Relative bioavailability of four controlled-release nifedipine products

Four controlled-release nifedipine products were investigated in two clinical studies. In study 1, 22 healthy male volunteers took part in an open, multiple-dose, randomized, crossover study to determine the relative bioavailablity of two 10 mg controlled-release nifedipine tablet (Adalat® Retard, Bayer), administered 12 hourly, and one 20 mg controlled-release nifedipine tablet (Adalat® Retard, Bayer) administered 12 hourly. In study 2, 24 healthy male volunteers took part in an open, multiple-dose, randomized, three-period, crossover study to determine the relative bioavailability of (i) two 30 mg nifedipine gastro-intestinal therapeutic system (GITS) tablets (Adalat® XL, Bayer) administered once daily; (ii) one 60 mg nifedipine GITS tablet (Adalat® XL, Bayer) administered once daily; and (iii) one 20 mg plus one 10 mg nifedipine controlled-release tablet (Adalat® Retard, Bayer), administered 12 hourly. In both studies detailed pharmacokinetic data, in particular with respect to the controlled-release characteristics of the different formulations, were collected. Results of both studies indicate that all nifedipine products investigated are bioequivalent with respect to the extent of absorption of nifedipine. The nifedipine GITS products (Adalat® XL) have better controlled-release properties than the Adalat® Retard product, and are suitable for once-a-day administration.     

努力推进军队卫生系统的计算机应用

系统地介绍了军队卫生系统计算机应用的概况，总结了军队卫生系统自动化建设的主要经验，并提出了加强军队卫生系统计算机应用的设想。     

Flunarizine induces a transient loss of tyrosine hydroxylase immunoreactivity in nigrostriatal neurons

Neurotoxic effects of flunarizine (Fz), a selective calcium channel blocker, on the nigrostriatal dopamine system was investigated. Systemic injections of Fz to mice resulted in a transient loss of tyrosine hydroxylase (TH) immunoreactive nigrostriatal neurons without cell loss. TH immunoreactivity in these neurons was greatly reduced as rapidly as one day after drug administration (regardless of dosage used) and thereafter recovered in both dose- and time-dependent manners. Such a novel neurotoxic action of Fz may constitute a morphological substrate for reversible drug-induced parkinsonian signs described in recent clinical case reports.     

小鼠胸腺和脾脏细胞的体外转化培养

建立了小鼠脾脏、胸腺细胞体外转化微量培养系统,确定了最佳实验条件.点蜡法充CO_2,简便易行,效果好.RPMI-1640培养基内补充胎牛血清,其浓度确定为在脾细胞培养为10%,在胸腺细胞培养为20%.脾细胞培养最适细胞密度为2～5×10~6/ml,Con A最适量为2～4μg/培养;胸腺细胞培养细胞最适密度为1×10~7/ml,Con A最适量为2～4μg/培养.两种已知免疫活性的药物在脾细胞培养体系有明确肯定的反应.     

Effect of KB-2796, a new diphenylpiperazine Ca antagonist, on voltage-dependent Ca currents and oxidative metabolism in dissociated mammalian CNS neurons

The effects of KB-2796, 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine-2HCl, on the low- and high-voltage activated Ca²⁺ currents (LVA and HVA I_Ca, respectively) and on oxidative metabolism were studied in neurons freshly dissociated from rat brain. KB-2796 reduced the peak amplitude of LVA I_Ca in a concentration-dependent manner with a threshold concentration of 10⁻⁷ M when the LVA I_Ca was elicited every 30 s in the external solution with 10 mM Ca²⁺. The concentration for half-maximum inhibition (IC₅₀) was 1.9 × 10⁻⁶M. At 10⁻⁵ M or more of KB-2796, a complete suppression of the LVA I_Ca was observed in the majority of neurons tested. There was no apparent effect on the current-voltage (I-V) relationship and the current kinetics. KB-2796 delayed the reactivation and enhanced the inactivation of the Ca²⁺ channel for LVA I_Ca voltage- and time-dependently, suggesting that KB-2796 preferentially binds to the inactivated Ca²⁺ channel. KB-2796 at a concentration of3.0 × 10⁻⁶M also decreased the peak amplitude of the HVA I_Ca without shifting the I-V relationship. In addition, KB-2796 reduced the oxidative metabolism (the formation of reactive oxygen species) of the neuron in a concentration-dependent manner with a threshold concentration of3 × 10⁻⁶M. It is suggested that the inhibitory action of KB-2796 on the neuronal Ca²⁺ influx and the oxidative metabolism, in combination with a cerebral vasodilatory action, may reduce ischemic brain damage.     

Moving beyond empiric continuous positive airway pressure (CPAP) trials for central sleep apnea: a multi-modality titration study

There is no universally accepted method to determine effective therapy for central sleep apnea (CSA). Continuous positive airway pressure (CPAP) applied acutely most often does not eliminate apneas and hypopneas. We hypothesized that the application of two or more therapeutic modalities after the diagnostic phase of polysomnography, a multi-modality titration study (MMTS), would identify a successful CSA treatment more often than a standard split-night study (SNS) and obviate the need for additional polysomnograms to determine a successful therapy. We retrospectively analyzed polysomnograms of patients diagnosed with CSA at our Sleep Disorders Center. We defined a therapy trial that resulted in an apnea–hypopnea index < 10 with at least one treatment modality as a therapeutic success. One hundred fifteen patients with CSA were studied. Sixty-six patients (57.4%) underwent a SNS, and 49 patients (42.6%) underwent a MMTS. SNS yielded only 8/66 (12.1%) successes on the first night, whereas a MMTS yielded 19/49 (38.8%) successes (p = 0.001, two-tailed Fishers exact). Patients who underwent a SNS eventually had similar rate of success as patients studied with MMTS (60.6 vs 63.3%, NS), but required more testing. Adaptive servo-ventilation was the most successful modality tested, yielding 36/46 (78.3%) successes. Trials of additional modalities following a failed trial of CPAP often produce a successful option that may guide therapy in patients with CSA. This approach may lead to establishing the diagnosis and treatment plans faster, while reducing unnecessary testing.     

中心流形定理在非线性动力学系统分析和控制中的应用

本文将中心流形定理用于一类非线性动力学系统的局部定量分析和设计中,从而改进和简化了传统的分析和设计方法,弥补了线性化方法在处理这类系统方面的不足。     

The child with recurrent respiratory infections: normal or not?

Respiratory infections (RI) are one of the major complaints in children and adolescents, and represent a demanding challenge for the pediatrician. It has been estimated that at least 6% of Italian children younger than 6 yr of age present recurrent respiratory infections (RRI). Children with RRI are not affected by severe alterations of the immune system. RRI represent essentially the consequence of an increased exposure to infectious agents during the first years of life, when immune functions are still largely immature. Several social and environmental factors, such as day-care attendance, family size, air pollution, parental smoking, and home dampness, represent important risk factors for airway diseases and may contribute in various degrees to determine the incidence of RRI. The main problem for the pediatrician is to discriminate normal children with high RI frequency related to an augmented exposure to environmental risk factors from children affected by other underlying pathological conditions (immunological or not), predisposing to infectious diseases. When RRI diagnosis has been formulated, removal of environmental risk factors (i.e. precocious day-care attendance, smoking in the household) must first be suggested.     

76例轮状病毒性肠炎临床症状观察

目的 :分析 76例轮状病毒 (RV)性肠炎患者的临床症状。方法 :对 76例不同年龄组 RV肠炎患儿的临床症状进行回顾性分析。结果 :1同时出现呼吸系统症状并伴流涕、鼻塞、咳嗽、气促 59例 ;支气管炎 19例 ;肺炎 5例。 2出现抽搐7例。 3生化检查结果门冬氨酸氨基转移酶 (AST)明显增高 76例 ;肌酸激酶 (CK)增高 52例 ;丙氨酸氨基转移酶 (AL T)轻度增高 48例 ;乳酸脱氢酶 (L DH)增高 13例。 4X线胸片肺纹理增粗 8例 ;双肺斑片影 4例。 5心电图表现窦性心动过速 4例 ,T波改变 1例。结论 :RV感染可造成病毒血症 ,且可呈多系统播散 ,使机体各脏器组织损伤 ,致婴幼儿发病。故要对这一弱小群体实行早期预防保健 ,有关部门应引起重视     

Why study transport of peptides and proteins at the neurovascular interface

The blood–brain barrier (BBB) is an immense neurovascular interface. In neurodegenerative, ischemic, and traumatic disorders of the central nervous system (CNS), the BBB may hinder the delivery of many therapeutic peptides and proteins to the brain and spinal cord. Fortunately, the mistaken dogma that peptides and proteins do not cross the BBB has been corrected during the past two decades by the accumulating evidence that peptides and proteins in the periphery exert potent effects in the CNS. Not only can peptides and proteins serve as carriers for selective therapeutic agents, but they themselves may directly cross the BBB after delivery into the bloodstream. Their passage may be mediated by simple diffusion or specific transport, both of which can be affected by interactions in the blood compartment (outside the BBB) and within the endothelial cells (at the BBB level). Although the majority of current delivery strategies focuses on modification of the molecule to be delivered, understanding the mechanisms of transport will eventually facilitate regulation of the BBB directly. We review the different aspects of interactions and discuss recent advances in the cell biology of peptide/protein transport across the BBB. Better understanding of the nature and regulation of the transport systems at the BBB will provide a new direction to enhance the interactions of peripheral peptides and proteins with the CNS.