Molecular Description of Familial Defective APOB-100 in Malaysia

Familial ligand-defective apolipoprotein B-100 is characterized by elevated plasma low-density lipoprotein levels and premature heart disease. This study aims to determine apolipoprotein B gene mutations among Malaysians with clinical diagnoses of familial hypercholesterolemia and to compare the phenotype of patients with apolipoprotein B gene mutations to those with a low-density lipoprotein receptor gene mutation. A group of 164 patients with a clinical diagnosis of familial hypercholesterolemia was analyzed. Amplicons in exon 26 and exon 29 of the apolipoprotein B gene were screened for genetic variants using denaturing gradient high-performance liquid chromatography; 10 variants were identified. Five novel mutations were detected (p.Gln2485Arg, p.Thr3526Ala, p.Glu3666Lys, p.Tyr4343CysfsX221, and p.Arg4297His). Those with familial defective apolipoprotein had a less severe phenotype than those with familial hypercholesterolemia. An apolipoprotein gene defect is present among Malaysian familial hypercholesterolemics. Those with both mutations show a more severe phenotype than those with one gene defect.     

Current Concepts in Intestinal Peptide Absorption

Today there is considerable interest in oral peptide delivery. However, oral administration of peptides is limited by a low bioavailability and a high variability in plasma levels. A review is given of the literature describing the major barriers in peptide absorption, the basic mechanisms of intestinal peptide transport, the experimental models and the pharmaceutical approaches currently used in the investigation of peptide and protein absorption processes.     

Absorption of Phosphate and Potassium Ions in Poplar Stems

Phosphate and potassium ions were drawn through segments ofpoplar stem using a vacuum. Analysis of the activity-time curvesfor selected points along the stem were consistent with a mathematicalmodel of mass flow combined with irreversible lateral flow alongthe conducting vessels. However, the phosphate ion could beflushed out of the stems with water, so that it was necessaryto consider this as a limiting case of a reversible-flow model.Comparison is made with the activity-time curves for ion absorptioninto plant tissue, which are considered similar in shape. Avalue of 50 µm min^–1 was obtained for the lateralvelocity, and the ratio of tracer lost laterally to tracer movingon along the pipe was calculated to be about 0.7     

Hypophosphataemia and Hyperphosphataemia in a Hospital Population

One hundred cases of hypophosphataemia (≤ 2·0 mg/100 ml) and 84 cases of hyperphosphataemia (≥ 5·0 mg/100 ml) occurring in a hospital population were studied in order to determine the cause of the abnormality. Examples of hyperphosphataemia due to renal failure were excluded from the study.A low serum phosphorus concentration was most frequently due to intravenous administration of carbohydrate, usually glucose, which accounted for 40% of cases. The next commonest cause was vomiting (12%). No obvious explanation could be found in 26% of cases, but in most of these factors were present which are known to affect phosphorus metabolism.No one cause of hyperphosphataemia was outstanding in frequency and in over 50% of cases no definite explanation for the abnormality could be found.     

Isolation and Characterization of the Enterobacter cloacae cheR Mutant Defective in Phosphate Taxis

A chemotaxis-defective mutant of Enterobacter cloacae IFO3320, designated EC1, was isolated after N-methyl-N'-nitro-N-nitrosoguanidine (NTG) mutagenesis. Computer-assisted capillary assays showed that EC1 failed to show chemotactic responses to peptone and inorganic phosphate (P_i). Cloning and sequence analysis showed that EC1 is a cheR mutant, suggesting that P_i taxis by E. cloacae is dependent on a methyl-accepting chemotaxis protein(s)(MCP). EC1 was further mutagenized with NTG to construct cheR pstS and cheR pstA double mutants. A recombinant plasmid pECT01.2, which contained the E. cloacae cheR gene, restored the ability of these double mutants to show chemotaxis toward peptone but not P_i. These results suggest that the phosphate-specific transport (Pst) system, together with a MCP(s), is required for detecting P_i in E. cloacae.     

长春新碱阳离子纳米结构脂质载体及其小肠吸收的研究

目的:硫酸长春新碱作为一种细胞毒型抗肿瘤药物,临床上多用其注射剂,虽应用广泛,但存在较多缺点,如药物半衰期短,代谢速率快以及毒副作用明显。本文目的是制备包载长春新碱和十二烷基磺酸钠的阳离子纳米结构脂质载体,并对其进行评价。方法:用复乳挥发法制备出目标脂质纳米粒;利用激光粒度仪对其粒径及zeta电位进行检测;利用高效液相色谱法对其包封率和载药量进行测定;透析法检测纳米粒的体外释放行为;用小肠吸收法评价纳米粒的促进吸收作用。结果:制得的纳米粒的平均粒径为(192.4±4.14)nm,多分散系数(PDI)为0.184±0.015,包封率为32.28%,Zeta电位为(30.6±4.09)m V,载药量为(1.56±0.10)%;体外释放实验显示在pH=7.4的中性释放介质中,硫酸长春新碱脂质纳米粒表现出缓释特性;小肠吸收实验表明十二烷基磺酸钠的加入和阳离子纳米粒的修饰可提高小肠对药物的吸收。结论:阳离子硫酸长春新碱纳米结构脂质载体具有缓释效果,并可以促进小肠对药物的吸收。     

Arterial Oxygen Desaturation and Intestinal Absorption of Xylose

Small-bowel absorption was studied using the xylose absorption test in 16 patients with varying degrees of arterial oxygen desaturation due to either congenital heart disease or chronic lung disease. Xylose absorption was decreased in the cases with more severe desaturation. The correlation of xylose absorption with arterial saturation was significant. In nine cases hypoxia was relieved by either oxygen administration or surgery. Repeat testing showed an increase in xylose absorption in every case, the mean increase being 11·7%, which was statistically significant.     

Studies on Inhibition of Intestinal Absorption of Radioactive Strontium: I. Prevention of Absorption from Ligated Intestinal Segments

A method is reported which permits selective suppression of absorption of radioactive strontium from ingested food material, permitting the calcium to be available to the body. Studies were carried out in vivo by injection of Sr⁸⁹ and Ca⁴⁵ in the presence of inert carrier into ligated intestinal segments in rats, and the amount of absorption was measured by standard monitoring techniques. The pattern of absorption of both ions is very similar but the rate of absorption is different. It was found that the polyelectrolyte, sodium alginate, obtained from brown algae (Phaeophyceae), injected simultaneously with radiostrontium effectively reduces the absortion of Sr⁸⁹ from all segments of the intestine by as much as 50-80% of the control values. No significant reduction in absorption of Ca⁴⁵ was observed in equivalent concentrations. The reduction in blood levels of Sr⁸⁹ and in bone uptake corresponded to the absorption pattern. The difference in the effect on strontium and calcium absorption may be due to differences in the binding capacity of sodium alginate from the two metal ions under the conditions present in vivo.     

Hypophosphataemia after parathyroidectomy in chronic renal failure.

Out of 24 patients receiving haemodialysis who were subjected to parathyroidectomy, 13 developed hypophosphataemia; this persisted for 3-52 weeks (mean 10.6 weeks). Before operation these 13 patients had had significantly higher plasma alkaline phosphatase activities (p less than 0.01) and significantly higher values in iliac crest bone biopsy samples for active resorption surface and active formation surface (p less than 0.05 in each case) than the group who remained normophosphataemic. Significantly more of the patients who remained normophosphataemic had shown periarticular calcification in preoperative skeletal radiographs (p less than 0.001). Hypophosphataemia may result from reduced mobilisation of phosphate from bone or its increased accretion into bone, and resorption of phosphate from periarticular mineral deposits may protect against development.     

Intestinal Scavenger Receptors Are Involved in Vitamin K1 Absorption

Vitamin K₁ (phylloquinone) intestinal absorption is thought to be mediated by a carrier protein that still remains to be identified. Apical transport of vitamin K₁ was examined using Caco-2 TC-7 cell monolayers as a model of human intestinal epithelium and in transfected HEK cells. Phylloquinone uptake was then measured ex vivo using mouse intestinal explants. Finally, vitamin K₁ absorption was compared between wild-type mice and mice overexpressing scavenger receptor class B type I (SR-BI) in the intestine and mice deficient in cluster determinant 36 (CD36). Phylloquinone uptake by Caco-2 cells was saturable and was significantly impaired by co-incubation with α-tocopherol (and vice versa). Anti-human SR-BI antibodies and BLT1 (a chemical inhibitor of lipid transport via SR-BI) blocked up to 85% of vitamin K₁ uptake. BLT1 also decreased phylloquinone apical efflux by ∼80%. Transfection of HEK cells with SR-BI and CD36 significantly enhanced vitamin K₁ uptake, which was subsequently decreased by the addition of BLT1 or sulfo-N-succinimidyl oleate (CD36 inhibitor), respectively. Similar results were obtained in mouse intestinal explants. In vivo, the phylloquinone postprandial response was significantly higher, and the proximal intestine mucosa phylloquinone content 4 h after gavage was increased in mice overexpressing SR-BI compared with controls. Phylloquinone postprandial response was also significantly increased in CD36-deficient mice compared with wild-type mice, but their vitamin K₁ intestinal content remained unchanged. Overall, the present data demonstrate for the first time that intestinal scavenger receptors participate in the absorption of dietary phylloquinone.