Promoting absorption of drugs in humans using medium-chain fatty acid-based solid dosage forms: GIPET™

One of the most important and challenging goals in drug delivery is overcoming the poor oral absorption of high-value therapeutics that include peptides. Gastrointestinal Permeation Enhancement Technology (GIPET?) attempts to address this question by safely delivering drugs across the small intestine in therapeutically relevant concentrations. GIPET is based primarily on promoting drug absorption through the use of medium-chain fatty acids, medium-chain fatty acid derivatives and microemulsion systems based on medium-chain fatty acid glycerides formulated in enteric-coated tablets or capsules. Importantly, these excipients are generally regarded as safe and the systems are formulated in such a way that there is no change in chemical composition of the active ingredient. More than 300 volunteers have been administered GIPET formulations in 16 Phase I studies of 6 separate drugs comprising both single- and repeat-dosing regimes. Oral bioavailability of alendronate, desmopressin and low-molecular-weight heparin in humans was increased using GIPET formulations compared with unformulated controls. GIPET was well tolerated by human subjects. Using fluxes of markers of epithelial permeability, the effects of GIPET on the human intestine were shown to be rapid, short-lived and reversible in vivo. These data suggest that GIPET formulations have genuine potential as a platform technology for safe and effective oral drug delivery of a wide range of poorly permeable drugs.     

一种新型脑科吸引器头的制作与应用

脑组织柔软质脆,负责不同的功能区,血供丰富,因此,在脑科手术中吸引是非常重要的.吸引器头不能对脑组织造成接触性损伤,吸力大小必须适宜,大了可能吸走脑组织,小了出血吸不干净,影响视野,不利于手术的顺利进行.现介绍一种新型的吸引器头的制作与应用.     

BLOOD BRAIN BARRIER IN RIGHT- AND LEFT-PAWED FEMALE RATS ASSESSED BY A NEW STAINING METHOD

The asymmetrical breakdown of the blood-brain barrier (BBB) was studied in female rats. Paw preference was assessed by a food reaching test. Adrenaline-induced hypertension was used to destroy the BBB, which was evaluated using triphenyltetrazolium (TTC) staining of the brain slices just after giving adrenaline for 30 s. In normal rats, the whole brain sections exhibited complete staining with TTC. After adrenaline infusion for 30 s, there were large unstained areas in the left brain in right-pawed animals, and vice versa in left-pawed animals. Similar results were obtained in seizure-induced breakdown of BBB. These results were explained by an asymmetric cerebral blood flow depending upon the paw preference in rats. It was suggested that this new method and the results are consistent with contralateral motor control that may be important in determining the dominant cerebral hemisphere in animals.     

Identification of an HLA-A*0201-restrictive CTL epitope from MUC4 for applicable vaccine therapy

Recent research has indicated that MUC4 plays an important role in the development of many tumors and may prove useful as a novel cancer immunotherapy target. We aimed to identify HLA-A*0201-restrictive cytotoxic T lymphocyte (CTL) epitopes of the cancer-associated antigen MUC4. The MUC4 sequence was scanned for immunogenic peptides using HLA-binding prediction software. Dendritic cells (DCs) from peripheral blood mononuclear cells (PBMCs) were induced by cytokines. Five possible CTL epitopes were selected by software analysis, synthesized, and used to pulse mature DCs. The CD8⁺ T cells from PBMCs from an HLA-A*0201 healthy donor were stimulated with autologous MUC4-peptide-loaded DCs and expanded in vitro. T cell activation was assessed by ELISPOT, and cytotoxicity was determined by ⁵¹chromium (⁵¹Cr)-release assays. Our results show that CTLs induced by peptide P01204 could lyse T2 cells pulsed with peptide P01204 and HCT-116 cells (MUC4⁺, HLA-A2⁺). Compared with a control peptide, P01204 increased the number of IFN-γ producing T cells. Overall, these results suggest that P01204 is a novel HLA-A*0201-restrictive CTL epitope of the cancer-associated antigen MUC4. This will provide a foundation for the development of tumor-specific peptide vaccines.     

In silico analysis of antifungal peptides

Antimicrobial peptides are short peptides (< 100 amino acids) that have a potent function against microbial invasion. These peptides are produced by various organisms, including bacteria, fungi, flowering and non-flowering plants, insects and mammals. Antifungal peptides are a major group of antimicrobial peptides that have a specially potent effect against fungi. Several parameters affect the activity of antifungal peptides, including the sequence, size, charge, degree of structure formation, cationicity, hydrophobicity and amphipathicity. By analysis of numerous antifungal peptide sequences, the roles of these parameters in the structure of antifungal peptides are investigated in this review and by the in silico analysis of the existing residues, occupying each position of sequence, a template sequence is defined to generate potent and efficient lead antifungal peptides.     

Identification of a methicillin-resistant Staphylococcus aureus inhibitory compound isolated from Serratia marcescens

In this study, we identified an antimicrobial compound produced by the Gram-negative bacterium Serratia marcescens. Colonies of S. marcescens inhibited the growth of nine different methicillin-resistant Staphylococcus aureus (MRSA) isolates and several other tested Gram-positive bacterial species, but not Gram-negative bacteria. Genetic analysis revealed the requirement for the swrW gene which codes for a non-ribosomal peptide synthetase that generates the cyclodepsipeptide antibiotic serratamolide, also known as serrawettin W1. This is the first report describing the anti-MRSA properties of serratamolide.     

纳洛酮对心肺复苏后昏迷患者脑复苏的疗效观察

目的：探讨静脉反复间断推注纳洛酮，对心肺复苏（CPR）后昏迷患者脑复苏的临床作用效果。方法：从2009年9月～2012年4月我院对118例心肺复苏后昏迷患者，治疗组60例给予必要脑部基础治疗外，静脉推注（3～5min内）纳洛酮注射液2mg，间隔30min反复，经24h观察其催醒疗效，若无效（即未复苏）继续静脉给纳洛酮2mg，间隔1h反复，48h后再观察疗效，并与仅用必要的脑部基础治疗的对照组（58例）比较疗效，观察不良反应。结果：治疗组治疗前后脑复苏明显（P〈O．05）；治疗组与对照组比较疗效显著（P〈0．05）。不良反应轻微。结论：静脉反复推注纳洛酮对0肺复苏成功后无意识患者具有催醒加快脑复苏功效，提高脑复苏成功率，改善患者的生存生活质量。