A Potent Mimetic of the Siglec-8 Ligand 6’-Sulfo-Sialyl Lewisx

Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewis^x has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewis^x and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved.     

Clinical study in epidural injection with lappaconitine compound for post-operative analgesia

In this study, the effect and side-effect of epidural injection with lappaconitine compound for post-operative analgesia was observed. One hundred and twenty patients were randomly divided into 4 groups. Lappaconitine compound (LB) consisted of 12 mg of lappaconitine and 22.5 mg of bupivacaine, was given to group A (the group of observation), and lappaconitine 12 mg, bupivacaine 22.5 mg and morphine 2 mg to group B, C and D respectively for control. All were given by epidural injection with single blind method during post-operative pain of incision operation. Result showed that the initiating of analgesia was quicker in group A and C than that in group B and D, and the efficacy was group D > A > C > B. There was significant difference between group A and B in the above two parameters, P < 0.01 and P < 0.05. The analgisia maintenence time of single injection was D > A > B > C, that of group D was significantly longer than that of group A (P < 0.01). It indicated that the epidural injection with LB was more rapid and potent than that with lappaconitine alone in post-operative analgesia, and the former had no side-effect, it was safer than morphine.     

A linkage map of human chromosome 21:43 PCR markers at average intervals of 2.5 cM

A genetic linkage map of human chromosome 21q (HC21q) containing 43 markers genotyped by the polymerase chain reaction in the CEPH pedigrees is presented. The markers placed on this map are highly polymorphic with an average heterozygosity of 61%. The average interval size of the markers localized at 1000:1 odds is 2.5 cM. The map has a total length of 65.5 cM, with male and female lengths of 47.7 and 83.3 cM, respectively. The genotypes used in the construction of this map were subjected to rigorous error checking, which is reflected in the shorter map length compared to previous maps; the estimated error rate in genotyping is less than 0.04%. As noted in previous linkage maps there is increased recombination in females on proximal HC 21q and in the male in a region near the telomere. This map of HC 21 represents a highly informative and dense meiotic linkage map and will be useful in linking disease phenotypes to loci on this chromosome.     

Design and implementation of clinical trials of antimicrobial drugs and devices used in periodontal disease treatment

The design and implementation of clinical trials (CTs) carried out to evaluate antimicrobial and anti-infective drugs and devices are one of the most difficult challenges in contemporary periodontal research and product development. The overwhelming amount of evidence which has established a microbial etiology for periodontitis is the basis for developing and testing antimicrobial treatments. Well-designed antimicrobial CTs start with a carefully crafted hypothesis and a protocol which explicitly integrates the requirements of the patient, the clinician, the sponsor, and regulatory authorities. Surrogate variables for effectiveness must be clinically relevant, scientifically sound, and statistically valid. Currently, clinical attachment level measurements and alveolar bone assessments are accepted as proof of effectiveness. Indication and claim support of the antimicrobial product guide the design and implementation of the CT. Adverse microbiologic consequences, such as lack of antimicrobial susceptibility, wrong spectrum, incorrect dosage, non-compliance, and drug interference, must be monitored. Successful CTs balance a large group of variables used to screen, randomize, and assign subjects to experimental and control groups to ensure that prognostic and risk factors are properly accounted for.     

ERCP and CT findings of ectopic drainage of the common bile duct into the duodenal bulb

OBJECTIVE: The purpose of this study was to evaluate ERCP and CT findings of ectopic drainage of the common bile duct into the duodenal bulb. CONCLUSION: Although rare, the diagnosis of ectopic drainage of the common bile duct into the duodenal bulb is important to prevent inadvertent damage during biliary tract or gastric surgery and to clarify the cause of chronic peptic ulcers.     

Prenatal diagnosis: update addresses technological advances

This is the second in a series of articles provided to the readers of PENNSYLVANIA MEDICINE as an update from researchers and clinicians in this cutting-edge medical field. The series is partially sponsored through a grant from the Pennsylvania Department of Health to the University of Pittsburgh Department of Human Genetics.