Pyogenic granuloma: a rare side complication from an orthodontic appliance

Abstract

This case report discusses a rare side effect associated with the use of a fixed quad helix orthodontic appliance. A 14-year-old healthy girl presented with a painful enlarging mass on her tongue, which was causing distress to both her and her parents. Investigations confirmed that the mass was a pyogenic granuloma and management involved surgical excision of the mass and removal of the quad helix appliance. At least once previous case associated with an orthodontic quad helix appliance has been reported in the literature.     

Aib‐based peptide backbone as scaffolds for helical peptide mimics

Abstract: Helical peptides that can intervene and disrupt therapeutically important protein–protein interactions are attractive drug targets. In order to develop a general strategy for developing such helical peptide mimics, we have studied the effect of incorporating α‐amino isobutyric acid (Aib), an amino acid with strong preference for helical backbone, as the sole helix promoter in designed peptides. Specifically, we focus on the hdm2–p53 interaction, which is central to development of many types of cancer. The peptide corresponding to the hdm2 interacting part of p53, helical in bound state but devoid of structure in solution, served as the starting point for peptide design that involved replacement of noninteracting residues by Aib. Incorporation of Aib, while preserving the interacting residues, led to significant increase in helical structure, particularly at the C‐terminal region as judged by nuclear magnetic resonance and circular dichroism. The interaction with hdm2 was also found to be enhanced. Most interestingly, trypsin cleavage was found to be retarded by several orders of magnitude. We conclude that incorporation of Aib is a feasible strategy to create peptide helical mimics with enhanced receptor binding and lower protease cleavage rate.     

膀胱癌病人乙酰基转移酶表型的研究

应用ＤＤＳ作为实验药物，采用高效液相色谱法，研究了目前尚存话的有２－萘胺职业接触史的１１名膀胱癌病人、２５名普通膀胱癌病人及２３名接触对照的ＮＡＴ酶表型。结果表明。无论有无２－萘胺职业接触史，膀胱癌病人中慢型乙酰化者所占比例（５２．２％和４５．５％）均高于对照组（１３．０％），且差异有显著性（Ｐ＜０．０５），比值比０Ｒ分别为５．５６（９５％可信限＝１．０２～３０．３）和７．２５（９５％可信限＝１．７０～３０．３），提示慢型乙酰化者若暴露于２－萘胺更易患膀胱肿瘤，乙酰化慢表型是膀胱癌的一个遗传易感因素。     

Chemical synthesis and characterization of peptides and oligomeric proteins designed to form transmembrane ion channels

A strategy for the synthesis of peptides and oligomeric proteins designed to form transmembrane ion channels is described. A folding motif that exhibits a functional ionic pore encompasses amphipathic α-helices organized as a four-helix bundle around a central hydrophilic pore. The channel-forming activity of monomeric amphipathic peptides may be examined after reconstitution in lipid bilayers in which peptides self-assemble into conductive oligomers. The covalent attachment of channel-forming peptides to the lysine ε-amino groups of a template molecule (KKKPGKEKG) specifies oligomeric number and facilitates the study of ionic permeation and channel blockade. Here we describe detailed protocols for the total synthesis of peptides and template-assembled four-helix bundle proteins, exemplified with the sequence of M2δ (EKM-STAISVLLAQAVFLLLTSQR), considered involved in lining the pore of the nicotinic acetylcholine receptor channel. For comparison, the synthesis of a second four-helix bundle, T₄CaIVS3 with the sequence of predicted transmembrane segment S3 (DPWNVFDFLIVIGSIIDVILSE) of the fourth repeat of the l -type voltage-gated calcium channel, is included. Peptides and proteins are synthesized step-wise by solid-phase methods, purified by reversed-phase HPLC, and homogeneity ascertained by analytical HPLC, capillary zone electrophoresis, SDS/PAGE, amino acid analysis and sequencing. Optimization of synthetic procedures for hydrophobic molecules include reducing resin substitution to avoid steric hindrance and aggregation of the final product. Protocols for the preparation of the samples prior to HPLC purification as well as the conditions and columns required for successful purification are presented. The methods developed are generally applicable for the chemical synthesis, purification and characterization of amphipathic peptides and template directed helical bundle proteins.     

Synthesis and Characterization of N‐Propargyl Cinnamamide Polymers and Copolymers

This paper deals with synthesis and characterization of a novel poly(N‐propargylamide) containing cinnamamide groups (poly( 1 )) in its side chains. Monomer 1 , CH?CCH₂NHCOCH?CH(C₆H₅), was synthesized and polymerized with a rhodium catalyst, (nbd)Rh⁺B^?(C₆H₅)₄ (nbd = 2,5‐norbornadiene). Effects of some factors on polymerization of monomer 1 such as solvent, temperature, and the ratio of monomer/catalyst were investigated in detail; polymers with moderate number‐average molecular weights ( ) and low index of polydispersity ( ) were obtained. To improve the polymers' solubility and to elucidate whether poly( 1 ) could form helical conformation, another N‐propargylamide monomer 2 , CH?CCH₂NHCOCH(CH₂CH₃)₂, was employed to accomplish copolymerization with monomer 1 . Copolymerization with monomer 2 improved obviously the solubility of the (co)polymers; the copolymers with certain monomer ratios could form helices under the examined conditions according to the related UV‐vis spectra.

     

Substituted 1,4-benzodiazepine-2,5-diones as alpha-helix mimetic antagonists of the HDM2-p53 protein-protein interaction

Small molecule antagonists of protein-protein interactions represent a particular challenge for pharmaceutical discovery. One approach to finding molecules that can disrupt these interactions is to seek mimics of common protein structure motifs. We present an analysis of how molecules based on the 1,4-benzodiazepine-2,5-dione scaffold serve to mimic the side-chains presented by the hydrophobic face of two turns of an alpha-helix derived from the tumor suppressor protein p53, and thus antagonize the HDM2-p53 protein-protein binding interaction.     

Helix and Drugs: Snails for Western Health Care From Antiquity to the Present

The land helix, or snail, has been used in medicine since antiquityand prepared according to several formulations. This historicalreport traces the understanding of their properties from thetime of Hippocrates, who proposed the use of snail mucus againstprotoccle and Pliny who thought that the snail increased thespeed of delivery and was "a sovereign remedy to treat painrelated to burns, abscesses and other wounds", Galien recommendedsnails against hydrops foetails. In the 18th century, varioussnail "preparations" were also recommended for external usewith dermatological disorders and internally for symptoms associatedwith tuberculosis and nephritis. Surprisingly, the 19th centurysaw a renewed interest in the pharmaceutical and medical useof snails with numerous indications for snail preparations.This interest in snails did not stop at the end of the 19thcentury. The 1945 edition of Dorvault devotes an entire paragraphto snails, indicating that the therapeutic usage of snails wasstill alive at that time. Recently the FDA has also shown aninterest in snails. Ziconotide (SNXIII), a synthetic peptidecoming from snail venom, has been under FDA review since 1999.Pre-clinical and clinical studies of this new drug are promising.     

慢性乙型肝炎患者血清IL-12、IL-18水平和外周血单个核细胞FOXp3基因水平研究*

目的 探讨慢性乙型肝炎（CHB）患者血清白细胞介素-12（IL-12）、IL-18和外周血单个核细胞叉头蛋白P3（Foxp3）基因水平变化及其临床意义。方法 2015年7月~2018年3月我院收治的CHB患者78例和同期健康体检者25例,采用ELISA法检测血清IL-12和IL-18水平,分离外周血单个核细胞,采用RT-PCR法检测细胞Foxp3 mRNA水平。结果 在78例CHB患者中,经肝组织活检诊断G1组21例,G2组24例,G3组19例,G4组14例;CHB患者血清ALT和AST水平分别为（278.3±89.4）U/L和（305.3±84.6） U/L,显著高于健康人的[（25.3±7.6） U/L和（20.3±6.5） U/L,P<0.05];G4组血清ALT和AST水平分别为（563.5±132.4） U/L和 （513.3±102.5） U/L,显著高于G1组[（113.2±67.4）U/L和（73.5±25.3） U/L]或G2组[（153.6±45.3） U/L和（113.8±35.2） U/L]或G3组[（240.5±56.6） U/L和（156.7±51.2） U/L,P<0.05];CHB患者血清IL-12和IL-18水平及单个核细胞Foxp3 mRNA水平分别为（198.3±19.6） pg/ml、（408.6±91.2） pg/ml及（4.5±0.7）,显著高于健康人[（64.5±10.9） pg/ml、（127.3±15.7） pg/ml、（3.3±0.4）,P<0.05];G4组血清IL-12、IL-18及Foxp3基因水平分别为（237.5±23.6） pg/ml、（431.5±106.3） pg/ml、（5.1±0.3）],显著高于G1组[（146.3±15.2） pg/ml、（390.2±90.3） pg/ml、（3.7±0.6）] 或G2组[（185.2±13.6） pg/ml、（403.6±93.2） pg/ml、（3.9±0.5） pg/ml]或G3组[（203.2±18.3）pg/ml、（414.3±105.4） pg/ml、（4.3±0.7）,P<0.05]。结论 CHB患者外周血单个核细胞Foxp3基因及血清IL-12和IL-18水平显著升高,且肝组织炎症活动显著者,其水平更高,提示其参与了CHB的发病过程。及时检测这些指标可能对监测病情变化和判断治疗应答有帮助。