顺铂聚乳酸微球的药物释放特性及肝动脉栓塞研究

对顺铂聚乳酸微球进行了体外药物释放和家犬肝动脉栓塞研究。该微球粒径范围为50～200μm,平均粒径为115.76±35.94μm,顺铂含量为37.16%(W/W);体外药物释放机制符合Higuchi方程;肝动脉栓塞后8h,肝组织顺铂浓度高达21.55±12.18μg/g,明显高于肝动脉灌注顺铂组:3.16±0.09μg/g(P<0.05);肝动脉栓塞组的顺铂血浓峰值、各取血点浓度及曲线下面积AUC皆低于肝动脉灌注顺铂组。可望达到提高栓塞部位的药物疗效,降低全身毒副反应的作用。     

Anti-CD40 antibody stimulates the VLA-4-dependent adhesion of normal and LFA-1-deficient B cells to endothelium.

We have demonstrated that anti-CD40 antibody stimulates the heterotypic adhesion of B cells to endothelial cells. This has been shown by using normal B lymphocytes and B-cell lines in a quantitative adhesion assay. When B cells, B-cell lines and Epstein-Barr virus (EBV)-transformed B cells from a patient with leucocyte adhesion deficiency (LAD) were stimulated with anti-CD40 antibody, they were found to adhere to both untreated and interleukin-1 (IL-1)-stimulated human umbilical vein endothelial cells (HUVEC), and to the lung carcinoma line A549. To identify the adhesion receptors responsible for this anti-CD40-induced adhesion, cells were pretreated with blocking antibodies prior to assay. Our results indicate that anti-CD40-stimulated adhesion of tonsillar B cells, B-cell lines RPMI-8866, JY, and an EBV-transformed LAD-cell line were predominantly dependent on the very late antigen-4 (VLA-4)-vascular cell adhesion molecule (VCAM) interaction. Anti-CD40-induced adhesion appears to be dependent on the activation of protein tyrosine kinase and protein kinase C and on the presence of divalent cations.     

Differential ontogenesis of type I and II benzodiazepine receptors in mouse cerebellum

The ontogeny of type I and type II benzodiazepine binding sites was studied in mouse cerebellum by displacement of [3H]flunitrazepam binding by zolpidem, a ligand specific for the type I sites. Type I binding sites predominate throughout development and in the adult while type II sites account for 25% of total cerebellar benzodiazepine binding sites at birth and, during development, decrease to 10% or less in the adult. On a per cerebellum basis type II sites increase during the first postnatal week and then remain at a steady level while type I sites increase until adulthood. These results may indicate a specific localization of the type II sites (and of the corresponding alpha-protein subunits in the GABA/benzodiazepine receptor complex) in structures already present at birth and developing during a short early postnatal period. The affinity of zolpidem for its high affinity (type I) binding sites increases during cerebellar ontogeny, this increase possibly indicates an epigenetic (post-translational) 'maturation' process of the corresponding receptor molecule. Hill numbers indicate the existence of an additional binding site heterogeneity greater during development but still present in the adult; probably this is to be related to the simultaneous presence of different 'maturation' stages during development and with a certain variety of the final products.     

An Unexplained Death: Hannah Greener and Chloroform

Background: Reports of major and minor sequelae following lidocaine spinal anesthesia have generated interest in an alternative short-acting intrathecal agent. Of the available anesthetics suitable for short-duration spinal anesthesia, prilocaine is perhaps the most promising agent. However, data comparing the neurotoxicity of these agents are lacking. Accordingly, the present experiments investigate whether prilocaine and lidocaine differ with respect to sensory impairment and histologic damage when administered intrathecally in the rat.

Methods: Ninety rats were divided into three groups to receive an intrathecal infusion of 2.5% prilocaine in saline, 2.5% lidocaine in saline, or normal saline. The animals were assessed for persistent sensory impairment 4 days after anesthetic administration using the tail-flick test. Three days later, the animals were killed, and specimens of the spinal cord and nerve roots were obtained for histopathologic examination.

Results: Prilocaine and lidocaine produced equivalent elevations in tail-flick latency that differed significantly from saline. Histologic injury scores with prilocaine were greater than with lidocaine, but this difference did not reach statistical significance.     

Primary tuberculous nasal polypi—A case report

Primary tuberculous pathology in nasolpolypi is a rare condition. A case of bilateral ethmoidal polypi with tubercular lesion diagnosed on histopathologlcal examination is being reported and the available relevant literature has been reviewed.     

Predictive, error-compensating kinetic method for enzymatic quantification of creatinine in serum

Here we describe an error-compensating kinetic-based method for the enzymatic quantification of creatinine in serum. The method, which has a large linear range and very low dependency on experimental variables that influence enzyme activity, is based on the use of creatinine amidohydrolase in a four-step coupled reaction sequence to generate a product that is monitored photometrically. We collected data for absorbance vs time during two to four half-lives of each reaction and fit a first-order model to the data to compute the total absorbance change that would be measured if the reaction were monitored to completion. Computed values of absorbance change agreed well with measured values and varied linearly with creatinine concentration in the sample throughout the range examined: 44 to 1326 mumol/L. A twofold change in enzyme activity in the final reaction mixture (3.3 to 6.6 kU/L) produced changes of only 12% and 4% for creatinine concentrations of 44 and 353 mumol/L, respectively. Results (y) for 39 serum samples that contained creatinine concentrations between 20 and 1800 mumol/L agreed well with liquid-chromatographic results (x), yielding linear least-squares statistics of y = (1.03 +/- 0.01) x + (5 +/- 5) mumol/L (r = 0.995, Sy.x = 37 mumol/L). We conclude that the predictive kinetic approach is a robust method for the quantification of creatinine in serum.     

Development of an alloantiserum (R2) that detects susceptibility of chickens to subgroup E endogenous avian leukosis virus

An alloantiserum, termed R2, specifically agglutinates red blood cells (RBC) from line 100B chickens that are susceptible to avian leukosis viruses (ALV) belonging to subgroups B and E, but does not agglutinate RBC from congenic inbred line 7(2 )chickens that are resistant to ALV B and E. The R2 antigen was also detected on lymphocytes and thrombocytes. Using chickens from a special cross, it was found that R2 reactivity requires that the chickens must: (1) be susceptible to infection by ALV-E; and (2) express a viral envelope gene with subgroup E specificity. With R2 antiserum, a nearly perfect association was observed between agglutination and susceptibility to ALV-B in F(2) chickens containing endogenous viral genes ev2 and/or ev3. These results support earlier evidence that ALV-B and ALV-E share receptors. Moreover, the R2 antiserum was shown to neutralize ALV-E. The R2 antigen showed Mendelian segregation in chickens of a commercial White Leghorn strain-cross containing ev3, ev6 and ev9. However, commercial chickens with or without the R2 antigen did not differ in susceptibility to lymphoid leukosis induction or immune response on infection with ALV of subgroup A for complex reasons we discuss.     

Effects of instruction by practice assistants on inhaler technique and respiratory symptoms of patients. A controlled randomized videotaped intervention study

BACKGROUND: Many patients with asthma or chronic obstructive pulmonary diseaseuse their medication inhalers incorrectly. General practitioners,pharmacists and other health care providers do not always havethe opportunity to instruct patients in correct inhaler technique. OBJECTIVE: To find out whether the inhaler technique and respiratory symptomsof patients can be improved after instruction by practice assistants. METHODS: Single blind, randomized intervention study in which 48 patientswho had been using a dry powder inhaler for at least one monthtook part. Their inhaler technique was videotaped on two visitswith a two-week interval between visits. The inhaler techniqueon the videos was subsequently scored by two experts on ninecriteria. At both visits the patients completed a questionnaireabout their respiratory symptoms. After the first video, 25patients were randomly chosen to receive instruction from oneof six practice assistants who had followed a one evening courseabout inhaler instruction, and who had been issued an instruction-set. RESULTS: The patients who received instruction had a significantly greaterreduction in number of mistakes at the second visit than thepatients who did not (P = 0.01). The instructed patients alsoreported less dyspnoea at the second visit (P = 0.03). No effectof instruction was found on wheezing, cough and sputum production. CONCLUSION: The inhaler technique of patients can be improved significantlyby the instruction of patients by trained practice assistants,possibly resulting in less dyspnoea. Keywords. Administration-inhalation, obstructive lung diseases, airways symptoms, patient-education, general practice.