Rectosigmoid Motility in Patients with Quiescent and Active Ulcerative Colitis

We studied the pathophysiology of diarrhea in ulcerative colitis by evaluating and comparing rectosigmoid motility before, during, and after a 900-cal meal in healthy subjects, patients with quiescent ulcerative colitis, and patients with active ulcerative colitis. Three intraluminal pressure transducers were used for recording of rectosigmoid motility. Motility during fasting, eating, and after eating a meal was similar in patients with quiescent disease and controls. Motility increased significantly during eating in controls, but not in patients with quiescent disease. In patients with active colitis, motility was significantly reduced during fasting, eating, and after eating, compared with controls. Motility increased significantly during eating in patients with active disease. Propagated activity was similar in the three study groups; therefore, the decreased motility was due to decrease in segmental contractions. These findings suggest that diarrhea in patients with active colitis may be related to the loss of normal segmental contractions which delay distal stool transport.     

Reduction of serum matrix metalloproteinase 1 and matrix metalloproteinase 3 in rheumatoid arthritis patients following anti- tumour necrosis factor-alpha (cA2) therapy

Matrix metalloproteinase (MMP)-1 and MMP-3 levels were measured in serum samples from rheumatoid arthritis (RA) patients undergoing a double-blinded placebo-controlled trial with the chimaeric anti-tumour necrosis factor (TNF)-alpha antibody cA2. Both MMP-1 (P < 0.015), but to a larger extent MMP-3 (P < 0.001) levels were elevated in all RA patients prior to the commencement of the trial compared with normal control sera. Following cA2 therapy, MMP-1 and MMP-3 levels were assessed in the placebo, and 1 and 10 mg/kg cA2-treated groups at 7, 14, 21 and 28 days. In both the 1 and the 10 mg/kg cA2-treated groups, a significant decrease in serum MMP-3 levels at all time points was observed, reducing maximally to 41% of pre-infusion values at day 7. MMP-1 levels were also reduced, but less dramatically than MMP-3, to 85% of pre-infusion values after 14 days in the 10 mg/kg cA2 treated group. In a separate non-placebo-controlled study, we also evaluated the tissue inhibitor of metalloproteinase (TIMP)-1 levels in plasma following cA2 infusion. Pre-infusion TIMP-1 levels were above the normal control range, but were significantly reduced (P < 0.035) 14 days after infusion to 72% of pre-infusion values. This study confirms previous reports that MMP-3 levels are elevated and correlate with measures of inflammation in RA, and furthermore demonstrate that serum MMP-3 and MMP-1 levels are downmodulated following anti-TNF-alpha antibody therapy. Whilst serum MMP-3 levels correlated with C-reactive protein (CRP) both prior to and following anti-TNF-alpha antibody therapy, it remains to be demonstrated that serum MMP-3 and/or MMP-1 levels reflect the cartilage and bone resorptive processes which are evident in this disease.      

A rapid reversed phase high performance liquid chromatographic method for the determination of docetaxel (Taxotere®) in human plasma using a column switching technique

A rapid, simple and sensitive isocratic high performance liquid chromatography (HPLC) method was developed to measure the concentration of docetaxel in plasma samples with UV detection at 227 nm. The method uses a column switching technique with an Ultrasphere C₁₈ column (75×4.6 mm ID, 3μ, Altex, USA) as clean-up column and a CSC-nucleosil C₈ column (150×4.6 mm ID, 5μ, CSC, Montreal, Canada) as the analytical column. The mobile phase consisted of Phosphate buffer (30 mM, pH=3)-acetonitrile (47:53, v/v) with the flow rates of 1.1 and 1.3 ml min⁻¹ for clean-up and analytical columns, respectively. Paclitaxel was used as an internal standard. The plasma samples were extracted using a solid phase extraction method with Ammonium acetate (30 mM, pH=5)-acetonitrile (50:50, v/v) as final eluent. The extraction method showed a recovery of 92% for docetaxel. In this system, the retention times of docetaxel and Paclitaxel were 7.2 and 8.5 min, respectively. The detection limit of docetaxel in plasma is 2.5 ng ml⁻¹. This analytical method has a very good reproducibility (7.2% between-day variability at a concentration of 10 ng ml⁻¹). It is applicable in clinical and pharmacokinetic studies.     

Pressure tuning infrared spectroscopic study of cisplatin-induced structural changes in a phosphatidylserine model membrane.

The dynamic effect of cis-diamminedichloroplatinum(II) (DPP) and its aquated metabolite (DDP-OH) on a dimyristoylphosphatidylserine (DMPS) model membrane was investigated by pressure tuning vibrational spectroscopy. The native species (DDP-Cl) and the aquated species (DPP-OH) were both observed to bind to the carboxylate group of the serine as evidenced by a frequency shift of 1622-1620 cm-1. However, only DDP-OH was observed to bind to the phosphate group (PO(-)2). The binding of either drug to DMPS resulted in an increased pressure required to halt the reorientational fluctuations of the acyl chains, indicating that the distance between the chains were increased. The two drugs did not partition into the matrix of the hydrophobic section in the model membrane. Collectively, these data suggest that DDP-Cl and DDP-OH are capable of binding to the polar head group of DMPS, resulting in an enlargement of the area of the head and a subsequent increase in the intermolecular distance between the acyl chains.     

神经肽DGAVP和Org2766对神经细胞内游离Ca2+的影响

运用Ca²⁺指示剂Fura-2作为细胞内钙离子的荧光探针,利用AR—CM—MIC阳离子测定系统,检测了分离的神经细胞内游离钙及其变化,并观测了DGAVP和Org2766对蛋白质合成抑制剂茴香霉素(ANI)引起细胞内钙离子浓度([Ca²⁺]_i)变化的影响。结果表明茴香霉素可使[Ca²⁺]_i显著升高,且有量效关系;DGAVP本身并不引起[Ca²⁺]_i发生显著变化,但适当剂量的DGAVP可显著对抗一定剂量范围内ANI升高[Ca²⁺]_i的作用,提示DGAVP对抗ANI的蛋白质合成抑制效应可能是通过拮抗ANI升高[Ca²⁺]_i这一途径实现的,另一神经肽Org2766则可能不是通过这一机制发生作用。从细胞内Ca²⁺的角度看,这两种肽的作用机理显然是不同的。     

Neonatal treatment with 192 IgG-saporin produces long-term forebrain cholinergic deficits and reduces dendritic branching and spine density of neocortical pyramidal neurons

The role of basal forebrain-derived cholinergic afferents in the development of neocortex was studied in postnatal rats. Newborn rat pups received intraventricular injections of 192 IgG-saporin. Following survival periods ranging from 2 days to 6 months, the brains were processed to document the cholinergic lesion and to examine morphological consequences. Immunocytochemistry for choline acetyltransferase (ChAT) and in situ hybridization for ChAT mRNA demonstrate a loss of approximately 75% of the cholinergic neurons in the medial septum and nucleus of the diagonal band of Broca in the basal forebrain. In situ hybridization for glutamic acid decarboxylase mRNA reveals no loss of basal forebrain GABAergic neurons. Acetylcholinesterase histochemistry demonstrates a marked reduction of the cholinergic axons in neocortex. Cholinergic axons are reduced throughout the cortical layers; this reduction is more marked in medial than in lateral cortical areas. The thickness of neocortex is reduced by approximately 10%. Retrograde labeling of layer V cortico-collicular pyramidal cells reveals a reduction in cell body size and also a reduction in numbers of branches of apical dendrites. Spine densities on apical dendrites are reduced by approximately 20-25% in 192 IgG- saporin-treated cases; no change was detected in number of spines on basal dendrites. These results indicate a developmental or maintenance role for cholinergic afferents to cerebral cortical neurons.      

Effect of Carbonated Water on Gastric Emptying and Intragastric Meal Distribution

Carbonated water has long been advocated torelieve dyspeptic symptoms, suggesting that it may altergastric motility via gastric distension. This studyaimed to determine the effect of carbonated water on gastric emptying of a radiolabeled mixedmeal in eight healthy volunteers. Meal emptying and itsdistribution within the stomach were assessed withcarbonated and still water in a crossover study.Emptying of both solid and liquid, including theduration of the lag phase, was identical for bothdrinks. However, the proximal stomach contained agreater proportion of solids (74 ± 7% vs 56± 8%, P < 0.05) and liquids (43 ± 5% vs 27 ± 4%, P < 0.05)with carbonated water as opposed to still water.Retention of the meal within the proximal stomach endedwith the lag phase and was likely related to proximaldistension. In conclusion, carbonated water did not alter overall gastricemptying but profoundly modified intragastricdistribution of the meal.     

双胸蚯蚓溶栓酶对沙鼠缺血额叶皮质超微结构及离子的影响

采用结扎沙土鼠双颈总动脉20分钟后恢复血流制做脑缺血再灌注模型。应用透射电镜对额叶皮质超微结构进行观察,并采用电镜能谱技术对神经元随机检测Na~十Ca~卄等离子含量。结果表明,缺血的对照组神经元Na~十明显增高达16.43,而缺血后腹腔注入双胸蚯蚓溶栓酶的实验组显著下降为13.02,接近正常组的11.47;Ca~卄正常组为1.03,对照组增高达3.81,而实验组下降为2.44。同时实验组超微结构的损伤性改变明显轻于对照组。     

Inhibition of some spontaneous secretory processes in macrophages and fibroblasts by ammonium chloride

Ammonium chloride inhibits the spontaneous secretion of lysozyme by mouse macrophages and the murine macrophage-like cell line P388D1 and the spontaneous secretion of lysosomal enzymes by P388D1 cells, normal human fibroblasts and the hypersecretory mucolipidosis II (I-cell) fibroblasts. NH4Cl can also inhibit protein synthesis, but this is shown to occur mainly at higher concentrations, or after longer periods of exposure, than are needed for the inhibition of the spontaneous secretory processes. It is confirmed that this amine can also interfere with the continuous endocytosis of fluid in the murine cell types. The nature of the inhibitions is discussed.