Behavioral changes are not directly related to striatal monoamine levels, number of nigral neurons, or dose of parkinsonian toxin MPTP in mice

Behavioral analyses of mice intoxicated by the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) have generated conflicting results. We therefore analyzed the relationship between behavioral changes, loss of monoamine levels, and loss of dopaminergic cell bodies in groups of mice intoxicated with acute or subchronic MPTP protocols. Despite a higher degree of neuronal loss in the mice intoxicated using subchronic protocols, dopamine loss was severe and homogeneous in the striatum in all groups. Dopamine levels were less severely reduced in the frontal cortex in the three groups of MPTP-intoxicated mice. Norepinephrine and serotonin levels in the striatum were decreased only in the mice intoxicated with the acute protocol. The most surprising result was that the mice intoxicated with the subchronic protocols were more active than the saline-treated mice. As reported in rats with dopamine depletion in the prefrontal cortex, the hyperactivity observed in our mice could be due to the reduced dopamine levels detected in this structure.     

A randomized, double-blind, double-dummy, parallel-group, multicenter, dose-reduction trial of the minimal effective doses of budesonide and fluticasone dry-powder inhalers in adults with mild to moderate asthma

BACKGROUND: Inhaled corticosteroids are established first-line anti-inflammatory treatment for asthma. Clinical trials comparing inhaled corticosteroids must take into consideration that because of their excellent effect at low doses, they typically induce a near-maximal response in asthma patients. OBJECTIVE: The aim of the present dose-response study was to estimate the minimal effective doses (MEDs) of budesonide and of fluticasone propionate via dry-powder inhaler in adults with mild to moderate asthma. METHODS: This was a randomized, double-blind, double-dummy, parallel-group, multicenter, dose-reduction trial performed in adults to compare these 2 inhaled corticosteroids. After a 4- to 6-week run-in period with beclomethasone dipropionate 2000 pg/d, patients fulfilling defined criteria for asthma control were randomly allocated to treatment with budesonide or fluticasone, both administered BID at a total of 800 pg/d. At 5-week intervals, the dose was reduced to 400 and then 200 pg/d (200 and 100 pg BID) if asthma control was maintained according to further defined criteria. The MED was defined as the last dose level before deterioration of asthma control. RESULTS: Subjects were 197 asthmatic patients with a mean age of 40.6 years in the budesonide group and 41.5 years in the fluticasone group. In both groups, baseline mean forced expiratory volume in 1 second (FEV(1)) was 79.4% of the predicted normal volume and baseline mean FEV(1) reversibility was 22.3%. The median MED for both groups was 400 microg/d, with no detectable difference in dis-tributions. The budesonide-to-fluticasone ratio for the geometric mean MED was 123% (95% CI, 99-153 [not significant]). No statistically significant differences regarding lung function, symptom scores, or rescue medication usage were found between the treatment groups during the first treatment period. Adverse-event profiles were similar in both groups, and no unexpected adverse events were considered to be caused by the study drugs. CONCLUSION: This effect-controlled study did not detect a statistically significant difference between the MEDs for budesonide and fluticasone via dry-powder inhaler in adults with mild to moderate asthma.     

Involvement of adrenal medulla grafts in the open field behavior

Immunohistochemical and behavioral techniques were used to study the effects of adrenal medulla grafts, implanted in striatum after bilateral kainic acid (KA) lesions of this structure, on the open field behavior of mice. KA-induced behavioral changes in leaning, grooming and locomotor activity of the open field test were significantly improved after grafting of the adrenal medulla, and in some respects, fully restored. Immunohistochemical identification showed that grafts contained neuron-like cells with a tyrosine hydroxylase (TH), phenylethanolamine N-methyltransferase, gamma-aminobutyric acid (GABA), choline acetyltransferase (ChAT), and enkephalin-like immunostainings. A likely interpretation of this complex pattern of results is that adrenal medullary grafts may restore the deficits of GABAergic neurons which in turn reverse the abnormalities in emotionality and locomotion. Neurobiologically, these behavioral improvements probably involve GABAergic and catecholaminergic factors of adrenal medulla grafts, although other neuroactive substances, such as acetylcholine and enkephalins, cannot be excluded.     

A semantic-based kernel for advanced health information systems

This paper reports on the design and development of an infrastructure allowing one to share and exchange multimedia data in the context of a health network. A single technology exploiting a semantic model of the hospital universe provides users with information and data of diverse origins, generated by the various actors or departments of the health organization. Functions provided include act management and patient record management governed by domain semantics. The functionality has been validated through laboratory experiments against the requirements of protocol directed care and health networks. The functionality is integrated into a clinician workstation exploited in the Internet/Intranet environment thanks to a commercial browser. These results have been obtained with the support of several projects in the frame of the Health-Care Telematics Applications Programme of the European Community and of the Eurêka Programme.     

银杏叶制剂对心绞痛患者的抗氧化和抗脂质过氧化作用

目的：探讨银杏叶制剂对心绞痛患者的抗氧化和抗脂质过氧化作用。方法：检测了７８例心绞痛患者经银杏叶制剂“天宝宁”治疗前后的血浆维生素Ｃ（Ｐ－ＶＣ）、维生素Ｅ（Ｐ－ＶＥ）、β－胡萝卜素（Ｐ－β－ＣＡＲ）、过氧化脂质（Ｐ－ＬＰＯ）以及红细胞超氧化物歧化酶（Ｅ－ＳＯＤ）、过氧化氢酶（Ｅ－ＣＡＴ）、谷胱甘肽过氧化物酶（Ｅ－ＧＳＨ－ＰＸ）、过氧化脂质（Ｅ－ＬＰＯ）值。结果：与治疗前比较,治疗后的Ｐ－ＶＣ、Ｐ－     

Genetic alterations in early-onset invasive breast carcinomas: correlation of c-erbB-2 amplification detected by fluorescence in situ hybridization with p53 accumulation and tumor phenotype.

p53 tumor-suppressor gene mutation and p53 protein over-expression have been reported with higher frequency in early-onset breast carcinomas (EOBC). Given the role attributed to normal p53 protein in DNA-repair mechanisms, other somatic genomic alterations would be expected to be associated with this abnormality. Amplification of the c-erbB-2 (HER-2/neu) oncogene and over-expression of the corresponding p185erbB-2 protein have been linked to prognosis and response to therapy in breast cancer. In a retrospective study of 62 formalin-fixed paraffin-embedded invasive EOBC (diagnosed at 35 years or less), the amplification status of the c-erbB-2 gene detected by fluorescence in situ hybridization (FISH) using a unique sequence probe was compared with p53 protein accumulation measured by immunohistochemistry (IHC) and phenotypic features. p185erbB2-protein expression was also detected by immunohistochemistry, together with estrogen-receptor (ER) and progesterone-receptor (PR) expression. The data for a sub-set of 33 node-negative EOBC cases were compared with 70 node-negative tumors diagnosed in women above 36 years of age. Compared with node-negative BC in older women, node-negative EOBC was significantly more likely to feature high grade, high proliferation rate, negative ER and/or PR and p53 over-expression (p < 0.05). A trend toward a higher incidence of c-erbB-2 amplification in EOBC (21% vs. 9%) reached near-significance (p = 0.07). In EOBC, c-erbB-2 amplification and p53 over-expression were not associated with high tumor grade or high cell-proliferation rate, in contrast to the significant associations of these markers in tumors in older women. Abnormalities in tumor markers, including c-erbB-2 gene amplification and p53-protein over-expression, occur at different rates in women with EOBC as compared with BC developing in older women. This finding may reflect a different pathogenesis for EOBC, and warrants further investigation.     

Physical sequelae and self-perceived attachment in adult survivors of childhood cancer.

The association between the physical sequelae of childhood cancer and self-reported attachment behavior was investigated in 97 adult survivors. Attachment was assessed using standardized self-report questionnaires. Functional disability and cosmetic sequelae of the cancer and its treatment were evaluated by the attending oncologist using a standardized rating scale. Results suggest that attachment is not significantly associated with physician-rated physical sequelae, but may be related to the time of onset of the functional deficits, independent of the current age or age at diagnosis. Further, survivors with functional sequelae in adulthood describe themselves as more insecure in their relationships in general and more ambivalent in their relationship with their parents. These findings, if replicated, suggest that the duration of the functional deficits as well as the developmental stage of the individual when they began may be important variables which affect the survivor's capacity to develop and maintain intimate relationships that are secure and satisfying.     

Development of HPLC method for Cyclopia subternata phenolic compound analysis and application to other Cyclopia spp.

Analysis of phenolic compounds in Cyclopia spp. (honeybush) is very important because of commercial interest in the plant material as an herbal tea and in extracts for the nutraceutical and cosmeceutical markets. An existing HPLC-DAD method was adapted and proved reproducible as evidenced by good intra- and inter-day precision. The method allows the quantification of several well-known as well as unidentified phenolic compounds. Its suitability for quantification of the major phenolic compounds present in the water extracts of unfermented and fermented Cyclopia subternata, Cyclopia intermedia, Cyclopia genistoides and Cyclopia sessiliflora was evaluated. Known compounds that were identified and quantified include mangiferin (0.1–11.8 g/100 g), isomangiferin (0.1–3.2 g/100 g), eriocitrin (not detected–0.4 g/100 g), hesperidin (0.2–1.2 g/100 g) and scolymoside (not detected–1.8 g/100 g), while narirutin and luteolin were detected in most samples, but could not be quantified due to low concentrations and co-elution. An unidentified compound (traces–4.8 g hesperidin equivalents/100 g), unidentified hydroxycinnamic acid derivative (not detected–0.3 g mangiferin equivalents/100 g), unidentified flavanone (not detected–2.0 g hesperidin equivalents/100 g) and an eriodictyol-glycoside (not detected–0.5 g hesperidin equivalents/100 g) could also be quantified. Large variation was observed within a sample series of the same extract type due to the nature of the plant material. Qualitative and quantitative differences were observed between species, while “fermentation”, a high-temperature process involving non-enzymatic oxidation, decreased the content of most phenolic compounds. Results using DAD as the only detection method should be handled with care, as the tentative identification of compounds 9 and 10, based on retention time and UV–Vis spectrum, could not be confirmed using liquid chromatography–electrospray ionisation-mass spectrometry.