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51.
Severe myoclonic epilepsy (SMEI) or Dravet syndrome is caused by mutations of the SCN1A gene that encodes voltage-gated sodium channel alpha-1 subunit. Recently, we generated and characterized a knock-in (KI) mice with an SCN1A nonsense mutation that appeared in three independent SMEI patients. The SCN1A-KI mice well reproduced the SMEI disease phenotypes. Both homozygous and heterozygous knock-in mice developed epileptic seizures within the first postnatal month. In heterozygous knock-in mice, trains of evoked action potentials in inhibitory neurons exhibited pronounced spike amplitude decrement late in the burst but not in pyramidal neurons. We further showed that in wild-type mice the Nav1.1 protein is expressed dominantly in axons and moderately in somata of parbalbumin (PV) – positive inhibitory interneurons. Our immunohistochemical observations of the Nav1.1 are clearly distinct to the previous studies, and our findings has corrected the view of the Nav1.1 protein distribution. The data indicate that Nav1.1 plays critical roles in the spike output from PV interneurons and further, that the specifically altered function of these inhibitory circuits may contribute to epileptic seizures in the mice. These information should contribute to the understanding of molecular pathomechanism of SMEI and to develop its effective therapies.  相似文献   
52.
PTH has diverse effects on bone metabolism: anabolic when given intermittently, catabolic when given continuously. The cellular mechanisms underlying the varying target cell response are not clear yet. PTH induces RGS-2, a member of the Regulator of G-protein Signaling protein family, via cAMP/PKA, and inactivates PKC-mediated signaling. To investigate intracellular signaling pathways with different PTH concentration-time patterns, we treated UMR 106-01 osteoblast-like cells in a perfusion system. PTH was administered intermittently (4 min/h, 10−7 M) or continuously at an equivalent cumulative dose (6.6 × 10−9 M). cAMP was measured using radioimmunoassay, mRNA levels using real-time rtPCR and ribonuclease protection assay, and protein levels using Western immunoblotting. A single PTH pulse transiently increased cAMP levels by 2000% ± 1200%. In contrast to continuous PTH exposure, cAMP induction remained unchanged with intermittent PTH, ruling out desensitization of the PTH receptor. In continuously perfused cells, RGS-2 abundance was three to five times higher than in cells intermittently exposed to PTH for up to 12 h. MKP-1 and -3 were significantly less induced with pulsatile PTH; exposure-mode-dependent differences in MMP-13 and IGFBP-5 were small. Pulsatile but not continuous PTH administration prevents PTHrP receptor desensitization and accumulation of RGS-2 in osteoblasts, which should preserve PKC-dependent signaling.  相似文献   
53.
54.
Ganoderma sinensis has been used widely in Oriental countries for the prevention and treatment of various diseases including cancer. Previous studies have shown that the lipid extract from Ganoderma exhibits direct cytotoxicity against tumor cells. Here, it is reported that the lipid extract from germinating G. sinensis spores, at lower concentrations that have no direct tumoricidal activity, induce potent antitumor immune responses in human monocytes/macrophages. Upon stimulation with the lipid extract, monocytes/macrophages exhibited markedly increased production of proinflammatory cytokines and surface expression of costimulatory molecules. Conditioned medium from stimulated cells effectively suppressed the growth of tumor cells. Apparently, the lipid extract triggered macrophage activation via a mechanism different from that associated with LPS. Moreover, it was observed that the lipid extract could partially re‐establish the antitumor activity of the immunosuppressive tumor‐associated macrophages. These results indicated that in addition to its direct tumoricidal activity, the lipid extract from G. sinensis spores could exert antitumor activity by stimulating the activation of human monocytes/macrophages. Copyright © 2008 John Wiley & Sons, Ltd.  相似文献   
55.
Aim and methods  Nutrition, unhealthy lifestyles and cancer appear to be strictly related, but few authors have analysed the interest in dietary information of cancer patients and their families. This survey was conducted in the Veneto area (Italy) to investigate the concern of cancer patients and their family members about diet as a health tool before and after diagnosis of cancer. Results  Seven hundred and four questionnaires were collected: 380 from cancer patients and 324 from family members of cancer subjects. Breast cancer (BC) was the most frequent disease for patients (61.8%) as well as families (26.5%). Generally, the importance of having precise diet information after diagnosis is recognised by 40.3% of patients, with significant differences between the various types of cancer: gastric and colon/rectum cancer (GCC) patients were more concerned than BC women about precise information concerning a diet to follow immediately after diagnosis (p = 0.000, ODs = 3.10, CI 1.68–5.71) or during treatments (p = 0.001, ODs = 2.67, CI 1.46–4.89). The nutritional information is supplied to patients in 34% of cases and to relatives in 30.3%, often from non-medical sources. In total healthcare workers (family doctor, oncologist, surgeon, dietician) represented the exclusive source of dietary information for 24.9% of patients and 22.9% of family members. Diet after diagnosis changes in 69.1% of GCC patients and in 39.2% of BC women. Relatives, particularly women, report difficulties preparing patients’ meals in 30.7% of cases, changes in the eating habits of the entire family in 29.9% and discontent connected with patients diet in 13.9%. The concern about proper nutrition after diagnosis increases more in GCC subjects (p < 0.025) when compared to BC subjects and in patients with more recent diagnosis (p < 0.041) when compared with patients with diagnosis >5 years ago, while in family members the interest in diet after diagnosis increases more in women than in men (p < 0.030) without other differences regarding the degree of relationship, type of cancer or diagnosis time. Relatives (92.7%) have more interest in nutritional education than patients (74.9%). Cancer patients <65 years were more interested in educational initiatives concerning nutrition (p = 0.000, ODs = 4.46, CI 2.6–7.4) than older patients (>65 years) and female subjects were more concerned than male patients (p = 0.008, ODs = 2.11, CI 1.2–3.6). Conclusions  The interest in the dietary knowledge and in educational initiatives concerning nutrition is high in cancer patients and their relatives, although it decreases with the age. The poor attention paid to nutrition of cancer patients by various healthcare workers deserves consideration, since the psychophysical wellbeing and perhaps also survival of cancer patients can be improved by correct dietary management, as well as, naturally, by the principal treatments themselves.  相似文献   
56.
Atopic eczema/dermatitis syndrome (AEDS) commonly often arises during early infancy. In several intervention studies a beneficial influence on AEDS course of certain intestinal bacteria, administered as 'probiotics', has been described. To evaluate the possible role of the natural intestinal microflora in children with allergic eczema/dermatitis syndrome regarding immediate type hypersensitivity to food allergens, children with food allergy (AAEDS, n = 68) have been compared with children without detectable food allergy (NAEDS, n = 25). All children (n = 93) in preschool age, mean age of 2.6 (+/-1.8) years, diagnosed with AEDS who were treated as inpatients in 2003 in a dermatological hospital were included. The correlation between fecal microflora, parasites and specific immunoglobulin E (IgE) antibodies against common food allergens was analyzed. A similar composition of intestinal microflora in children with AAEDS and NAAEDS was found. The food allergens that were most frequently detected were egg white, cow milk, casein, peanut and hazelnut. Furthermore, a significant association between IgE sensitization against important food allergens and components of the fecal microflora could not be demonstrated. With aging changes occur in the intestinal microbiota [Proteus/Klebsiella and age (rho = -0.607) and Enterococcus and age (rho = -0.428)]. In two subjects of the AAEDS group Blastocystis hominis was found. The composition of natural intestinal microflora in children with AAEDS and NAAEDS was similar. Hence, there is no evidence of a role of the intestinal microflora with regard to the development of infant (food) allergy in children with AEDS. The possible consequences for allergic diseases later in life require further investigation.  相似文献   
57.
The mechanism of release from sustained-release adinazolam mesylate tablets was assessed by the Higuchi equation and by analysis of drug release profiles through 60% released using the Peppas equation. Computed values of the diffusional exponent, n, ranged from 0.59 to 0.66. Values of n in this range are consistent with a mixed mechanism of release, with diffusion of drug through the hydrated polymer matrix and relaxation of this matrix being the principal processes controlling release. The rate of in vitro drug release was increased for half tablets relative to whole tablets and is attributed to an increase in the surface to volume ratio of half tablets of about 16%. This increase in surface-to-volume ratio of half tablets was reflected by an increase in the constant, k, from the Peppas equation of 20–23% and by an increase in the slope of Higuchi plots of 12–18% for four lots of tablets. In vivo/in vitro relationships from two bioavailability studies were thoroughly evaluated. Using either a linear or a quadratic relationship, an in vivo/in vitro correlation exists for sustained-release adinazolam mesylate tablets.  相似文献   
58.
59.
目的 探讨Ⅴ型斜视伴原发性下斜肌功能过强的治疗效果。方法根据手术方式将49例Ⅴ型斜视伴下斜肌功能过强惠者分为四组,分别采用水平肌加强减弱术不联合下斜肌切断减弱术(Ⅰ组)、联合单侧下斜肌切断减弱术(Ⅱ组)、联合双侧下斜肌对等切断减弱术(Ⅲ组)及联合双侧下斜肌不对等切断并部分切除减弱术(Ⅳ组)治疗Ⅴ型斜视。结果Ⅴ型斜视伴原发性下斜肌功能过强采用四种方式治疗后,眼位正位,下斜肌功能亢进改善+~++,双侧下斜肌功能对等,术前术后原在位度数和上下注视25。斜视角之差的差异有非常显著性(P〈0.001)。结论根据单侧或双侧下斜肌功能过强的具体情况来选择不同的手术方式治疗Ⅴ型斜视伴原发性下斜肌功能过强,眼位矫正满意,同时手术方式简单、安全有效。  相似文献   
60.
In primary visual cortex of hooded rats, pyramidal cells in layer V may be classified as long, medium, or short, on the basis of the layer in which the apical dendrite terminates. The present study determines which of these types of pyramidal cells project to the superior colliculus. Two different strategies were used to label corticotectal cells with horseradish peroxidase (HRP). In the first set of experiments, a large number of corticotectal cells were labeled by retrograde transport following injection of HRP into the superior colliculus. In the second set of experiments, single unit recording was used to identify corticotectal cells physiologically by antidromic activation from the superior colliculus. These cells were then impaled and labeled by intracellular iontophoresis of HRP. The results from both techniques suggest that only long pyramidal cells send an axon to the superior colliculus. These cells are distinguished by an apical dendrite that extends into layer I. We conclude that in hooded rats corticotectal cells in primary visual cortex are the long pyramids in layer V.  相似文献   
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