Effect of plant neutrophil elastase inhibitor on leucocyte migration, adhesion and cytokine release in inflammatory conditions

BACKGROUND AND PURPOSE

The serine and cysteine peptidase inhibitor, BbCI, isolated from Bauhinia bauhinioides seeds, is similar to the classical plant Kunitz inhibitor, STI, but lacks disulphide bridges and methionine residues. BbCI blocks activity of the serine peptidases, elastase (K_iapp 5.3 nM) and cathepsin G (K_iapp 160.0 nM), and the cysteine peptidase cathepsin L (K_iapp 0.2 nM). These three peptidases play important roles in the inflammatory process.

EXPERIMENTAL APPROACH

We measured the effects of BbCI on paw oedema and on leucocyte accumulation in pleurisy, both induced by carrageenan. Leucocyte–endothelial cell interactions in scrotal microvasculature in Wistar rats were investigated using intravital microscopy. Cytokine levels in pleural exudate and serum were measured by elisa.

KEY RESULTS

Pretreatment of the animals with BbCI (2.5 mg·kg⁻¹), 30 min before carrageenan-induced inflammation, effectively reduced paw oedema and bradykinin release, neutrophil migration into the pleural cavity. The number of rolling, adhered and migrated leucocytes at the spermatic fascia microcirculation following carrageenan injection into the scrotum were reduced by BbCI pretreatment. Furthermore, levels of the rat chemokine cytokine-induced neutrophil chemo-attractant-1 were significantly reduced in both pleural exudates and serum from animals pretreated with BbCI. Levels of interleukin-1β or tumour necrosis factor-α, however, did not change.

CONCLUSIONS AND IMPLICATIONS

Taken together, our data suggest that the anti-inflammatory properties of BbCI may be useful in investigations of other pathological processes in which human neutrophil elastase, cathepsin G and cathepsin L play important roles.     

The appropriateness of surveillance colonoscopy intervals after polypectomy

BACKGROUND:

Adherence to surveillance colonoscopy guidelines is important to prevent colorectal cancer (CRC) and unnecessary workload.

OBJECTIVE:

To evaluate how well Canadian gastroenterologists adhere to colonoscopy surveillance guidelines after adenoma removal or treatment for CRC.

METHODS:

Patients with a history of adenomas or CRC who had surveillance performed between October 2008 and October 2010 were retrospectively included. Time intervals between index colonoscopy and surveillance were compared with the 2008 guideline recommendations of the American Gastroenterological Association and regarded as appropriate when the surveillance interval was within six months of the recommended time interval.

RESULTS:

A total of 265 patients were included (52% men; mean age 58 years). Among patients with a normal index colonoscopy (n=110), 42% received surveillance on time, 38% too early (median difference = 1.2 years too early) and 20% too late (median difference = 1.0 year too late). Among patients with nonadvanced adenomas at index (n=96), 25% underwent surveillance on time, 61% too early (median difference = 1.85) and 14% too late (median difference = 1.1). Among patients with advanced neoplasia at index (n=59), 29% underwent surveillance on time, 34% too early (median difference = 1.86) and 37% later than recommended (median difference = 1.61). No significant difference in adenoma detection rates was observed when too early surveillance versus appropriate surveillance (34% versus 33%; P=0.92) and too late surveillance versus appropriate surveillance (21% versus 33%; P=0.11) were compared.

CONCLUSION:

Only a minority of surveillance colonoscopies were performed according to guideline recommendations. Deviation from the guidelines did not improve the adenoma detection rate. Interventions aimed at improving adherence to surveillance guidelines are needed.     

Parents, physicians, and antibiotic use

BACKGROUND: Emergence of resistant bacterial pathogens has increased concerns about antibiotic prescribing patterns. Parent expectations and pressure may influence these patterns. OBJECTIVE: To understand how parents influence the prescribing patterns of physicians and what strategies physicians believe are important if we are going to reduce inappropriate use of oral antimicrobial agents. DESIGNS AND METHODS: One thousand pediatricians who are members of the American Academy of Pediatrics were asked to complete a semi-structured questionnaire. The physicians were chosen randomly by the American Academy of Pediatrics. RESULTS: Nine hundred fifteen pediatricians were eligible and 610 surveys were analyzable, for a response rate of 67%. The majority of respondents were male (56%), worked in a group practice (51%), saw an average of 114 patients per week and were in practice for 14 years. Forty percent of the pediatricians indicated that 10 or more times in the past month a parent had requested an antibiotic when the physician did not feel it was indicated. Forty-eight percent reported that parents always, most of the time, or often pressure them to prescribe antibiotics when their children are ill but antibiotics are not indicated. In follow-up questions, approximately one-third of physicians reported they occasionally or more frequently comply with these requests. Seventy-eight percent felt that educating parents would be the single most important program for reducing inappropriate oral antibiotic use and 54% indicated that parental pressure, in contrast to concerns about legal liability (12%) or need to be efficient in practice (19%), contributed most to inappropriate use of oral antibiotics. CONCLUSIONS: Pediatricians acknowledge prescribing antimicrobial agents when they are not indicated. Pediatricians believe educating parents is necessary to promote the judicious use of antimicrobial agents.     

朝藿素D的分离和结构

从朝鲜淫羊藿(Epimedium koreanum)地上部分分离得到一新黄酮成分(I)和一已知化合物(II)。经光谱解析,证明I的结构为5,7,3',4'-tetrahydroxy-5'-prenylflavone,命名为朝藿素D(epimedokoreanin D);II为2-hydroxy-3,4,6,7-tetramethoxy-9,10-dihydrophenanthren。     

Intrahepatic bile duct and portal vein anatomy revisited

Seventeen normal cadaver livers were studied to assess the anatomic relationship of bile ducts to portal veins. The common bile duct, main portal vein, and hepatic artery were cannulated and injected with air, dilute contrast medium, and mineral oil, respectively. The livers were placed in anatomic position and examined with computed tomography. In the lateral segment of the left hepatic lobe, the bile ducts were anterior to the portal vein in seven cases, posterior in seven, and tortuous (ie, both anterior and posterior) in three. In the medial segment of the left lobe, the bile ducts were anterior in four cases, posterior in four, tortuous in three, and not seen in six. In the right lobe, the bile ducts were anterior in nine cases, posterior in five, tortuous in one, and not seen in two. In the porta hepatis, the bile ducts were anterior in ten cases, posterior in one, tortuous in five, and not seen in one. Histologic findings confirmed the anterior and posterior location of the bile ducts relative to the portal veins. These findings contradict the commonly held view of intrahepatic bile ducts being anterior to the portal vein and are clinically significant for techniques such as bile duct drainage.