贝伐单抗联合放射方案的实验研究

Objective To evaluate the impact of the hypoxia induced by bevacizumab on the antitumor effect in combining with irradiation in CNI-H441 xenografts in mice. Methods Bevacizumab of 5 mg/kg mouse for groups of control, bevacizumab alone, irradiation alone, earlier combination (EC), and later combination (LC) were initially injected peritoneally. Single irradiation of 14 Gy (122Sc γ-ray) was given at the 4th hour for the group of irradiation alone, 24th hour for EC group, and 72nd hour for LC group after the initial injection. Tumor hypoxia, micro vessels density and permeability of tumor vasculature,pathological responses, apoptosis, and tumor growth delay curve were evaluated after using bevacizumab and/or irradiation. Results Although it was lower than the control at the 24 hr after using bevacizumab (3. 1 × 106: 6.1 × 106 ;t = - 1.73 ,P > 0. 05), the HIF-1α rapidly increased to 3 - 4 times and 2 - 3 times of the control at day 3 (7.4 × 106: 20. 4 × 106; t = 2. 36, P < 0. 05) and lasted until day 10, which was consistent with the changes of tumor function vessels count. The count of residual micro vessel density count in LC group was higher than that in groups of EC and irradiation at day 3 after irradiation (9. 33: 3. 17;t =- 2. 43, P < 0. 05). The apoptotic count of tumor cells was lower in LC group than that in EC group (23.33: 43.83; t= 2.54, P< 0.05, at day 3 after radiation). Tumor growth delay time of LC groupwas shorter than that of EC groups (10. 5 days vs. 23. 0 days , t = 2. 67 , P < 0. 05) . Conclusions Hypoxia level induced by bevacizumab decreases the antitumor effect in later combination of bevacizumab and irradiaion. It shows a time window that determines whether the combination of bevacizumab and irradiation will be benefit or diverse.     

Enzymatic synthesis of delta sleep-inducing peptide

The delta sleep-inducing peptide was assembled enzymatically from three tripeptide fragments. All the peptide bonds were prepared by either papain- or α-chymotrypsin-mediated synthesis. Secondary hydrolysis was suppressed by introducing Nα-protected amino acid or peptide esters as carboxyl components and using an alkaline pH. The protected nonapeptide was oxidized with ferric chloride to deprotect the C-terminal phenylhydrazide and then hydrogenated. The homogeneous peptide was obtained by reversed phase high-performance liquid chromatography. Comparison of enzymatic and chemical preparations showed no obvious differences.     

Contribution of Cytochrome P450 3A Pathway to Bromocriptine Metabolism and Effects of Ferrous Iron and Hypoxia-re-oxygenation on its Elimination in the Perfused Rat Liver

The contribution of the cytochrome P450 3A pathway to bromocriptine metabolism, and the effects of ferrous iron and hypoxia-re-oxygenation on its elimination, were evaluated with the perfused rat liver. Outflow profiles of bromocriptine after bolus administration were estimated by moment analysis and dispersion model analysis. Kinetic parameters were not significantly changed by troleandomycin, a P450 3A inhibitor. The inhibition of bromocriptine metabolism by troleandomycin was 5.7 ± 2.4%. These findings indicate that cytochrome P450 3A does not play an important role in bromocriptine elimination with the perfused rat liver. Elimination rate constant (k_e) values were significantly increased by ferrous iron perfusion or hypoxia-re-oxygenation. Free-radical generation can, therefore, affect bromocriptine elimination. Our observations suggest that bromocriptine might be eliminated by scavenging of free radicals in the liver.     

Longitudinal study of the mental health of caregivers caring for elderly patients with dementia: Effect of institutional placement on mental health

Abstract  One hundred and three family caregivers of relatives with dementia were longitudinally surveyed to examine the course of caregivers' mental health after the relatives had been placed in full-time care facilities. Mental health was assessed twice, with a 6-month interval, using the Japanese version of the 60-item General Health Questionnaire. The degree of social dysfunction was significantly reduced within 6 months after placement, while the other indicators of mental health (e.g. anxiety-insomnia, depression, somatic symptom and psychiatric morbidity) were not reduced within this term. However, anxiety-insomnia and psychiatric morbidity were significantly reduced more than 6 months after placement. Analyses by caregivers' lineal relations to the relatives indicated that only daughters-in-law showed a significant decrease in anxiety-insomnia and a marginal reduction in psychiatric morbidity. This study suggests that caregivers' social dysfunction was more greatly reduced than anxiety-insomnia and psychiatric morbidity within a relatively short term after placement, and that its effects on mental health might vary with the lineal relations.     

Clinical variability of congenital myopathy with type I fiber atrophy: A long-term observation of three cases

The variable clinical courses of three cases of congenital fiber type disproportion (CFTD) over a period of 10 years are presented. All showed improvement in early childhood, but subsequently, varying degrees of deterioration were noted: specifically, marked deterioration in case 2 and decreased muscle strength in case 3. Maximal motor function levels were attained differently among the cases. Histological findings included type 1 fiber hypotrophy and increased internal nuclei in common in all cases. Fine structural changes, such as patchy areas of myofibrillar degeneration, were noted in cases 1 and 2 (second biopsy), and cytoplasmic bodies were seen in case 2 (second biopsy). Myotubes were noted in case 3. The degree of cyto-architectural changes did not correlate with clinical severity. The heterogeneity of CFTD is also discussed.     

Phasic brain activity related to the onset of rapid eye movements during rapid eye movement sleep: study of event‐related potentials and standardized low‐resolution brain electromagnetic tomography

The function of rapid eye movements (REMs) during REM sleep is still a matter that is open to debate. In a previous study, we found positive brain potential (P200r) time‐locked to the onset of REMs. This potential was not observed during saccades of wakefulness. In this study, we estimated the electrical generation of this potential to investigate the phasic brain activity related to REMs. Data were collected in a sleep laboratory from nine healthy university students. REMs during REM sleep were recorded during natural nocturnal sleep. Event‐related potential time‐locked to the onset of REMs were averaged. Standardized low‐resolution brain electromagnetic tomography (sLORETA) was used to identify the current sources of P200r. The results showed that P200r have neuronal generators in the left premotor area, left primary motor and sensory cortices, left inferior parietal lobule and bilateral occipital areas (precuneus, cuneus and lingual gyrus). All these areas are known to contribute to visuomotor processing. These phasic brain activities might play a key role in explaining the function of REMs during REM sleep.