新化合物 A-失碳-17β-羟基-17α-乙炔基-Δ3(5),9(10)-雌甾二烯-2-酮的合成

报道新化合物A-失碳-17β-羟基-17α-乙炔基-Δ^3(5),9(10)-雌甾二烯-2-酮2的合成。文中探讨了用炔钾粗品对A-失碳-Δ^3(5),9(10)-雌甾二烯-2，17-二酮１和Ａ-失碳-６β，１９-环氧-Δ³-雄甾-2，17-二酮3的选择性炔化，分别得标题化合物2（44%）及Ａ-失碳-17β-羟基-17α-乙炔基-６β，１９-环氧-Δ³雄甾-2-酮４（６５％），４经还原性破开环氧、去羟甲基和去醋酰氧基合成了标题化合物２。四步总收率为３４％。     

Acute Immobilization Stress and Intraventricular Injection of CRF Suppress Naloxone-Induced LH Release in Ovariectomized Estrogen-Primed Rats

The present study was undertaken to evaluate the role and possible interaction of the endogenous opioid peptide (EOP) and corticotropin-releasing factor (CRF) in the acute stress-induced suppression of gonadotropin secretion in ovariectomized estrogen-primed rats. An intravenous (i.v.) injection of naloxone (10 or 20  mg/kg), an EOP antagonist, significantly elevated serum luteinizing hormone (LH) levels within 10  min in non-stressed animals. The naloxone-induced LH release was completely eliminated when tested 30  min after the onset of acute immobilization. In a subsequent study, it was found that suppression of the naloxone-induced LH release occurred as early as 5  min after the stress onset, and was still evident 60  min after the end of a 30-min period of immobilization. The effect of naloxone was restored 3  h after liberation of the animal from the 30-min immobilization. An intraventricular (i.c.v.) injection of CRF (1 or 5  μg) also significantly suppressed, in a dose-related manner, the effect of a subsequent i.v. injection of naloxone. However, an i.c.v. injection of α -helical CRF(9-41) (25 or 50  μg), a CRF antagonist, prior to immobilization, could not interfere with the suppressive effect of stress on naloxone-induced LH release. These results suggest that both acute immobilization stress and CRF can inhibit the LH secretory activity without mediation by EOP neurons. However, the stress-related suppression may involve non-CRF mechanism(s).     

Gestion des risques et choix de maintenance à l'hôpitalRisks management and maintenance choices at the hospital

Regulations evolve and risks management becomes one of the biomedical engineers' preoccupations. Thus, risks are various, and consequently it is difficult to identify, to manage and to bring them under control. Furthermore, regulations exist for sectors like healthcare technology monitoring, but it is not the same thing for instance for the risks linked to the maintenance. Thus regulation in the sector of maintenance evolves and the decree of the 1^st July law of health safety is going to modify the biomedical environment. The goal of this work is to study the tools and the methods of risks management that have been used for several years in the industrial field and to use them for some biomedical equipment like monitors or IV pumps. These methods adapted to these equipment will allow us to determine some appropriate rules of maintenance.     

9-顺式维甲酸体外诱导神经母细胞瘤细胞分化的研究

目的：为设计维甲酸治疗神经母细胞瘤可能的有效方案，本文对9-顺式维甲酸（9-cis retinoic acid,9-cisRA)体外诱导分化神经母细胞瘤细胞（SK-N-SH）作用进行了研究。方法：SK-N-SH细胞经9-cisRA处理后，采用相差显微镜，神经纤维银染法，透射电镜观察等手段。观察9-cisRA对细胞生长的影响。结果：9-cisRA作用SK-N-SH细胞7d后，细胞形态发生变化；12d时出现神经原性表型，多个细胞形成“神经节”，节间形成粗而长的类神经纤维；尼氏小体和银染法亦证明细胞产生显著分化，透射电镜观察结果表明，9-cisRA对该细胞有分化作用。却无明显凋亡诱导作用。结论：9-cisRA对神经母细胞瘤细胞体外能产生明显诱导分化作用。     

Are hospitals prepared to support newborn survival? – an evaluation of eight first‐referral level hospitals in Kenya*

Objective To assess the availability of resources that support the provision of basic neonatal care in eight first‐referral level (district) hospitals in Kenya. Methods We selected two hospitals each from four of Kenya’s eight provinces with the aim of representing the diversity of this part of the health system in Kenya. We created a checklist of 53 indicator items necessary for providing essential basic care to newborns and assessed their availability at each of the eight hospitals by direct observation, and then compared our observations with the opinions of health workers providing care to newborns on recent availability for some items, using a self‐administered structured questionnaire. Results The hospitals surveyed were often unable to maintain a safe hygienic environment for patients and health care workers; staffing was insufficient and sometimes poorly organised to support the provision of care; some key equipment, laboratory tests, drugs and consumables were not available while patient management guidelines were missing in all sites. Conclusion Hospitals appear relatively poorly prepared to fill their proposed role in ensuring newborn survival. More effective interventions are needed to improve them to meet the special needs of this at‐risk group.     

Impact of type 2 diabetes mellitus on diffuse inflammatory activation of de novo atheromatous lesions: Implications for systemic inflammation

AimsLocal coronary and systemic inflammation is pronounced in patients with diabetes mellitus (DM). Intracoronary thermography detects local inflammation and C-reactive protein (CRP) is a marker of systemic inflammation. We investigated whether or not, in patients with DM, thermal heterogeneity of culprit lesions (CLs) correlates with that of non-culprit lesions (NCLs) and with systemic inflammation.MethodsWe included DM patients who had two angiographically significant lesions and were undergoing percutaneous coronary intervention. We measured the temperature difference (ΔT) between the lesion and proximal vessel wall.ResultsWe included 104 (n = 208 lesions) patients: 32 (n = 64 lesions) had DM and 72 (n = 144 lesions) were non-DM (control group). ΔT was increased in DM in both CLs and NCLs (CLs: DM = 0.12 ± 0.06 °C; no DM = 0.06 ± 0.04 °C; P < 0.01 versus NCLs: DM = 0.13 ± 0.08 °C versus no DM = 0.06 ± 0.05 °C; P < 0.01). Patients with DM had similar ΔT in CLs and NCLs (P = 0.49). A linear correlation was detected between heat production in all lesions and CRP (R = 0.45; P < 0.01), which was attributed to the correlation of ΔT in lesions of patients with DM and CRP (R = 0.32; P < 0.01). In lesions of patients with low CRP, a greater rate of discrepancy was found, as 100% of lesions in patients with DM versus 66.1% of lesions of patients without DM had a high ΔT in one or both lesions (P < 0.01).ConclusionIn patients with DM, local inflammatory activation is diffuse and correlates with systemic inflammation. However, low systemic inflammatory activation does not always predict an increase in local thermal heterogeneity.     

How far do patients with sensory ataxia benefit from so-called “proprioceptive rehabilitation”?

A rehabilitation program including foot sensory stimulation, balance and gait training with limited vision was performed in 24 patients with clinically defined sensory ataxia. There were 15 patients with bilateral somatosensory loss related to chronic neuropathy and nine patients with unilateral loss-related to multiple sclerosis. After training, balance control assessed using the Berg Balance Test improved similarly in both groups, and Romberg's sign disappeared in some patients, suggesting an improvement in dynamic balance and in the proprioceptive contribution. Conversely, balance assessed on a static force platform remained similar in the open-eyes condition and improved in the closed-eyes condition only in patients with unilateral sensory loss. These results show that ataxic patients can improve their balance with better results in dynamic conditions and that the relative contribution of proprioceptive and visual inputs may depend on the extent of somatosensory loss.     

Open, Double-Blind and Long-Term Study of Vigabatrin in Chronic Epilepsy

We performed an open, double-blind, and long-term study of vigabatrin (gamma-vinyl-GABA, GVG) in patients with treatment-resistant epilepsy who were receiving only one or at most two standard antiepileptic drugs (AEDs). The novel design included a parallel, double-blind, placebo-controlled phase that minimized the number of patients receiving placebo and allowed determination of the optimum dose of GVG for each patient before initiation of the double-blind phase. The study was divided into four phases. The first phase was a 6-week period of baseline observation. In the second phase, GVG was added openly to previous AEDs for 8 weeks. During the first 2 weeks of this phase, the dose of GVG was increased weekly and then, in the absence of adverse effects, was held constant for the next 6 weeks. At the end of this open phase, seizure frequency during the 6 weeks of constant treatment was compared with the baseline seizure frequency for each patient. Patients who experienced reduction greater than 50% in the frequency of any seizure type during the open phase were defined as responders. These responders were then entered into the third and double-blind phase, in which they were randomly allocated wither to continue active GVG treatment or placebo for 8 weeks. Thirty-three patients entered the study; 31 of 33 patients completed the initial open phase. Twenty patients achieved a reduction greater than or equal to 50% in the frequency of one or more seizure types and were eligible for the double-blind phase; 10 were randomized to continue GVG and 10 were randomized to placebo.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preparation of protected peptidyl thioester intermediates for native chemical ligation by Nα‐9‐fluorenylmethoxycarbonyl (Fmoc) chemistry: considerations of side‐chain and backbone anchoring strategies,and compatible protection for N‐terminal cysteine*,†

Abstract: Native chemical ligation has proven to be a powerful method for the synthesis of small proteins and the semisynthesis of larger ones. The essential synthetic intermediates, which are C‐terminal peptide thioesters, cannot survive the repetitive piperidine deprotection steps of N^α‐9‐fluorenylmethoxycarbonyl (Fmoc) chemistry. Therefore, peptide scientists who prefer to not use N^α‐t‐butyloxycarbonyl (Boc) chemistry need to adopt more esoteric strategies and tactics in order to integrate ligation approaches with Fmoc chemistry. In the present work, side‐chain and backbone anchoring strategies have been used to prepare the required suitably (partially) protected and/or activated peptide intermediates spanning the length of bovine pancreatic trypsin inhibitor (BPTI). Three separate strategies for managing the critical N‐terminal cysteine residue have been developed: (i) incorporation of N^α‐9‐fluorenylmethoxycarbonyl‐S‐(N‐methyl‐N‐phenylcarbamoyl)sulfenylcysteine [Fmoc‐Cys(Snm)‐OH], allowing creation of an otherwise fully protected resin‐bound intermediate with N‐terminal free Cys; (ii) incorporation of N^α‐9‐fluorenylmethoxycarbonyl‐S‐triphenylmethylcysteine [Fmoc‐Cys(Trt)‐OH], generating a stable Fmoc‐Cys(H)‐peptide upon acidolytic cleavage; and (iii) incorporation of N^α‐t‐butyloxycarbonyl‐S‐fluorenylmethylcysteine [Boc‐Cys(Fm)‐OH], generating a stable H‐Cys(Fm)‐peptide upon cleavage. In separate stages of these strategies, thioesters are established at the C‐termini by selective deprotection and coupling steps carried out while peptides remain bound to the supports. Pilot native chemical ligations were pursued directly on‐resin, as well as in solution after cleavage/purification.     

胃癌组织中CA19-9的表达研究

目的 研究肿瘤相关抗原CA19－9在胃癌组织中的表达情况。方法 采用免疫组织化学方法对30例胃癌、癌旁组织、正常胃粘膜和30例胃溃疡组织中的CA19－9的表达情况进行了检测。结果 30例胃癌CA19－9阳性表达23例（76.7%,23/30)。其中胞浆和胞膜均阳性的16例（69.6%,16/23)，而仅胞膜阳性5例（21.7%,5/23)。30例癌旁组织CA19－9阳性表达1例（3.3%,1/30)且为胞膜阳性。正常胃粘膜和胃溃疡组织中CA19－9表达均为阴性。在10例高分化腺癌组织中阳性4例，17例低分化腺癌组织中阳性16例，3例粘液癌全为阳性。结论 胃组织中CA19－9的表达可能成为胃癌的肿瘤标志之一，尤其适用于低分化腺癌和粘液癌，而对高分化腺癌不适合。