Cytoprotective actions of 2,4-dimethoxybenzylidene anabaseine in differentiated PC12 cells and septal cholinergic neurons

The potential cytoprotective actions of a novel nicotinic agent 2,4-dimethoxybenzilidene anabaseine (DMXB) were investigated in differentiated PC12 cells and transected rat septal cholinergic neurons in vivo. In NGF-differentiated PC12 cells, removal of both NGF and serum led to cell loss, a reduced % of cells expressing neurites, the release of lactate dehydrogenase, and a decrease in total cellular protein. Cell loss was apparent within 24 h, and remained constant between 4–8 days post-NGF removal. NGF alone (100 ng/ml), DMXB (10 μM), but not nicotine (10 μM), prevented these cell and neurite losses. DMXB-induced cytoprotection was blocked by 1 μM mecamylamine. DMXB (1 mg/kg, ip) injected twice but not once per day protected cholinesterase-staining septal neurons from retrograde degeneration following unilateral fimbrial transections. The twice per day DMXB injection-protocol also decreased cell roundness among cholinesterase-staining cells in the lesioned septal hemisphere compared to saline-injected animals. These studies suggest that DMXB may exert cytoprotective activity in NGF-sensitive neuronal populations. © 1994 Wiley-Liss, Inc.     

Gastro-duodenal digestion products of the major peanut allergen Ara h 1 retain an allergenic potential

BACKGROUND: The process of gastro-duodenal digestion may play a role in determining the allergenic properties of food proteins. The sensitizing and allergenic potential of digestion products of highly degraded allergens, such as the major peanut allergen Ara h 1, is currently under debate. We evaluated the effect of in vitro gastro-duodenal digestion of Ara h 1 on T cell reactivity and basophil histamine release. METHODS: An in vitro model of gastro-duodenal digestion was used to investigate changes in the allergenic properties of Ara h 1 using in vitro assays monitoring T cell reactivity (proliferation, cytokine production) and histamine release of basophils from peanut allergic individuals. The digestion process was monitored using an SDS-PAGE gel. RESULTS: In vitro gastric digestion led to rapid degradation of Ara h 1 into small fragments M(r) L5600. Gastric digestion did not affect the ability of Ara h 1 to stimulate cellular proliferation. Gastro-duodenal digestion significantly reduced its ability to stimulate clonal expansion (P<0,05; Wilxocon's signed rank test). The Th-2 type cytokine polarization of T cells from peanut allergic donors (IFN-gamma/IL-13 ratio and IFN-gamma/IL-4 ratio of CFSE(low) CD4(+) T cells) remained unchanged regardless of the level of digestion. Histamine release of basophils from peanut allergic individuals was induced to the same extent by native Ara h 1 and its digestion products. CONCLUSION: Gastro-duodenal digestion fragments of Ara h 1 retain T cell stimulatory and IgE-binding and cross-linking properties of the intact protein.     

Early rapid weight gain and current overweight in relation to asthma in adolescents born with very low birth weight

Early catch-up growth and subsequent overweight are suggested to be associated with later cardiovascular diseases and later type II diabetes. However, the impact of early catch-up growth and childhood overweight on the development of asthma has been less studied, particularly in children born with very low birth weight (VLBW). A birth cohort of 74 VLBW children (birth weight < or = 1500 g) was followed from birth and investigated on asthma at 12 yr of age. Early rapid weight gain was in one way defined as an increase of weight > or =1 standard deviation score (SDS) at 6 months of corrected postnatal age. Current overweight was defined by body mass index (BMI) exceeding 21.2 and 21.7 kg/m(2), respectively, for boys and girls at 12 yr of age. Current asthma was diagnosed by a pediatrician, according to asthma ever in combination with a positive response to hypertonic saline bronchial provocation test and/or wheeze at physical examination at 12 yr old. Being overweight at 12 yr of age was associated with an increased risk for current asthma in the VLBW children [crude odds ratio (OR): 5.5, 95% confidence interval (CI): 1.3-22.2]. After adjustment for early weight gain and neonatal risk, the OR of overweight increased nearly three times (adjusted OR: 15.3, 95% CI: 2.5-90.6). Early rapid weight gain seemed to be inversely associated with current asthma (adjusted OR: 0.49 for an increase of weight equal to 1 SDS, 95% CI: 0.23-1.02, p = 0.06). In addition, early rapid weight gain was inversely associated with the magnitude of bronchial responsiveness at 12 yr (coefficient -1.15, p < 0.01). There was a strong and positive association between overweight and asthma at 12 yr of age in the VLBW children. This strong association had been reduced by early rapid weight gain, possibly via the reduction of bronchial responsiveness.     

The electrophysiological properties of substantia nigra pars compacta neurones recorded from 6-hydroxydopamine lesioned guinea-pigs in vitro

Summary Intracellular recordings were made from substantia nigra pars compacta neurones in vitro from animals with partial unilateral 6-hydroxydopamine lesions of the nigrostriatal tract. Lesions were assessed and grouped according to the severity of the strital dopamine depletion. No differences were seen between neurones from control and lesioned side nigrae as regards their membrane properties, firing rates, burst activity or percentage of quiescent neurones in any of the lesioned categories. It is concluded that following partial lesioning, the remaining substantia nigra zona compacta neurones in vitro, are functioning normally.     

Before-birth climatologic data may play a role in the development of allergies in infants

While an exacerbation in allergic symptoms corresponding to seasons has long been reported, few studies have investigated the association between the season of birth and allergic disorders. The aim of this study was to investigate whether the climatologic data before and after birth affected the incidence of atopic dermatitis (AD) and the results of allergy-related blood tests in early infancy. From February 1995 to January 2000, 2136 infants were tested for AD and followed for 12 months. AD patients were tested by using allergy-related blood tests. Data were compared according to the month of birth and the climatologic data using a computed statistical software package. Six hundred and thirty infants had AD before 12 months old, and significant differences were found according to the season of birth (p < 0.0001). Infants born in spring showed the lowest (22.3%) incidence, while those born in autumn showed the highest (34.6%). In 369 patients, total serum IgE levels, and serum specific IgE levels with egg white at 3 months old were also different according to the season of birth. All of these levels were lower in patients born in spring and summer, and higher in patients born in autumn and winter. Furthermore, the cumulative sunshine amount during the 3 months before and after birth was inversely correlated, while the average temperature over the 3 months before birth was positively correlated to the incidence of AD according to the month of birth. The climatologic data around birth may play an important role in whether an infant develops allergies.     

Adipokines in cord blood and risk of wheezing disorders within the first two years of life

BACKGROUND: Adipokines are involved in the regulation of many inflammatory processes and are present at very high concentrations in cord blood of term infants. OBJECTIVE: We analysed data of a large prospective birth cohort study to examine whether adiponectin and leptin concentration in cord blood are determinants of wheezing disorders in children within the first 2 years of life. METHODS: Seven hundred and forty mothers and their newborns were included in this analysis. Adiponectin and leptin concentrations were measured in cord blood. The cumulative incidence of physician-reported asthma or obstructive bronchitis was recorded during a 2-year follow-up. RESULTS: During the first 2 years of life, asthma or obstructive bronchitis was reported by the caring paediatricians for 157 (19.6%) of the children. We found a strong interaction of cord blood adiponectin and history of atopic disease in the mother with respect to the risk of physician-reported asthma or obstructive bronchitis (P=0.006). Compared with children with cord blood levels in the middle quintile (reference category), the odds ratios for physician-reported asthma or obstructive bronchitis in the bottom quintile and top quintile were 0.14 [95% confidence interval (CI) 0.02-0.90] and 2.12 (95% CI 0.67-6.66), respectively (P for trend=0.0003), among children of mothers with a history of atopy. This association was independent of other established risk factors. Leptin levels in cord blood were not associated with risk of asthma or obstructive bronchitis. CONCLUSIONS: In children of mothers with a history of atopy, concentrations of adiponectin in cord blood could play an important role in determining risk of wheezing disorders in early childhood.     

Hypertrophy of medial globus pallidus and substantia nigra reticulata in 6‐hydroxydopamine‐lesioned rats treated with L‐DOPA: Implication for L‐DOPA‐induced dyskinesia in Parkinson's disease

The medial globus pallidus plays a crucial role in generation of L‐DOPA‐induced dyskinesia in patients with Parkinson's disease. The 6‐hydroxydopamine‐lesioned rat exhibiting behavioral sensitization to L‐DOPA is one useful animal model for examining L‐DOPA‐induced dyskinesia. To determine neuropathological abnormality responsible for behavioral sensitization, the medial globus pallidus and the substantia nigra reticulata in 6‐hydroxydopamine‐lesioned rats treated with L‐DOPA were examined. Intermittent L‐DOPA treatment induced hypertrophy of the lesioned‐side of medial globus pallidus and substantia nigra reticulata of 6‐hydroxydopamine‐lesioned rats with behavioral sensitization to L‐DOPA. Additionally, coadministration of a 5‐HT_1A receptor agonist, 8‐hydroxy‐2(di‐n‐propylamino)tetralin with L‐DOPA, alleviated the hypertrophy with improvement of the behavioral sensitization. These results suggest that hypertrophy of the medial globus pallidus and substantia nigra reticulata is associated with induction of behavioral sensitization to L‐DOPA in 6‐hydroxydopamine‐lesioned rats. Therefore, neuropathological changes corresponding to hypertrophy might underlie L‐DOPA‐induced dyskinesia in patients with Parkinson's disease.     

Effect of amyloid peptides on the increase in TrkA receptor expression induced by nicotine in vitro and in vivo

The ability of nicotine to induce a cytoprotective or neuroprotective action occurs through several down-stream mechanisms. One possibility is that the drug increases the expression of tyrosine kinase A (TrkA) nerve growth factor (NGF) receptors. Certain β-amyloid peptides (e.g., Aβ1–42) have been shown to bind with high affinity to α7 nicotinic receptors and thus interfere with a potentially neurotrophic influence. Treatment of differentiated PC-12 cells with nicotine produced a concentration-dependent increase in cell-surface TrkA receptors that occurred concomitantly with cytoprotection. The effect of nicotine was blocked by either of the α7 receptor antagonists α-bungarotoxin (α-BTX) or methyllycaconatine. The cytoprotective action of nicotine also was inhibited by pretreatment with 10–100 nM Aβ1–42. Nicotine also was administered (four injections of 30 μg, spaced evenly over 24 h) to rats by direct injection into a lateral cerebral ventricle. Brain TrkA expression was increased significantly in hippocampus and entorhinal cortex (up to 32% above control), with no changes found in cerebral cortex or hypothalamus. The nicotine-induced increases in TrKA expression in hippocampus and entorhinal cortex were significantly inhibited by 10 μg α-BTX or by 10 nmol Aβ1–42. Therefore, physiologically relevant concentrations of Aβ1–42 can prevent nicotine-induced TrkA receptor expression in brain regions containing cholinergic neurons susceptible to the neurotoxicity associated with Alzheimer’s disease.     

短暂性脑缺血发作患者血浆中TXB2和PGF1α含量检测

本文用放射免疫法测定47例短暂性脑缺血发作(TIA)患者血浆中血栓素B_2(TXB_2)和6酮-前列腺F_(1α)(PGF_(1α))的含量。结果发现TIA患者血浆中TXB_2含量增高,PGF_(1α)降低;头颅CT或MRI示有小灶性梗塞者及TIA发作持续时间长于30min者TXB_2升高和PGF_(1α)降低更显著。治疗3个月后,血浆PGF_(1α)显著增高。TXB_2和PGF_(1α)在体内的失平衡是急性脑血管疾病发病的重要机理之一。