5种解热镇痛药的胶束电动毛细管色谱分离研究

报告了5种解热镇痛药——安替比林、4-氨基安替比林、安基比林、安乃近和保泰松的胶束电动毛细管色谱分离、紫外吸收检测法。研究了pH值、有机改性剂(甲醇)和十二烷基硫酸钠(SDS)浓度对分离的影响。在40mmol·L^-1SDS—25mmol·L^-1硼砂—15%甲醇(pH10.5)电泳介质中电泳,上述5组分可达基线分离。迁移时间批内和批间的RSD值分别小于1.3%和2.1%(n=5)。分离的理论塔板数在1.83×10⁴～4.15×10⁴之间。     

The use of microarray technologies in clinical oncology

Purpose

Based on previous studies that demonstrated the safety profile and preliminary clinical activity of prostate specific antigen (PSA) targeted therapeutic vaccines, as well as recent laboratory data supporting the value of the addition of co-stimulatory molecules B7-1, ICAM-1, and LFA-3 (designated TRICOM?) to these vaccines, we conducted a Phase I study to evaluate the safety and immunogenicity of a novel vaccinia and fowlpox vaccine incorporating the PSA gene sequence and TRICOM.

Methods

In this study, ten patients with androgen independent prostate cancer with or without metastatic disease were enrolled. Patients were treated with 2 × l0⁸ pfu of a recombinant vaccinia virus vaccine (PROSTVAC-V) followed by 1 × 10⁹ pfu of the booster recombinant fowlpox virus (PROSTVAC-F) both with gene sequences for PSA and TRICOM. The mean age of patients enrolled in the study was 70 (range 63 to 79). The mean PSA at baseline was 434 (range 9 – 1424).

Results

There were no deaths, and no Grade 3 or 4 adverse events. The most commonly reported adverse events, regardless of causality, were injection site reactions and fatigue. One serious adverse event (SAE) occurred that was unrelated to vaccine; this patient developed progressive disease with a new sphenoid metastasis. PSA was measured at week 4 and week 8. Four patients had stable disease (with less than 25% increase in PSA) through the week 8 study period. Anti-PSA antibodies were not induced with therapy: however, anti-vaccinia titers increased in all patients.

Conclusion

This study demonstrated that vaccination with PROSTVAC-V and PROSTVAC-F combined with TRICOM is well-tolerated and generated an immune response to vaccinia. Therefore, PROSTVAC-VF/TRICOM represents a feasible therapeutic approach for further phase II and III study in patients with prostate cancer.     

Clinical “case series”: a concept analysis

Objectives

To analyze the concept of “case series” in the medical literature compared with case reports.

Methods

A PubMed search for articles published during 2009 which had “case series” in their title was performed. A total number of 621 articles were retrieved. 586 papers were included in the analysis and 35 were excluded (18 were commentary letters, 5 were not in English, and twelve could not be retrieved by our Library). The number of patients and category of these articles were analyzed.

Results

The median (range) of the number of cases of articles having “case series” in their title was 7 (1–6432) cases. 186/ 586 articles had less than 5 cases (31.7%, 95% CI (28.3–35.1%)). The median (range) of the number of cases of articles having “case report” as their publication type was 4 (1–178) cases. Out of the 219 articles categorized as case reports 114 (52.1%, 95% CI (45.6–58.6%)) had less than five cases.

Conclusions

The concept of “case series” is not well defined in the literature and does not reflect a specific research design. We suggest that a case series should have more than four patients while four paitents or less should be reported individually as case reports.     

Using entropy of drug and protein graphs to predict FDA drug-target network: theoretic-experimental study of MAO inhibitors and hemoglobin peptides from Fasciola hepatica

There are many drugs described with very different affinity to a large number of receptors. In this work, we selected Drug-Target pairs (DTPs/nDTPs) of drugs with high affinity/non-affinity for different targets like proteins. Quantitative Structure-Activity Relationships (QSAR) models become a very useful tool in this context to substantially reduce time and resources consuming experiments. Unfortunately, most QSAR models predict activity against only one protein. To solve this problem, we developed here a multi-target QSAR (mt-QSAR) classifier using the MARCH-INSIDE technique to calculate structural parameters of drug and target plus one Artificial Neuronal Network (ANN) to seek the model. The best ANN model found is a Multi-Layer Perceptron (MLP) with profile MLP 32:32-15-1:1. This MLP classifies correctly 623 out of 678 DTPs (Sensitivity = 91.89%) and 2995 out of 3234 nDTPs (Specificity = 92.61%), corresponding to training Accuracy = 92.48%. The validation of the model was carried out by means of external predicting series. The model classifies correctly 313 out of 338 DTPs (Sensitivity = 92.60%) and 1411 out of 1534 nDTP (Specificity = 91.98%) in validation series, corresponding to total Accuracy = 92.09% for validation series (Predictability). This model favorably compares with other LDA and ANN models developed in this work and Machine Learning classifiers published before to address the same problem in different aspects. These mt-QSARs offer also a good opportunity to construct drug-protein Complex Networks (CNs) that can be used to explore large and complex drug-protein receptors databases. Finally, we illustrated two practical uses of this model with two different experiments. In experiment 1, we report prediction, synthesis, characterization, and MAO-A and MAO-B pharmacological assay of 10 rasagiline derivatives promising for anti-Parkinson drug design. In experiment 2, we report sampling, parasite culture, SEC and 1DE sample preparation, MALDI-TOF MS and MS/MS analysis, MASCOT search, MM/MD 3D structure modeling, and QSAR prediction for different peptides of hemoglobin found in the proteome of the human parasite Fasciola hepatica; which is promising for anti-parasite drug targets discovery.     

HPLC和络合-UV法测定特非那丁颗粒剂的含量

目的：用ＨＰＬＣ和电荷转移络合ＵＶ法分别测定特非那丁粒剂的含量,并对测定结果进行比较,方法：ＨＰＬＣ法,色谱柱：ＳｐｈｅｒｉｓｏｒｂＣ８（１５０＊４．６ｍｍ,５μｍ）;流动相：甲醇－０．１ｍｏｌ／Ｌ三乙胺磷酸缓冲液（８０：２０）,检测波长２３５ｎｍ。电荷转移络合ＵＶ法,利用碘与ＴＦＮ在氯仿中形成电荷转移络合物的原理,在紫外２９４ｎｍ的波长处测定ＴＦＮ的含量。结果：两法测定的线性范围和平均回收率分别     

Mycosis fungoides and Sézary syndrome: Current challenges in assessment,management and prognostic markers

Mycosis fungoides and Sézary syndrome are the most common variants of the cutaneous T‐cell lymphomas. Assessment of a patient with a suspected diagnosis requires thorough history taking and physical examination, in combination with skin biopsy. In some cases flow cytometry, molecular studies and imaging are also required in order to diagnose and stage the disease. Staging is derived from the tumour‐node‐metastasis‐blood classification and is currently our best attempt to stratify prognosis and hence guide management in this complex disease. Many other clinical, biological and pathological factors may help to distinguish groups at risk and predict prognosis more accurately. Management remains heavily guided by staging, such that patients with early‐stage disease generally begin treatment with skin‐directed or local therapies and those with advanced‐stage disease have many treatment options, including chemotherapy, the use of biological agents, local and total body radiotherapy, as well as haematopoietic stem cell transplantation. Besides staging, many other patient‐related factors influence the treatment strategy, particularly where symptom relief is paramount. There are many challenges remaining in the study of Mycosis fungoides and Sézary syndrome and, given the rarity of the disease, concerted worldwide efforts are required to conduct efficient and effective research.