Comparison of the Permeability Characteristics of a Human Colonic Epithelial (Caco-2) Cell Line to Colon of Rabbit,Monkey, and Dog Intestine and Human Drug Absorption

The in vitro permeabilities of Caco-2 monolayers and permeabilities in tissue sections from colon of monkey, rabbit, and dog were compared using a series of compounds. The selected compounds differed in their physicochemical properties, such as octanol/water partition coefficient, water solubility, and molecular weight. Their structure included steroids, carboxylic acids, xanthins, alcohols, and polyethylene glycols. A linear permeability relationship was established between Caco-2 and colon tissue from both rabbit and monkey. The results suggest that Caco-2 is twice as permeable as rabbit and five times as permeable as monkey colon. However, no clear relationship could be established between Caco-2 monolayers and dog colon permeability. A relationship between permeability in Caco-2 monolayers and human absorption was found. The results suggest that within certain limits, permeability of Caco-2 monolayers may be used as a predictive tool to estimate human drug absorption.     

心脏连续横断断层的解剖学研究

用20个成人尸体心脏,从右心耳上缘平面向下作1.0cm厚的连续横断断层切片。对心脏每一断层下断面,进行各项观测,同时还观察了心脏各断层与胸壁的对应关系。     

胸腰段骨折术后内固定断裂及松动的原因分析

目的探讨脊柱胸腰段骨折内固定术后,内固定物断裂及松动的原因与对策。方法1999年4月至2006年9月期间,采用内固定手术治疗287例胸腰段骨折患者,其中T10 12例,T11 24例,T12 40例,L1 125例,L2 48例,L3 26例,L4 12例。结果17例患者发内固定物断裂,其中12例椎弓根螺钉断裂,2例螺钉松动,2例固定棒断裂,1例连接杆断裂。结论针对患者的具体情况选用合适的内固定器材,术中充分植骨,尽早取出内固定材料以及术后常规进行外固定能有效的防止椎弓根内固定物的断裂。一旦发生内固定物的断裂应该根据具体情况进行处理,可获得较好的预后。     

Completion of the Four Large Gene Sequences of Porcine Group C Cowden Rotavirus

The terminal nucleotide sequences of group C Cowden rotavirus gene segments 1-4 were determined. When compared with the published sequences, we found 14 to 29 additional nt at the 5 ends of the four reported gene sequences. For the 3 ends, we observed an additional 16 nt in gene 2 and 14 fewer nt in gene 4.     

Sites of arginine synthesis and urea production along the nephron of a desert rodent species,Meriones shawi

The distribution of arginine synthase and arginase activities along the successive nephron segments ofMeriones kidney was measured in vitro with single tubule enzymatic microtechniques making use of eitherl-[ureido-¹⁴C] Citrulline (0.108 mM) orl-[guanidion-¹⁴C]arginine (0.2 mM) as the respective substrates. Arginase activity (fmol urea formed per min per mm of tubule) was very low (5–25 fmol.min^–1.mm^–1) in most nephron segments including the early portions of proximal convoluted tubules (early PCT). It increased progressively after 3 mm of the PCT to reach a value of 200 fmol.min^–1.mm^–1 in the cortical portion of the straight proximal tubule (CPST), with a further increase, along the pars recta, of up to 250 fmol.min^–1.mm^–1 in the outer medullary portion (OSPST). In addition, arginase activity in OSPST and the adjacent descending thin limb (DTL) was higher in juxtamedullary nephrons (JN) than in the corresponding portions of superficial nephrons (SN). Arginine synthase activity (fmol arginine formed per mm of tubule per min) was present in proximal tubules exclusively, with a gradient decreasing along the PCT (about 600 fmol.min^–1.mm^–1 in the 1st mm, 65 fmol.min^–1.mm^–1 in CPST and 30 fmol. min^–1. mm^–1 in OSPST). It has been checked that CPST and OSPST (where the two enzyme systems are present) are able to convert citrulline directly into urea with a yield of 65%. It is suggested that: (1) in early PCT cells, arginine synthase activity permits the conversion of the reabsorbed citrulline into arginine (which then diffuses towards blood vessels); and (2) in pars recta cells, arginase activity results in a net entry of arginine across the basolateral membranes and in a net exit of the formed urea into the tubular fluid, if the permeability to urea of luminal membranes is greater than that of basolateral membranes. Such a mechanism of urea secretion might contribute to the maintenance of urea recycling in the medulla and, thereby, participate in the process of concentrating the urine.     

Synthesis of polyetherurethanes containing L-serine dipeptide and their use as materials for biomedical films

Prepolymers, which were produced by the polyaddition reaction of polytetramethylene glycol (PTMG) or polyethylene glycol (PEG) and 4,4'-diphenylmethane diisocyanate (MDI) or hexamethylene diisocyanate (HMDI), were chain-extended with a linear dipeptide of L-serine (Z-Ser-Ser-OMe) or a cyclic dipeptide of L-serine [c-(Ser)2] to yield novel polyetherurethanes containing dipeptide segments. The relationship between the surface morphology and the biomedical properties of the film of the novel polyetherurethanes was investigated. The surface of PU(PTMG,Z-Ser-Ser-OMe,MDI) film was smooth, but fibrous structures were developed in the bulk of the film with increasing molecular weight of the PTMG segment. The antithrombogenicity of the film containing the low molecular weight PTMG segment was better than that of the usual polyetherurethane film without the dipeptide segments. The partial hydrolysis of the ester groups involved in the dipeptide segment improved the antithrombogenicity. In the surface and the bulk of PU[PTMG,c-(Ser)2,MDI] film, spherulite structures were developed when the molecular weight of the PTMG segment was high, while single crystals with a length of 3-4 microns were produced when the molecular weight of the PTMG segment was low. The antithrombogenicity of the film containing the high molecular weight PTMG segment was better than that of the usual polyetherurethane film without the dipeptide segments. PU(PTMG/PEG,Z-Ser-Ser-OMe,MDI) film and PU[PTMG/PEG,c-(Ser)2,MDI] film were permeated by uraemic toxins. The permeation was accelerated with increasing water content of the film and decreasing molecular weight of the solute. The oxygen permeability of the film of the polyetherurethane containing the linear or cyclic dipeptide segments was greater than that of polyetherurethane film which does not contain the dipeptide segments.     

Anatomic and physiologic development of the photoreceptor of the kitten

Summary The postnatal development of the photoreceptor of the cat was studied using physiological and anatomical methods. The late receptor potential (LRP) was recorded in vitro and the threshold and maximum amplitude determined. The same specimens used in the electrophysiological studies were then prepared for microscopy, and rod cell outer and inner segment length and diameter, photoreceptor density, and inter-receptor distance were determined. A small LRP was first recorded at 9–10 days, but only at very high stimulus intensities. Thereafter, there was a rapid decrease in the threshold and an increase in the amplitude of the LRP. The threshold reached adult values at 17–18 days, while the amplitude of the LRP was adultlike at 23–26 days. Of the anatomical parameters examined, inter-receptor spacing and rod cell diameters seem to be most clearly associated, respectively, with the attainment of adult LRP threshold and amplitude. Outer segment length was adult-like at 35–43 days of age and thus postdated physiological maturity of the photoreceptor. These observations suggest that the surface area of the rod cell outer segment tips is more critical in the development of the adult LRP than is the number of discs in the outer segment. In addition, changes over time in the mean diameter and length of rod cell inner segments follows the pattern of ontogenetic changes in LRP amplitude. These findings imply a close relationship during ontogeny between the metabolic functions of the inner segment and phototransduction at the outer segment disc.This study was supported by the Florida Lions Eye Bank (GST) and by a grant, 2-RO1-EY00376-08, from the National Eye Institute, National Institutes of Health, Bethesda, Maryland (DIH)Andrew Labbie and Joseph Muroff were participants in the Community Laboratory Research Programm sponsored by the Dade County Public School System, Miami, Florida     

Proportional analysis of the kidney arterial segments

Summary The proportional area of each renal arterial segment was analyzed in 49 polyester resin corrosion endocasts of the renal vasculature. We defined a segmental artery as a primary or secondary branch of the renal artery that could be isolated outside the hilum. We found kidneys with five arterial segments in 30 of 49 casts (61.2% of cases) and kidneys with four arterial segments in 19 of 49 casts (38.8%). To enable the evaluation of the proportional areas of the autonomous segments (by using the point-counting planimetry method), each arterial segmental branch was injected with different-colored resin. The superior segment (apical) was present in 36 of 49 casts (73.5% of cases) and had a median proportional area of 13.02%. The anterosuperior and anteroinferior segments were present in 30 of 40 casts (61.2% of cases) and had median proportional areas of 21.36% and 17.18%, respectively. The anterior segment was present in 19 of 49 casts (38.8% of cases; when the mid-kidney anterior surface received only one segmental artery) and had a median proportional area of 28.44%. The inferior segment was present in 100% of cases and had a median proportional area of 22.65%. The posterior segment was also present in 100% of cases and was the segment with the greatest median proportional area (33.76%).     

The interactions of phenytoin and its binding site in DI‐S6 segment of Na+ channel voltage‐gated peptide by NMR spectroscopy and molecular modeling study

Abstract: Nuclear magnetic resonance (NMR) spectra of a model peptide (BL‐DIS6), in the presence of anticonvulsant diphenyl drug, phenytoin (DPH), were measured to obtain the interactions between the selected drug and the model peptide. BL‐DIS6's sequence corresponds to the S6 segment in domain I of rat brain type IIA Na⁺‐channel. NMR studies have demonstrated that the magnitude of the chemical shifts of amide‐ and α‐protons can be used as a measurement of the complex stability and binding site of the peptide. Our NMR results propose a 3₁₀‐helical structure for BL‐DIS6, and suggest a binding cavity for DPH that involves the hydrophobic particles of residues Ans‐7, Leu‐8, Val‐11, and Val‐12. Furthermore, molecular modeling was performed to provide a possible complex conformation that the phenyl portion of DPH is accommodated in the proximity of the C‐terminal residues Ala‐11 and Val‐12, and simultaneously the heterocyclic amine ring of DPH is perching at the residue Asn‐7 periphery and stabilizing the phenyl portion deep insertion into the peptide.