The polyhydroxylated derivatives of 6-keto,7-dehydrocholesterol (ecdysone, ecdysteroids, Ecd) are natural compounds widely distributed in plants. They exhibit strong anabolic, vitamin D-like, pharmacological effects in vertebrate animals and in the human body. In the larval stages of insects, injections of pure Ecd cause serious pathophysiological, "hyperecdysonic" syndromes associated with neuromuscular paralysis, premature cuticular apolysis and complete inhibition of ecdysis. Ecds do not penetrate insect cuticle. For this reason, all previous attempts to induce ecdysone responses by topical applications of Ecd failed. In this work, we tried to induce the topical effects of Ecd by preparation of more lipophilic complexes, with 2 or 4 molecules of 20-hydroxyecdysone (E20) attached to a relatively large nucleus of the porphyrin. The resulting porphyrin-E20 complexes (ecdysogens) have been subjected to standardised assays for ecdysone activity in the ligatured larvae ("dauerlarvae") of the greater waxmoth (Galleria mellonella). Similarly like the free E20 alone, porphyrin-E20 complexes had no effect when applied on the body surface or administered in the larval diet. When injected, however, they exhibited delayed effects, but the adverse ("hyperecdysonic") pathophysiological syndromes were reduced or abolished. It is concluded, therefore, that the replacement of pathophysiological, precocious or "hyperecdysonic" moults by the larval-pupal transformation, was due to successive metabolic liberation of the biologically active, free E20 from the porphyrin-E20 complex. The biological status of Ecd does not agree with their definition as the prothoracic gland (PG) hormone of insects, nor with the assumptions about a growth hormone of plants. A possibility that the most important status of Ecd may depend on the pharmacological properties of a sterolic D6 vitamin has been discussed.

2007-01-01·International Journal of Psychiatry in Clinical Practice4区 · 医学

The sufficiency of the HAM-D₆as an outcome instrument in the acute therapy of antidepressants in the outpatient setting

4区 · 医学

Article

作者: R Dal-Re ; A Luque ; A Bulbena ; J Bobes ; J Ballesteros ; P Bech ; N Ibarra

Objective. To re-analyse the Spanish outpatient study on the various versions of the Hamilton Depression Scale (HAM-D) by using item-response theory models for measuring unidimensionality. Methods. The Mokken analysis, based on the coefficient of homogeneity, was used. A coefficient of 0.40 or higher was accepted for unidimensionality. The three HAM-D versions were compared: HAM-D6 (core items of depression), HAM-D17 and HAM-D21. Results. In total, 113 of the 116 patients included in the study completed the planned treatment period of 6 weeks. As the Mokken analysis depends as much on the sample of patients under examination (dispersion of scores on the item) as on the scale itself, the endpoint was used. For HAM-D6, but not for HAM-D17 or HAM-D21, the coefficient of homogeneity was acceptable (0.44). Conclusion. The HAM-D6 is a valid version of the Hamilton Scale to be recommended for monitoring depressed patients in antidepressant therapy in the outpatient setting.

Pathogens

Identification of an IGHV3-53-Encoded RBD-Targeting Cross-Neutralizing Antibody from an Early COVID-19 Convalescent

Article

作者: Ren, Li ; Hu, Caiqin ; Su, Junwei ; Liang, Hao ; Wang, Shuo ; Hu, Yuanyuan ; Li, Dan ; Hao, Yanling ; Wang, Zheng ; Shao, Yiming ; Liu, Ying ; Zhu, Biao

Since November 2021, Omicron has emerged as the dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, and its sublineages continue to appear one after another, significantly reducing the effectiveness of existing therapeutic neutralizing antibodies (NAbs). It is urgent to develop effective NAbs against circulating Omicron variants. Here, we isolated receptor binding domain (RBD)-specific single memory B cells via flow cytometry from a COVID-19 convalescent. The antibody variable region genes of the heavy chain (VHs) and light chain (VLs) were amplified and cloned into expression vectors. After antibody expression, ELISA screening and neutralizing activity detection, we obtained an IGHV3-53-encoded RBD-targeting cross-neutralizing antibody D6, whose VL originated from the IGKV1-9*01 germlines. D6 could potently neutralize circulating Omicron variants (BA.1, BA.2, BA.4/5 and BF.7), with IC50 values of less than 0.04 μg/mL, and the neutralizing ability against XBB was reduced but still effective. The KD values of D6 binding with RBD of the prototype and BA.1 were both less than 1.0 × 10−12 M. The protein structure of the D6-RBD model indicates that D6 interacts with the RBD external subdomain and belongs to the RBD-1 community. The sufficient contact and deep interaction of D6 HCDR3 and LCDR3 with RBD may be the crucial reason for its cross-neutralizing activity. The sorting and analysis of mAb D6 will provide important information for the development of anti-COVID-19 reagents.

100 项与 Deudextromethorphan Hydrobromide 相关的药物交易

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