The effect of growth retardation and of osteomalacia on the uptake of albumin by bone

Summary ¹²⁵I-labeled rat albumin injected intravenously into rats was taken up by growing bone. Some of this radioactive albumin could be removed from bone by washing with saline, the proportion so removed decreasing from 82.5% at 1 day to 7.4% at 8 days. Both the total radioactivity, and that remaining in bone after saline wash, were reduced when growth was slowed by alteration or restriction of the diet. Although the amount of¹²⁵I albumin in rachitic bone was reduced, autoradiography showed that radioactivity was present in rachitic osteoid. Immunoprecipitation using anti-rat-albumin serum showed that about half of the radioactivity released from normal bone by EDTA was still attached to albumin. These results suggest that albumin plays some part in the growth of bone.Part of this work was presented at a meeting of the Australian Physiological and Pharmacological Society in May 1974     

Modifications of the cerebrospinal fluid IgG concentrations in patients with multiple sclerosis treated with intrathecal steroids

Summary Forty-one patients with multiple sclerosis (MS), in the acute exacerbation phase of the disease, were treated with three or four intrathecal injections of triamcinolone retard, 40 mg. Cerebrospinal fluid (CSF) specimens were collected at the first and at the last lumbar puncture, and analyzed for IgG and albumin. There was a decrease of CSF IgG concentration in the specimens of 85% of the cases which were collected at the last lumbar puncture, compared to the initial concentration. Similarly, the CSF IgG/albumin ratio in the last specimens collected were reduced in 78% of the cases. Both these results are statistically significant.Presented to the Meeting of Swiss Neuropathologists with International Participation, St. Moritz, 6 to 9 March 1978     

Influence of smoking on metallothionein level and other proteins binding essential metals in human milk

Aim: To assess the influence of smoking on the level of total protein, metallothionein (MT), albumin and lactoferrin in human breast milk. Methods: Samples of whole milk and supernatants of milk after centrifugation at 10 000×g and 105 000×g were analysed. Cadmium was determined by graphite furnace atomic absorption spectrometry (GFAAS). The concentration measurements employed the following methods: total protein by Lowry, albumin by colorimetry, cotinine and lactoferrin by ELISA tests, metallothionein by ¹⁰⁹Cd/haemoglobin assay. Results: The assessment of tobacco smoke exposure was based on concentrations of cotinine in breast milk (197±98 ng/ml in smokers and 23±11 ng/ml in non-smokers; p≤0.001) and serum (179±87 ng/ml and 32±19 ng/ml, respectively; p≤0.001). The level of cadmium was four times higher in the milk of smoking women than in non-smokers. The concentration of total protein was lower in smoking (37.3±10.6 mg/ml) than in non-smoking mothers (51.8±13.8 mg/ml; p≤0.02). No significant differences between albumin and lactoferrin concentrations were observed. The level of metallothionein was over twice as low in smokers (5.1±1.9 μg/ml) than in non-smokers (13.4±3.0 μg/ml; p≤0.001), and an inverse correlation between MT level and cadmium concentration (r=-0.86; p=0.001) was noticed.

Conclusions: The breast milk of smoking mothers might be of lower nutritive value. The amount of MT transported by milk to the mammary gland is smaller in smokers than in non-smokers, which may prove to be advantageous to an infant because of the higher toxicity of the Cd-MT complex than that of inorganic Cd salts.     

Development of a scaled up liver device incorporating cryo-preserved pig liver micro-organs

BACKGROUND/AIMS: Currently there is no effective therapy for most patients with fulminant or end stage liver disease. METHODS: Pig liver micro-organs (LMOs), which preserve liver micro-architecture and ensure a maximal 150-200mum distance from a source of nutrients and gases have been prepared and a method to cryo-preserve them has been developed. A new scaled-up extra-corporeal liver device termed aLIVE-H in which LMOs are exposed to liver-like hemodynamic conditions has also been developed. The purpose of this work is to test the safety and function of cryo-preserved LMOs and how the hemodynamic properties of the scaled up aLIVE device affect their function. RESULTS: Pig LMOs in aLIVE-H, transcribe albumin and Factor V at similar levels, irrespective of their position within the bioreactor, indicating that the hemodynamic features of the aLIVE-H device allow for homogeneous plasma distribution and proper function at different locations. Cryo-preserved LMOs transcribe albumin and Factor V at levels comparable to those transcribed by a normal pig liver. Connecting the aLIVE-H bioreactor to normal pigs did not affect key blood components and biochemical parameters. CONCLUSIONS: An extra-corporeal liver device aLIVE-H which imitates the hemodynamic and functional properties of the normal liver and incorporates cryo-preserved LMOs has been developed and characterized. aLIVE-H was found to perform key synthetic liver functions.     

Bisalbuminemia in chronic kidney disease

Hereditary and acquired bisalbuminemia, in which the serum contains an albumin variant differing from albumin A by single amino-acid substitutions, have been reported in different races or ethnic groups and in association with various pathologic states. The importance of this rare condition in the pathophysiology of established diseases is uncertain. We evaluated a 68-year-old woman with chronic kidney disease who presented with worsened serum creatinine concentration despite lack of dietary or medical changes. Serum protein electrophoresis was performed with an automated rapid electrophoresis system. Bisalbuminemia was noted as an incidental finding on serum protein electrophoresis. The serum creatinine level stabilized with dietary protein restriction and a -blocking agent/diuretic combination for blood pressure control. Although the possibility that some physiologic or pharmacologic substances may not bind to abnormal albumin variants as well as they bind to normal albumin should not be discounted, the finding of bisalbuminemia did not influence the diagnosis, management, course, or prognosis of chronic kidney disease. The role of persistent bisalbuminemia in renal disease is uncertain.     

Albumin-coated tympanostomy tubes: prospective, double-blind clinical study

OBJECTIVES: Coating an implant with albumin prevents adhesion of proteins, bacteria, and platelets and thus may lead to its improved and prolonged function. Previously, we have demonstrated the inhibition of binding of fibronectin, one of the most adhesive glycoproteins, on human serum albumin (HSA)-coated tympanostomy tubes and the durability of this binding inhibition in a 8-month trial. We have also demonstrated that the HSA coating inhibits the binding of Staphylococcus aureus and Pseudomonas aeruginosa to titanium plates. This prospective study evaluated the effect of albumin coating on tympanostomy tube sequelae and on the outcome of tympanostomized patients. STUDY DESIGN: Double-blind, prospective, randomized clinical trial. METHODS: Two otolaryngological centers in southern Finland enrolled 179 pediatric patients. Number of tube occlusions and otorrhea and tube ventilation time in the ears with HSA-coated titanium tympanostomy tubes were compared with the contralateral ear with its uncoated, otherwise identical titanium tube during a 9-month follow-up period. RESULTS: In HSA-coated tubes, average ventilation time was slightly longer and the number of early tube occlusions significantly less (P < .05). Moreover, in patients with perioperative bleeding, the coating prolonged average ventilation time of tympanostomy tubes significantly (P < .05). CONCLUSIONS: HSA coating reduces early tube occlusions by preventing adherence of blood and secretion.     

Altered pharmacokinetics and liver targetability of methotrexate by conjugation with lactosylated albumins

Toenhance the liver targetability, methotrexate (MTX) was conjugated with albumin previously substituted with varying content of lactose (L₀, L₅, and L₂₄). The uptake of MTX by rat hepatocytes in vitro increased according to the increase in the lactose content on the albumin conjugates. The MTX level in the plasma and various organs was determined by counting the radioactivity of [³H]MTX and by HPLC assay, separately, to monitor the in vivo fate of MTX not only as total, regardless of forms of MTX, but also as free/intact MTX level. Conjugation of MTX with albumin alone provided the enhanced delivery of MTX to the liver, accompanied by decreased accumulation in the kidney, but by increased accumulation in other nontarget organs such lung, heart, and spleen. Lactosylation of albumin conjugates further enhanced the delivery of MTX to the liver in a lactose content-dependent manner, accompanied by decreased accumulation of MTX in the lung and heart as well as kidney. The total MTX level accumulated in the liver was 2.9-, 4.1-, and 11.0-fold higher at 1 h and 5.4-, 7.0-, and 16.5-fold higher at 4 h after injection of MTX-L₀, L₅, L₂₄ albumin conjugates compared with MTX alone. MTX conjugates with lactosylated albumin provided low but prolonged level of free/intact MTX in the liver. Taken together, the pharmacokinetics and liver targetability of MTX could be favorably modulated by controlling the lactose content on the albumin conjugates. Lactosylated albumin conjugation might also provide prolonged and targeted delivery of other drugs for the treatment of liver diseases.     

Improvement of metabolic performance of cultured hepatocytes by high oxygen tension in the atmosphere

Maintaining metabolic functions of cultured hepatocytes at higher levels is an essential requirement for the development of a bioartificial liver. We investigated the effect of oxygen tension (10--40%) of the medium on immobilization efficiency and metabolic functions of cultured hepatocytes obtained from a rat for up to 4 days. Immobilization efficiencies of cultures in 10% oxygen showed a significantly lower value from those for the other conditions. The ammonium metabolic rate and the albumin secretion rate were significantly improved with an increase of dissolved oxygen tension for up to 2 days. These values remained similar in the later stage of the culture. The urea secretion rate showed similar values in all conditions. In conclusion, higher oxygen tension improved immobilization efficiency and metabolic functions of cultured rat hepatocytes in the earlier stage of culture for up to 2 days.     

Induction of secretion and surface capping of microneme proteins in Eimeria tenella

Micronemes are secretory organelles of the invasive stages of apicomplexan parasites and contain proteins that are important for parasite motility and host cell invasion. We have examined the induction of microneme secretion in the coccidian Eimeria tenella. When sporozoites were added to MDBK cells in culture, microneme proteins were secreted, capped backwards over the parasite surface and deposited onto underlying host cells from the posterior end of gliding parasites. Induction of secretion was also achieved by the addition of foetal calf serum, or purified albumin, to extracellular sporozoites. Microneme secretion per se was not dependent on parasites being able to move or to invade host cells. However, in the presence of cytochalasin D, which disrupts actin polymerisation and prevents parasite movement, microneme proteins were secreted from the apical tip but were not capped backwards over the sporozoite surface. These observations support the hypothesis that microneme proteins function as ligands which, when secreted out onto the parasite surface, form a link, either directly or indirectly, between the sub-pellicular actin–myosin cytoskeletal motor of the parasite and the surface of target host cells.     

肾病综合征管周毛细血管网改变的致病作用

目的研究肾小管周毛细血管网在肾病综合征中的改变,探讨间质微血管系统改变在肾病综合征患者间质纤维化过程中的可能性致病作用。方法采用免疫组化SP法,在蛋白质水平检测72例肾组织标本(肾病综合征组50例,对照组22例)肾小管上白蛋白沉积,同时观察肾小管周毛细血管组织学和形态学的改变以及分析肾组织纤维化程度。结果与对照组比较,肾小管周毛细血管分布密度,管腔开放程度与白蛋白的沉积之间有显著的负相关(r=-0.861,r=-0.865,r=-0.869,P<0.01);肾小管间质纤维化与肾小管周毛细血管分布密度,血管腔面积亦呈显著性负相关(r=-0.959,r=-0.770,r=-0.907,P<0.01)。结论在肾病综合征中,肾小管刷状缘白蛋白重吸收增加,可能是导致肾小管周微血管网密度降低,血管闭塞程度增加,促使肾间质纤维化发生、发展的关键因素之一。