General solution for diffusion-controlled dissolution of spherical particles. 1. Theory.

Three classical particle dissolution rate expressions are commonly used to interpret particle dissolution rate phenomena. Our analysis shows that an assumption used in the derivation of the traditional cube-root law may not be accurate under all conditions for diffusion-controlled particle dissolution. Mathematical analysis shows that the three classical particle dissolution rate expressions are approximate solutions to a general diffusion layer model. The cube-root law is most appropriate when particle size is much larger than the diffusion layer thickness, the two-thirds-root expression applies when the particle size is much smaller than the diffusion layer thickness. The square-root expression is intermediate between these two models. A general solution to the diffusion layer model for monodispersed spherical particles dissolution was derived for sink and nonsink conditions. Constant diffusion layer thickness was assumed in the derivation. Simulated dissolution data showed that the ratio between particle size and diffusion layer thickness (a0/h) is an important factor in controlling the shape of particle dissolution profiles. A new semiempirical general particle dissolution equation is also discussed which encompasses the three classical particle dissolution expressions. The success of the general equation in explaining limitations of traditional particle dissolution expressions demonstrates the usefulness of the general diffusion layer model.     

Random primed polymerase chain reaction differentiates Codonopsis pilosula from different localities

DNA fingerprints distinctive among the samples from different localities in China were successfully reproduced for the Chinese herb Dangshen, the roots of CODONOPSIS PILOSULA, (Campanulaceae). Similarity index (S.I.) analysis revealed that C. PILOSULA samples from the same province generated similar DNA fingerprints, while samples of different provinces displayed different DNA fingerprints. This method may be a general and valuable tool for locality authentication of other Chinese herbal medicinal materials.     

Oxidative bioactivation of the lactol prodrug of a lactone cyclooxygenase-2 inhibitor.

The lactol derivative of a lactone cyclooxygenase-2 inhibitor (DFU) was evaluated in vivo and in vitro for its potential suitability as a prodrug. DFU-lactol was found to be 10 to 20 times more soluble than DFU in a variety of aqueous vehicles. After administration of DFU-lactol at 20 mg kg-1 p.o. in rats, a Cmax of 7.5 microM DFU was reached in the plasma. After oral administration, the ED50s of DFU-lactol in the carrageenan-induced paw edema and lipopolysaccharide-induced pyresis assays in rats are comparable with the ED50s observed when dosing with DFU. Incubations of DFU-lactol with rat and human hepatocytes demonstrated that the oxidation of DFU-lactol can be mediated by liver enzymes and that a competing pathway is direct glucuronidation of the DFU-lactol hydroxyl group. Assays with subcellular fractions from rat liver indicated that most of the oxidation of DFU-lactol occurs in the cytosolic fraction and requires NAD(P)+. Human liver cytosol can also support the oxidation of DFU-lactol to DFU when NAD(P)+ is added to the incubations. Fractionation of human liver cytosolic proteins showed that at least three enzymes are capable of efficiently effecting the oxidation of DFU-lactol to DFU. Incubations with commercially available dehydrogenases suggest that alcohol and hydroxysteroid dehydrogenases are involved in this oxidative process. These data together suggest that lactols may represent useful prodrugs for lactone-containing drugs.     

氟伐他汀对自发性高血压大鼠阻力血管 功能的影响

AIM: To evaluate the effects of fluvastatin, a hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor, on the alterations of structure and function of resistant vessels in spontaneously hypertensive rats (SHR). METHODS: Eight-week-old male SHR were given fluvastatin 20 mg.kg-1.d-1 by gavage. Rats were decapitated at 16 wk. Wall-to-lumen area ratios (W/L) of thoracic aorta and mesenteric arteries (3rd grade branch) were assessed by morphometric assay. The effects of fluvastatin on vascular reactivity to sodium nitroprusside (SNP) and norepinephrine (NE), were studied with rings of thoracic aorta and mesenteric arteries isolated from rats. RESULTS: After 8 wk of treatment, histological examination showed that the wall-to-lumen area ratio was lower in SHRflu than that in SHR (0.44 +/- 0.09 vs 0.79 +/- 0.09, P < 0.05). EC50 of vasodilation response was much lower in SHRflu than that in SHR [(4.9 vs 190) pmol.L-1, P < 0.05], while EC50 of mesenteric artery rings from SHRflu was somewhat lower than that of SHR [(0.02 vs 0.04) nmol.L-1, P > 0.05]. In both aortic and mesenteric artery rings, EC50 of vasoconstriction in response to NE from SHRflu was higher than that of SHR [thoracic aorta: (0.20 vs 0.02) nmol.L-1, P < 0.05; mesentric arteries: (1.46 vs 0.72) nmol.L-1, P < 0.05]. CONCLUSION: Short-term treatment with fluvastatin ameliorated the vasomotoricity of resistant vessels, enhanced the sensitivity to vasodilator and depressed the sensitivity to vasoconstrictor; fluvastatin also attenuated the resistant vascular hypertrophy during the development of hypertension in SHR.     

高效液相色谱—间接光度检测法同时测定血清和尿中5种氨基苷类抗生素

目的：建立一种直接分离测定体液中庆大霉素、丁胺卡那霉素、妥布霉素、西梭霉素和乙基西梭霉素等５种氨基苷类抗生素的高效液相色谱－间接光度检测（ＨＰＬＣ－ＩＰＤ）法。方法：在流动相中加入具有紫外检测响应的检测剂烟酰胺,用紫外检测器直接测定紫外吸收很差的上述５种药物。Ｃ１８固定相,流动相为含烟酰胺０５ｍｍｏｌ·Ｌ－１、庚烷磺酸钠５ｍｍｏｌ·Ｌ－１和磷酸００５ｍｏｌ·Ｌ－１的甲醇－乙腈－水（２７∶１８∶５５）混合溶液。结果：血清和尿样平均回收率均大于９６％,日内和日间ＲＳＤ均小于６％。并测定了肌注此类药物病人的血清和尿样品。结论：该法适于体液中氨基苷类药物检测。     

中药川芎中无机阴离子和有机酸成分的研究

目的：研究中药川芎中有机酸和无机阴离子的同时分析方法。方法：采用非抑制型阴离子交换色谱法,色谱柱为ＳｈｉｍｐａｃｋＩＣＡ１,流动相为０８ｍｍｏｌ·Ｌ－１邻苯二甲酸氢钾。结果：川芎提取液中３种有机酸和３种无机阴离子得到了较好的分离。结论：该方法分析速度快,准确,灵敏度高。     

K-serotype analyses of Vibrio parahaemolyticus isolated in northern Taiwan, 1983 through 1993

From 1983 through 1993, 786 strains of Vibrio parahaemolyticus were collected from food-borne disease outbreaks and sporadic cases of diarrheal illness in northern Taiwan, involving 42 K-serotypes. Five top leading serotypes were K8 (36.8%), K15 (10.8%), K12 (8.7%), K56 (7.9%) and K63 (4.7%). However, a variation of K-serotypes was found during this study period. From 112 food-borne outbreaks associated with this microorganism, only 54 (48.2%) outbreaks were caused by a single serotype, while 58 (51.8%) were caused by multiple K-serotypes. Numbers of outbreaks caused by two, three and more than three K-serotypes were 29 (26%), 16 (14.2%), and 13 (11.6%), respectively. In a special outbreak, eight K-serotypes was found. Outbreaks caused by party caterers were most frequently associated with multiple K-serotypes.     

Clinical and Angiographic Experience with Coronary Stenting Using Freedomª Stent

The immediate safety and efficacy and the 6 month clinical and angiographic follow-up of a new fish-scale designed coronary coil stainless steel stent (Freedoma) was assessed by a prospective study. During 1995, 169 patients were treated on 177 vessels using 233 Freedom stents. Procedural indication for stenting was a bail-out situation in 79 vessels, a suboptimal angioplasty result in 62 vessels and a third restenosis after PTCA in 36 vessels. Procedural success was achieved in 170 vessels (96%); in 162 patients (96%). Subacute thrombotic occlusion occurred in one patient (0.6%). Acute myocardial infarction occurred in 7 patients (4.1%). Bleeding complications, necessitating blood transfusion occurred in 6 patients (3.6%). There were two non-stent related deaths. Recurrence of stent-related angina pectoris and/or a positive stress test occurred in 10 pts (6.4%). Elective control angiography at 6 months was performed in the first 85 patients. Stent restenosis of 3 50% diameter stenosis was found in 14 patients (16.5%).     

Primary intramedullary spinal cord primitive neuroectodermal tumor with intracranial seeding in an infant

Primary spinal cord primitive neuroectodermal tumor (PNET) is a rare entity. In all, 13 cases have been reported in the literature, including 3 with intracranial seeding. A 3-month-old girl with involvement of the spinal cord below the mid-thoracic level is described. The brain MRI revealed findings indicative of seeding along the intracranial subarachnoid space. Biopsy, duraplasty and removal of laminotomy flap were done. In spite of a good response to the first cycle of postoperative 8-drugs-in-a-day chemotherapy, further treatment was refused. She died 21 days after the onset of leg weakness, which reveals the rapid progression of untreated cases. To our knowledge, this is the first case of spinal cord PNET with parenchymal involvement that has been described in an infant.