A phase I trial of immunostimulatory CpG 7909 oligodeoxynucleotide and 90yttrium ibritumomab tiuxetan radioimmunotherapy for relapsed B‐cell non‐Hodgkin lymphoma

Radioimmunotherapy (RIT) for relapsed indolent non‐Hodgkin lymphoma produces overall response rates (ORR) of 80% with mostly partial remissions. Synthetic CpG oligonucleotides change the phenotype of malignant B‐cells, are immunostimulatory, and can produce responses when injected intratumorally and combined with conventional radiation. In this phase I trial, we tested systemic administration of both CpG and RIT. Eligible patients had biopsy‐proven previously treated CD20+ B‐cell NHL and met criteria for RIT. Patients received rituximab 250 mg/m² days 1,8, and 15; ¹¹¹In‐ibritumomab tiuxetan days 1, 8; CpG 7909 days 6, 13, 20, 27; and 0.4 mCi/kg of ⁹⁰Y‐ibritumomab tiuxetan day 15. The doses of CpG 7909 tested were 0.08, 0.16, 0.32 (six patients each) and 0.48 mg/kg (12 patients) IV over 2 hr without dose limiting toxicity. The ORR was 93% (28/30) with 63% (19/30) complete remission (CR); median progression free survival of 42.7 months (95% CI 18‐NR); and median duration of response (DR) of 35 months (4.6–76+). Correlative studies demonstrated a decrease in IL10 and TNFα, and an increase in IL1β, in response to therapy. CpG 7909 at a dose of 0.48 mg/kg is safe with standard RIT and produces a high CR rate and long DR; these results warrant confirmation. Am. J. Hematol. 88:589–593, 2013. © 2013 Wiley Periodicals, Inc.     

Polymer-tethered glyconanoparticle colourimetric biosensors for lectin binding: structural and experimental parameters to ensure a robust output

Glycan–lectin interactions play essential roles in biology; as the site of attachment for pathogens, cell–cell communication, and as crucial players in the immune system. Identifying if a new glycan (natural or unnatural) binds a protein partner, or if a new protein (or mutant) binds a glycan remains a non-trivial problem, with few accessible or low-cost tools available. Micro-arrays allow for the interrogation of 100''s of glycans but are not widely available in individual laboratories. Biophysical techniques such as isothermal titration calorimetry, surface plasmon resonance spectrometry, biolayer interferometry and nuclear magnetic resonance spectroscopy all provide detailed understanding of glycan binding but are relatively expensive. Glycosylated plasmonic nanoparticles based on gold cores with polymeric tethers have emerged as biosensors to detect glycan–protein binding, based on colourimetric (red to blue) outputs which can be easily interpreted by a simple UV-visible spectrometer or by eye. Despite the large number of reports there are no standard protocols for each system or recommended start points, to allow a new user to deploy this technology. Here we explore the key parameters of nanoparticle size, polymeric tether length and gold concentration to provide some guidelines for how polymer-tethered glycosylated gold nanoparticles can be used to probe a new glycan/protein interactions, with minimal optimisation barriers. This work aimed to remove the need to explore chemical and nanoparticle space and hence remove a barrier for other users when deploying this system. We show that the concentration of the gold core is crucial to balance strong responses versus false positives and recommend a gold core size and polymer tether length which balances sufficient colloidal stability and output. Whilst subtle differences between glycans/lectins will impact the outcomes, these parameters should enable a lab user to quickly evaluate binding using minimal quantities of the glycan and lectin, to select candidates for further study.

Polymer tethered glycosylated gold nanoparticles are optimised to provide a starting point to evaluate glycan–lectin interactions.     

超滤工艺对风痛宁注射液中有效成分的影响

目的：采用正交试验方法,研究超滤工艺对风痛宁注射液有效成分的影响。方法：以温度、pH值、药液浓度和超滤膜截留分子量4因素进行正交设计,盐酸青藤碱为检测指标,测定超滤前后药液成分浓度,通过计算透过率来观察盐酸青藤碱超滤前后的含量变化。结果：温度、pH值、药液浓度和超滤膜截留分子量4个考察因素对盐酸青藤碱透过率无显著影响。结论：风痛宁注射液有效成分进行超滤的适用性较好。     

经皮肾镜取石术的研究现状及并发症防治策略

回顾分析了近几年有关经皮肾镜取石术(PCNL)的文献,对其在通道大小,体位摆置,定位方法,碎石方式等方面不同选择的优劣进行了总结和评价,同时从导致PCNL并发症的原因出发,探讨其防治策略的有效性。     

苦参生物碱的高效液相色谱法测定

报道了苦参中五种主要生物碱——槐果碱、苦参碱、槐定、氧化槐果碱和氧化苦参碱的高效液相色谱测定法。用氨基键合相柱,乙腈—磷酸水溶液(pH 2)—无水乙醇(80:8:10)为流动相,220nm为检测波长。方法简便易行,可在15 min内完成测定。     

PSORIASIS-LIKE LESIONS IN GUINEA PIGS RECEIVING PROPRANOLOL

Background. β-Blockers cause a psoriasiform eruption. We investigated the skin effects of systemic propranolol in a formal protocol. Methods. Propranolol, 0.1 mg/day, was used systemically by gavage in eight albino guinea pigs. Normal saline was given to another group of seven guinea pigs. Results. Propranolol produced psoriasiform lesions in five of seven guinea pigs on the 30th day. Biopsies showed acanthosis, parakeratosis, microabscesses, and cellular infiltration of upper dermis. Topical application of propranolol did not produce clinical psoriasiform changes, while acanthosis and papillomatosis was observed in six of the six guinea pigs. Conclusions. Systemically given propranolol can lead to psoriasis-like lesions, which might be due to a serum factor.     

A PIL for every ill? Patient information leaflets (PILs): a review of past, present and future use

This article reviews the usefulness and importance of written information, specifically leaflets, being given to patients. Evidence suggesting how both patient and doctor may benefit from the giving of written information is reviewed. Identification of good practice relating to the content and readability of leaflets is discussed. An argument is put forward that the giving of written information is an under-utilized resource in contributing to improving patient outcomes but that this may be changing with the increasing use of patient leaflet databases. The advantages and disadvantages of computer- generated patient leaflets are discussed and desirable further areas of research on computer-generated leaflets are proposed.      

Effects of Arecoline on Calcium Channel Currents and Caffeine-induced Calcium Release in Isolated Single Ventricular

The cholinergic system plays an importantrole in the control of heart rate and myocardialcontractility[1] .The inotropic and chronotropic ef-fects are partly regulated by the cytosolic Ca2 + lev-el( [Ca2 + ]i) .Muscarine receptor agonist,Arecol-ine ( Are) ,is a kind of alkaloid extracted from theseeds of areca.It had been reported that Are hadnegative inotropic and negative chronotropic effectson isolated guinea pig atria[2 ] ,but its effects oncalcium mobilization was unclear. In order to i…     

Efficacy and tolerability of pantoprazole 40 mg versus 80 mg in patients with reflux oesophagitis.

BACKGROUND: Pantoprazole is a substituted benzimidazole which is a potent inhibitor of gastric acid secretion by its action upon H+, K+- ATPase. METHODS: Pantoprazole 40 mg and 80 mg were compared in a randomized double-blind study in 192 out-patients with stage II or III (Savary-Miller classification) reflux oesophagitis. Patients received either pantoprazole 40 mg (n = 97) or pantoprazole 80 mg (n = 95), once daily before breakfast for 4 weeks. Treatment was extended for a further 4 weeks if the oesophagitis had not healed. RESULTS: After 4 weeks complete healing of the reflux oesophagitis was seen in 78% of protocol-correct patients given pantoprazole 40 mg daily (n = 86), and in 72% in the 80 mg (n = 87) group. The cumulative healing rates after 8 weeks were 95 and 94%, respectively (P > 0.05, Cochran-Mantel- Haenszel), and time until healing of oesophagitis comparable in both groups. Differences between doses were also not significant in an intention-to-treat analysis. Both dosing schedules were well tolerated and the patients experienced remarkable symptom relief. No adverse event or changes in laboratory values of clinical significance could definitely be ascribed to the trial medication. CONCLUSION: The 40 mg pantoprazole dosage is comparable to 80 mg in reflux oesophagitis, both in efficacy and tolerability.