Influence of Rh phenotype on the antigen density of C, c, and D: flow cytometric study using a frozen standard red cell

BACKGROUND: Flow cytometry is increasingly being used for the comparison of antigen density. Indirect immune fluorescence is more sensitive than direct immune fluorescence and thus allows the study of red cells (RBCs) with a weak D antigen. STUDY DESIGN AND METHODS: In indirect immune fluorescence, when the fluorescence is standardized by the use of aliquoted frozen standard RBCs, the coefficient of variation in fluorescence intensity was less than 5 percent, which allows accurate determination of minor variations of Rh antigen density. RESULTS: For D antigen, the well-known suppressive effect of C, and the low antigen density of the weak D phenotype, was demonstrated. Use of epitope-specific monoclonal antibodies yielded similar results and allowed the identification of a D category IV heterozygote; the relative antigen density measured with a monoclonal antibody that reacted with D(IV) was twice that measured with a monoclonal antibody that did not react with D(IV). RBCs from C and c homozygotes had significantly more antigen than those from heterozygotes. There was significant variation in antigen density, depending on Rh phenotype: for example, D+ RBCs had less C antigen than D- RBCs, and Rh:1,2,-3,4,5 (CcDee) RBCs had more c antigen than Rh:1,2,3,4,5 (CcDEe) RBCs. There was no difference in D, C, and c antigen density in neonatal and adult RBCs. CONCLUSION: Flow cytometry is an excellent tool for the demonstration of minor differences in antigen density.     

尼群地平片剂生物利用度的研究

为提高国产尼群地平片剂的生物利用度,采用球磨混合粉碎法工艺进行处方设计,试制出新处方片剂,与西德Bayer公司片剂进行了体外溶出、体内生物利用度的比较。体内血浆药浓用GC-MS法测定,体内数据按零级溶出、一级吸收口服单室模型,经计算机用Gauss-Newton-Damping法处理求得药动学参数。本文研制的尼群地平新处方片剂生物利用度已超过西德Bayer公司片剂。     

美托洛尔酒石酸盐胃内滞留漂浮型控释片的制备及药代动力学研究

本文根据水动力学平衡药物控释系统的设计原理制备了美托洛尔胃内滞留漂浮型控释片剂(简称M-HBS)。实验表明,本品的体外溶出符合一级动力学过程(K′r=0.1651 h^-1);贮存期为两年;人体胃内γ-闪烁照相结果表明,本品在胃内滞留时间(5～6 h)明显比普通片剂(1.0～1.5 h)长;体内动力学过程符合表观一级吸收与一级消除的单室模型;ⅳ美托洛尔体内为双室模型;体内数据经NONLIN计算机程序处理,求得各项参数:Ka=0.1944 h^-1,K=0.1867 h^-1,Vd=2.813,t_max=5.247 h,C_max=125.1 ng/ml。本品的体内外数据具有显著的相关性(P<0.01)。     

Investigational small molecules in phase II clinical trials for the treatment of epilepsy

ABSTRACT

Introduction: Epilepsy is a neurological disorder that significantly impacts the quality of life of affected persons. Despite advances in research, nearly a third of patients have refractory or pharmacoresistant epilepsy. Even though numerous antiepileptic drugs (AEDs) have been approved over the past decade, there are no agents that halt the development of epilepsy. Thus, new and improved AEDs to prevent these conditions are necessary.

Areas covered: We highlight recent advances in new and innovative drugs for epilepsy disorders. We review three small molecule drugs in phase II clinical trials: Cannabidivarin, BGG492 (Selurampanel) and Ganaloxone.

Expert opinion: The full potential of Cannabidivarin will be realized by testing in other types of treatment-resistant seizures; if they are beneficial, larger phase III clinical trials would probably be undertaken in the same patient population. About BGG492, the challenge will be to find ‘superselective’ AMPAR antagonists targeting only calcium-permeable receptors, with specific mechanisms, that may be attractive partners for drugs in polytherapy. Moreover, there is anew interest surrounding Ganaloxone because of a new submicron formulation that improves its absorption and pharmacokinetic profile, but new studies are necessary before progressing. Further clinical innovations will define the future for these small molecule-type drugs in epilepsy therapeutics.     

A randomized trial comparing cadexomer iodine and standard treatment in the out-patient management of chronic venous ulcers

Ninety-three patients with treatment-resistant venous ulcers were included in a multicentre randomized trial to compare cadexomer iodine and the standard treatment used in each centre combined with compression bandages, in healing venous ulcers. The mean duration of ulcers before the trial was more than 2 years. With standard treatment the mean ulcer size increased slightly during the 6-week trial whereas with cadexomer iodine the ulcer size was significantly reduced. Cadexomer iodine was more effective than standard treatment for reduction of pain, removal of pus and debris, removal of exudate, stimulation of granulation and reduction of surrounding erythema. Bacterial infection of ulcers increased or did not change during treatment with the standard therapy whereas cadexomer iodine significantly reduced infection with Staphylococcus aureus, Pseudomonas aeruginosa and other pathogenic organisms. A correlation was seen between the time taken to reduce or eliminate infection with Staphylococcus aureus and rate of ulcer healing. Four patients complained of transient pain in the ulcer after application of the cadexomer iodine. It is concluded that cadexomer iodine increased the rate of healing of infected chronic venous ulcers.     

Specificity of Receptors for IgG on Human Lymphocyte-Like Cells

Some human lymphocyte-like cells (EA-RFC) have receptors for IgG demonstrable by their ability to form rosettes with human Rh-positive O erythrocytes sensitized with anti-CD isoantibodies (Ripley). The specificity of these receptors for the various Ig classes, IgG subclasses, and fragments of the IgG molecule was determined by studying the inhibitory capacity of the corresponding immunoglobulins in the rosette assay. The receptors showed specificity only for IgG among the Ig classes and about equal affinity for IgG1 and IgG3, but only weak binding of IgG2 and IgG4 was obtained. Whereas no inhibition was obtained with Fab and F(ab')₂ fragments prepared from IgG, the Fc fragment showed strong inhibitory capacity, which was even surpassed by the IgG3 Fch fragment, containing an extension from the N-terminal part of Fc. The inhibitory capacity of the Fc and Fch fragments was considerably reduced by partial reduction and alkylation. The pFc' fragment of IgG, which corresponds to the C_γ3 region, did not inhibit rosette formation. These data indicate that mainly the C_γ2 region is involved in the binding of IgG to EA-RFC. Inhibition studies did not show any differences in the relative inhibitory capacity of monomerie, dimeric, or highly polymerized (heat-aggregated) IgG. However, antibodies of rabbit origin complexed with antigen (ferritin) gave stronger inhibition than the corresponding native Ig.     

Structural analysis of fMRI data: a surface-based framework for multi-subject studies

We present a method for fMRI data group analysis that makes the link between two distinct frameworks: surface-based techniques, which process data in the domain defined by the surface of the cortex, and structural techniques, which use object-based representations of the data as opposed to voxel-based ones. This work is a natural surface-based extension of the volume-based structural approach presented in a previous paper. A multi-scale surface-based representation of individual activation maps is first computed for each subject. Then the inter-subject matching and the activation detection decision are performed jointly by optimization of a Markovian model. Finally, a significance measure is computed in a non-parametric way for the results, in order to assess their relevance and control the risk of type I error. The method is applied on simulated and real data and the results are compared to those produced by standard analyses. The surface-based structural analysis is shown to be particularly robust to inter-subject spatial variability and to produce relevant results with good specificity and sensitivity. We also demonstrate the advantages of the surface-based approach by comparing with the results of a 3D structural analysis.