA) analyzed with source/maximum intensity projection (MIP) images as well as semiautomated vessel analysis software with intra-arterial digital subtraction angiography (DSA) in detection and grading of carotid artery bifurcation stenosis. METHODS: Consecutive patients with sonography evidence of a marked internal carotid artery stenosis underwent both carotid CTA and DSA (37 patients, 73 vessels). In CTA, the grade of stenosis was determined using axial source and MIP images as well as vessel analysis. The scans were blind-analyzed by 2 neuroradiologists using the NASCET criteria. RESULTS: Correlation of CTA source/MIP images versus DSA estimates of stenosis (R = 0.95) was higher than for the vessel analysis method versus DSA (R = 0.89). Compared with DSA, CTA source/MIP images underestimated high (78.2% versus 86.4%, P < .05) and moderate grades of stenosis (57.3% versus 63.1%, P < .05) to a lesser extent than the vessel analysis method (68.5% versus 83.5% and 51.8% versus 63.1%, P < .05). For a high-grade stenosis, sensitivity and specificity of source/MIP image CTA were 75% and 96%, respectively, whereas for the vessel analysis method, they were 47% and 96%, respectively. For moderate stenosis, the source/MIP image CTA sensitivity and specificity were 88% and 82%, respectively, and for vessel analysis method, 62% and 82%, respectively. CTA detected all 4 occlusions. CONCLUSION: In evaluation of carotid stenosis, CTA provides an adequate, less invasive alternative with a high correlation to conventional DSA, though it tends to underestimate clinically relevant grades of stenosis. Its accuracy is not improved by semiautomated analysis. The data support the use of CTA in confirming carotid occlusion.

Monitoring the CNS pathology in aspartylglucosaminuria mice.

Aspartylglucosaminuria (AGU) is a recessively inherited lysosomal storage disorder caused by the deficiency of the aspartylglucosaminidase (AGA) enzyme. The hallmark of AGU is slowly progressing mental retardation but the progression of brain pathology has remained uncharacterized in humans. Here we describe the long-term follow-up of mice carrying a targeted AGU-mutation in both alleles. Immunohistochemistry, histology, electron microscopy, quantitative magnetic resonance imaging (MRI) and behavioral studies were carried out to evaluate the CNS affection of the disease during development. The lysosomal storage vacuoles of the AGA -/- mice were most evident in central brain regions where MRI also revealed signs of brain atrophy similar to that seen in the older human patients. By immunohistochemistry and MRI examinations, a subtle delay of myelination was observed in AGA -/- mice. The life span of the AGA -/- mice was not shortened. Similar to the slow clinical course observed in human patients, the AGA -/- mice have behavioral symptoms that emerge at older age. Thus, the AGU knock-out mice represent an accurate model for AGU, both histopathologically and phenotypically.

Place cell rigidity correlates with impaired spatial learning in aged rats.

In humans and in animals, some aged individuals are severely impaired in learning and memory capacity whereas others perform as well as young adults. In the present study, the spatial memory capacity of young and aged rats was characterized by the Morris water maze task, and then firing patterns of hippocampal "place cells" were assessed as the animals explored a familiar environment and a geometrically-altered version of the environment. Spatial representations of hippocampal cells in young and memory-intact aged rats changed upon exposure to the altered environment. In contrast, spatial representations of many cells in aged, memory-impaired rats were unaffected by the environmental alteration. Furthermore, combining all groups, the extent to which spatial representations distinguished the familiar and altered environments predicted learning capacity in the water maze. These findings suggest that a major component of memory impairment in aging may be the failure of the hippocampus to encode subtle differences in contextual information that differ across multiple experiences, such as the sequence of training trials in the water maze.

Diffuse amyloid deposition, but not plaque number, is reduced in amyloid precursor protein/presenilin 1 double-transgenic mice by pathway lesions.

Alzheimer's disease (AD) is the most common form of dementia in the elderly, and the characteristic pathological hallmarks of the disease are neuritic plaques and neurofibrillary tangles. The sequence of events leading to the extracellular deposition of amyloidbeta (Abeta) peptides in plaques or in diffuse deposits is not clear. Here we investigate the relation between disrupted axonal transport of amyloid precursor protein (APP) and/or Abeta and the deposition of Abeta in the deafferented terminal fields in APP/presenilin 1 double-transgenic AD-model mice. In the first experiment we ablated entorhinal cortex neurons and examined the subsequent changes in amyloid deposition in the hippocampus 1 month later. We show that there is a substantial reduction in the amount of diffuse amyloid deposits in the denervated areas of the hippocampus. Further, to investigate the effects of long-term deafferentation, in a second experiment we cut the fimbria-fornix and analyzed the brains 11 months post-lesion. Diffuse amyloid deposits in the deafferented terminal fields of area CA1 and subiculum were dramatically reduced as assessed by image analysis of the Abeta load. Our findings indicate that neuronal ablations decrease diffuse amyloid deposits in the terminal fields of these neurons, and, further, that pathway lesions similarly decrease the amount of diffuse amyloid deposits in the terminal fields of the lesioned axons. Together, this suggests that the axonal transport of APP and/or Abeta and subsequent secretion of Abeta at terminals plays an important role in the deposition of Abeta protein in Alzheimer's disease, and, further, that diffuse deposits do not develop into plaques.py>

Altered auditory-evoked potentials in mice carrying mutated human amyloid precursor protein and presenilin-1 transgenes.

Transgenic mice carrying human APPswe and PS1-A264E transgenes (A/P mice) have elevated levels of the highly fibrillogenic amyloid Abeta(1-42) (Abeta) and develop amyloid plaques around the age of 9 months. Our aim was to find whether the gradual accumulation of Abeta in these mice can be detected with long-term recording of auditory-evoked potentials. The A/P double-mutant mice had impaired auditory gating and a tendency toward increased latency of the cortical N35 response, but these changes were not age-dependent between 7 and 11 months of age. In a control experiment that included also APP and PS1 single-mutant mice, the A/P double-mutant mice had weaker auditory gating than either APP or PS1 mice. In contrast, increased N35 latency was found in both A/P and APP mice compared with nontransgenic or PS1 mice. The Abeta40 and Abeta42 levels were robustly increased in A/P mice and Abeta40 moderately increased also in APP mice. Plaques were deposited only in A/P mice. We conclude that the impaired auditory gating is associated with the overproduction Abeta42 but does not reflect its amount. In contrast, increased N35 latency is related to the APP genotype independent of Abeta42 production.

D-cycloserine, a partial NMDA receptor-associated glycine-B site agonist, enhances reversal learning, but a cholinesterase inhibitor and nicotine has no effect.

The present study examined the efficacy of single and combined treatments with an anticholinesterase, tetrahydroaminoacridine, nicotine and a glycine-B site partial agonist, D-cycloserine, in alleviating the water maze reversal learning defect induced by a medial septal lesion. D-cycloserine (3 and 10 mg/kg) improved reversal learning. Tetrahydroaminoacridine (1 and 3 mg/kg) and nicotine (0.1 and 0.3 mg/kg) had no effect on reversal learning. A combination of tetrahydroaminoacridine 3 mg/kg or nicotine 0.3 mg/kg and D-cycloserine 10 mg/kg was not more effective than D-cycloserine 10 mg/kg alone in improving reversal learning. This suggests that stimulation of NMDA mechanisms may more effectively improve in medial septal-lesioned rats reversal learning processes than stimulation of cholinergic activity.

Tetrahydroaminoacridine, a cholinesterase inhibitor, and D-cycloserine, a partial NMDA receptor-associated glycine site agonist, enhances acquisition of spatial navigation.

The present study examines the efficacy of single and combined treatments with an antiocholinesterase, tetrahydroaminoacridine (THA, i.p.), and a glycine-B site partial agonist, D-cycloserine (DCS, i.p.) to alleviate water maze (WM) spatial navigation defect induced by medial septal (MS) lesion. THA 3 and DCS at 3 or 10 mg/kg improved acquisition of the WM test, but only DCS improved spatial bias. These drugs had no effect on consolidation. A combination of THA 3 and DCS 10 mg/kg enhanced WM acquisition more effectively than either of the treatments on their own. This suggests that combined modulation of acetylcholine and NMDA mechanisms may have greater therapeutic effect to stimulate cognitive dysfunctions.

Effects of apamin on memory processing of hippocampal-lesioned mice.

We investigated the effects of acute i.p. injections of the Ca(2+)-dependent K(+) channel blocker, apamin, on water maze spatial navigation and radial arm maze performance in mice with partial hippocampal-lesions. In the radial arm maze, apamin 0.06 and 0.2 mg/kg dose-dependently reversed the lesion-induced defect. In the water maze, apamin 0.2 mg/kg alleviated the defect, but a lower dose 0.06 mg/kg was ineffective. At a higher dose, 0.4 mg/kg, apamin impaired the water maze performance. These results suggest that Ca(2+)-dependent K(+) channel blockers can alleviate the spatial reference memory and working memory impairment induced by partial hippocampal lesions.

Apamin improves spatial navigation in medial septal-lesioned mice.

We investigated the effects of acute i.p. injections of the Ca2+-dependent K+ channel blocker, apamin, on water maze spatial navigation, Y-maze and passive avoidance behavior in intact and medial septal-lesioned mice. Apamin 0.02, 0.06 or 0.2 mg/kg (i.p.) administered 30 min before or immediately after the training did not affect the performance of intact mice. Apamin 0.02 or 0.06 mg/kg (i.p.) administered immediately after the daily training did not affect the performance of medial septal-lesioned mice. Apamin 0.02 and 0.06 mg/kg (i.p.) administered 30 min before daily training reversed the navigation failure present in medial septal-lesioned mice during the initial and reversal learning stages of the water maze task. Apamin had no effect on the cognitive performance in Y-maze or passive avoidance tests. The results indicate that blockade of Ca2+-dependent K+ channels may facilitate acquisition of spatial navigation performance, but has no effect on consolidation, inhibitory avoidance and spontaneous alternation behavior in mice.

Tetrahydroaminoacridine and D-cycloserine fail to alleviate the water maze spatial navigation defect induced by hippocampal inactivation.

The present study examined the efficacy of single and combined treatment with an anticholinesterase, tetrahydroaminoacridine (i.p.), and a glycine-B site partial agonist, D-cycloserine (i.p.; a positive allosteric modulator of NMDA receptors), in alleviating the deficit in water maze spatial navigation induced by electrolytic lesion of the medial septum or lidocaine infusion into the dorsal hippocampi. In medial septum-lesioned rats, a combination of tetrahydroaminoacridine 3 mg kg(-1) and D-cycloserine 10 mg kg(-1) facilitated acquisition of the water maze test more effectively than either of the drugs alone. Single or combined treatment with tetrahydroaminoacridine 3 mg kg(-1) and D-cycloserine 10 mg kg(-1) had no effect on the water maze deficit induced by hippocampal lidocaine infusion. These results suggest that combined treatment with tetrahydroaminoacridine and D-cycloserine can effectively stimulate water maze spatial navigation, and that functioning of the hippocampus is a prerequisite for this effect.

Characterization of learning and memory behaviors and the effects of metrifonate in the C57BL strain of mice.

In the near future, a number of transgenic mouse models with neuropathological characteristics of Alzheimer's disease are expected to become widely available. It will be important to characterize their behavior in models for learning and memory. As a first step, we have characterized normal, medial septal-lesioned and hippocampal-lesioned C57BL mice, in different behavioral tests, i.e., water maze spatial navigation, Y-maze and passive avoidance behavior. These experiments were complemented by an investigation of the effects of acute treatment with an acetylcholinesterase inhibitor, metrifonate, in these behavioral tests. Normal C75BL mice perform very well in the water maze and the Y-maze, but suboptimally in the passive avoidance task. Lesioning of the medial septum or the dorsal hippocampus clearly impaired the performance of the mice. In medial septal-lesioned mice, metrifonate stimulated spatial navigation and alleviated the loss of activity in the Y-maze and passive avoidance. In hippocampal-lesioned mice, metrifonate had no effect on spatial navigation. It is concluded that C75BL mice are useful for testing in classical models for learning and memory, and that septohippocampal pathology is very likely to induce cognitive deficits in some of these models.

Plasma chain-breaking antioxidants in preterm infants with good and poor short-term outcome.

Many complications of prematurity have been suggested to result from free radical generation and an inadequacy of antioxidative capacity. We measured the plasma total peroxyl radical-trapping capability (TRAP) and concentrations of the main chain-breaking antioxidants contributing to it, i.e. uric acid, ascorbic acid, alpha-tocopherol, protein sulfhydryl groups and bilirubin, in 21 preterm infants with a mean birth weight of 1440 g and gestational age of 30 wk. The infants were divided into two groups according to their short-term outcome; the good outcome group (GOG) (N = 11) with no signs of morbidity and the poor outcome group (POG) (N = 10) with intraventricular haemorrhage and/or bronchopulmonary dysplasia and/or retinopathy. Arterial blood samples were obtained 3 and 10 days postpartum. TRAP was measured with a chemiluminescent method. As a comparison, venous blood samples from 13 adults (aged from 18 to 34) were used. At day 3 the poor outcome group had significantly higher TRAP than the good outcome or control group, mainly because of elevated uric acid concentration. Also the concentration of unidentified antioxidants was significantly lower in GOG. By day 10 the TRAP decreased substantially in both groups. However, from the components of TRAP, both ascorbate and the unidentified fraction decreased more in POG (p = 0.017 and 0.021, respectively). Furthermore in POG on day 10 urate concentration did not significantly differ from day 3 values. In conclusion, in preterm infants high TRAP was associated with high plasma uric acid concentration and a poor short-term prognosis.

Renal follow up of premature infants with and without perinatal indomethacin exposure.

AIMS: To evaluate early childhood renal growth, structure, and function in children born at less than 33 weeks gestation and to investigate possible independent effects of perinatal indomethacin exposure. METHODS: A total of 66 children born at less than 33 weeks gestation, 31 of them with perinatal indomethacin exposure (study group) and 35 without (control group), were examined at 2-4 years of age. Serum cystatin C and protein; plasma creatinine, sodium, and potassium; urine protein, calcium:creatinine ratios, and alpha(1) microglobulin; and glomerular filtration rate (GFR) were determined. Renal sonography examinations were performed. RESULTS: The mean serum cystatin C concentrations were slightly higher in the control group than in the study group. Mean values of serum protein, and plasma creatinine and sodium did not differ between the groups, neither did median plasma potassium concentrations and urine protein:creatinine and calcium:creatinine ratios. None had tubular proteinuria. Abnormal GFR (<89 ml/min/1.73 m(2)) was found in one case in each group and renal structural abnormalities in five in each group. In logistic regression analysis the duration of umbilical artery catheter (UAC) use and furosemide treatment emerged as the significant independent risk factors for renal structural abnormalities. Furosemide treatment and assisted ventilation remained the risk factors associated with renal abnormalities in general-that is, functional and/or structural abnormal findings. CONCLUSION: Perinatal indomethacin does not seem to affect long term renal growth, structure, or function in children born at less than 33 weeks gestation. Duration of UAC use, furosemide treatment, and assisted ventilation may be correlated with later renal structural and functional abnormalities.

Effects of metrifonate on the hippocampal theta rhythm of freely moving intact and MS-lesioned mice.

Changes in hippocampal electroencephalogram (EEG) have been suggested to be closely associated with spatial learning ability. Spatial learning can be improved in medial septal (MS)-lesioned mice by metrifonate, a cholinesterase inhibitor. We designed this study to investigate the effects of metrifonate on the hippocampal theta oscillation of intact and MS-lesioned mice. Intact and MS-lesioned C57BL mice were treated with acute injections of metrifonate (doses: 15, 50 and 100 mg/kg ip). These included a dose that considerably improved spatial memory of MS-lesioned mice in our earlier study. In addition, subtype selective muscarinic agents, BIBN-99, AF267B and AF150(S) were used. Recordings of hippocampal theta during movement and awake immobility revealed a dramatic reduction of theta in the lesioned animals. Metrifonate induced prominent changes in the EEG of intact mice, but not of MS-lesioned mice. The effect of metrifonate was not mimicked by two selective M(1)-agonists and was augmented by a combined injection of a selective M(2)-antagonist. These data suggest that improved spatial learning by the cholinesterase inhibitor metrifonate is unrelated to its effects on the hippocampal EEG. These two effects may be mediated through different muscarinic receptor subtypes.

Cord blood concentrations of vitamin A in preterm infants.

Plasma vitamin A concentrations were measured in cord blood samples from 56 infants of gestational ages < 33 weeks. Outcome was followed prospectively. Mothers' dietary habits and use of multivitamins during pregnancy were evaluated by means of a questionnaire. Vitamin A concentrations less than 1.05 micromol/l (low) were measured in 22, but levels below 0.7 micromol/l (deficient) only in two cases. The concentrations were not correlated with the infants' gestational ages. Infants with low concentrations were significantly more often multiplets compared to those with normal levels and the vitamin A concentrations of the multiplets were significantly lower than those of the singletons. The outcome measures used and the mothers' dietary habits and multivitamin use were similar in cases with low and normal vitamin A concentrations. Multiple gestation seems to be correlated with low plasma vitamin A concentrations in preterm infants at birth, and a complete assessment of vitamin A status to detect possible deficiency might be indicated in these cases.

Frequency and risk factors in bronchopulmonary dysplasia in a cohort of very low birth weight infants.

Frequency and perinatal risk factors in bronchopulmonary dysplasia (BPD) were retrospectively evaluated in a cohort of 242 infants with birth weights less than 1501 g born in one hospital in 1990-1994. At 28 days' postnatal age, 30.7% (59/192) of the infants alive received oxygen supplementation and showed typical radiological changes in chest X-rays. At 36 weeks' corrected gestation, 13.0% (24/184) of the survivors fulfilled these criteria. In multivariate analysis, low birth weight and gestational age, male sex, packed red cell infusions and long duration of ventilator therapy were correlated with an increased risk of BPD at 28 days' postnatal age. Only 49% of the infants with BPD had had respiratory distress syndrome, and 49% of them recovered from BPD by 36 weeks' corrected gestational age. Preeclampsia, low birth weight, rapid birth weight recovery, packed red cell infusions, long duration of ventilator therapy, patent ductus arteriosus and hyperoxia were associated with BPD beyond 36 weeks' corrected gestation. No infant born small for gestational age recovered from BPD before 36 weeks' corrected gestation. The frequency of BPD at 28 days' postnatal age seems to be increasing, but half of the patients recover before term. Factors other than respiratory distress syndrome, especially small birth weight, early weight gain and possibly intrauterine growth retardation are becoming more important risk factors of BPD beyond 36 weeks' corrected gestation.

Placenta as an indicator of fetal postnatal prognosis.

468 placentas were studied microscopically and by gross examination. Velamentous insertion of the umbilical cord, placenta circumvallate, retroplacental hematoma in connection with ablation of the placenta, and cord prolapse were found to be causative factors in asphyxia of the newborn. The increased placental weight was characteristic in maternal diabetes, hepatosis and, sometimes, in cases of infant malformations and specific inflammations. So-called embryonal persistence was often found histologically in these changes. Small fibrous placentas and those with ramification defects were commonly encountered among cases of toxemia and prolonged gestation. Microscopical placental maturation defects were not indicative of the fetal condition. Thus, only the changes found at gross examination appeared to be a significant indicator of the fetal prognosis.

Perinatal indomethacin treatment and neonatal complications in preterm infants.

UNLABELLED: To evaluate the incidence of neonatal complications among infants exposed to indomethacin antenatally, postnatally or both ante-and postnatally (combined), the records of 240 infants of gestational ages between 23 to 32 weeks were analysed retrospectively. Antenatal indomethacin treatment for longer than 2 days with a daily or cumulative dosage >/=150 mg correlated with a significantly higher incidence of grade I-II intraventricular haemorrhage. Combined exposure, cumulative antenatal exposure >/=150 mg and duration of antenatal exposure of more than 2 days was associated with necrotising enterocolitis and a cumulative exposure with sepsis. There was no independent association between indomethacin exposure and pneumothorax, bronchopulmonary dysplasia or respiratory distress syndrome. CONCLUSION: Preterm infants with exposure to antenatal indomethacin might be at increased risk of grade I and II intraventricular haemorrhage and those with both ante- and postnatal exposure at an increased risk of necrotising enterocolitis and sepsis.