Long term treatment of severe hypercholesterolaemia with guar gum

The long term efficacy of granulated guar gum, 15-30 g per day, was studied in 23 patients with severe hypercholesterolaemia (serum cholesterol concentration between 8.0 and 14.3 mmol/l). Originally, 29 patients participated in the study. Two patients dropped out because of gastrointestinal side effects, two others were not willing to complete the study without any given reason, and two discontinued the study because of hospitalization. A 1-month placebo period preceded the guar gum treatment, and another 1-month placebo period followed after 50 weeks of active treatment. The serum total cholesterol concentration (mean +/- SEM) was reduced from 10.0 +/- 0.4 mmol/l to 8.2 +/- 0.3 mmol/l (P less than 0.001) after 8 weeks and to 9.0 +/- 0.4 mmol/l (P less than 0.001) after 50 weeks on guar gum. During the second placebo period serum cholesterol returned to the pretreatment level. After 34 weeks of active treatment the serum LDL-cholesterol concentration had fallen by 15% and that of apoprotein B by 14% from the baseline. The changes in lipid and lipoprotein levels were independent of the initial values and the type of hypercholesterolaemia. Serum triglycerides, HDL-cholesterol, body weight and blood pressure showed no significant changes during the trial. Of the study subjects, 20 reached the maximum intended dose of 30 g per day guar gum between 8 and 14 weeks and thereafter 11 subjects continued the dose of 30 g/day while 12 subjects reduced the dose to 15-25 g/day.(ABSTRACT TRUNCATED AT 250 WORDS)     

Design of poly-epsilon-caprolactone nanospheres coated with bioadhesive hyaluronic acid for ocular delivery.

This study was performed to design a new ocular drug delivery system based on poly-epsilon-caprolactone (PCL) biodegradable nanospheres (NS) coated with a bioadhesive polymer, hyaluronic acid (HA), in order to combine ophthalmic prolonged action with the ease of application. The aim of this work was to investigate three strategies to attach HA on NS surface: (1) coating the core by chain entanglement with HA; (2) coating NS by HA adsorption; (3) coating NS by electrostatic interactions between negatively charged HA and a cationic surfactant (stearylamine, SA, or benzalkonium chloride, BKC). A radioimmunoassay technique, usually used for HA quantification in serum, was transposed to determine the amount of HA on the NS. The results show that HA is strongly attached on NS positively charged by cationic surfactant. This system is stable and not influenced by dilution. These results show the possibility of using cationic surfactants to obtain a HA coating by electrostatic interactions. BKC, approved for ophthalmic administration, was retained because it was more firmly anchored within the PCL matrix and the amount of HA attached was high (41.6 microg HA/mg PCL). Moreover, the yield of fixation reached 50%. Therefore, by using a simple preparation method, it was possible to obtain stable HA and intact HA-coated NS.     

Inhibitory effect of zinc oxide on contact allergy due to colophony

Contact allergy to a wound dressing with an adhesive mass consisting of colophony, zinc oxide and rubber (Mezinc) was studied in 179 patients with a history of eczema. 12 patients were found to be allergic to colophony, whereas only 4 of these patients also showed a positive patch test reaction to the wound dressing. 14 patients with verified moderate contact allergy to colophony were patch tested with adhesive mass (10%), Portuguese colophony (10%), zinc oxide (10%), purified resin acids (10%), and Portuguese colophony (10%), in combination with zinc oxide. Only 3 patients reacted to the adhesive mass, whereas all patients showed a positive patch test reaction to Portuguese colophony. A combination of zinc oxide (10%) with Portuguese colophony (10%) provoked a positive patch test reaction in only 5 of these 14 patients. An allergic reaction to abietic acid (90-95% purity) was found in 7 patients and to neoabietic acid (99 + %) in 3 patients, whereas no reactions to dehydroabietic (99 + %), isopimaric (99 + %) or levopimaric acids (98 + %) were found.     

MPEO-PLA nanoparticles: effect of MPEO content on some of their surface properties.

Nanoparticles of poly(lactic acid) (PLA) and of blends of PLA and monomethoxypoly(ethylene oxyde) (MPEO-PLA) were prepared by the double emulsion method. Sucrose was added to overcome nanoparticle aggregation with freeze-drying. Whereas PLA nanoparticles rapidly are phagocytosed by the mononuclear phagocyte system cells, the uptake of MPEO-PLA nanoparticles is delayed. Opsonization is one of the steps of phagocytosis, and serum complement is a major component of the opsonin system. The in vitro complement consumption of the prepared nanoparticles was evaluated as a function of time and of their surface area. To avoid the aggregation of MPEO-PLA nanoparticles due to MPEO crystallization, sucrose was necessary, and its concentration was dependent on MPEO proportion in the nanoparticle suspension. As expected, the complement consumption for PLA nanoparticles is faster and more important than for PLA/MPEO-PLA blends. The complement consumption decreases with the increase in MPEO surface density. Complement is less consumed with the lower surface density provided by a higher molecular weight than by the higher surface density provided by a lower molecular weight MPEO. The complement consumption seems to be dependent on the number of nanoparticles in contact with human serum. Finally, the model of steric repulsion of MPEO towards proteins and the importance of the surface density of MPEO were emphasized.     

GFR determination in adults with a single-sample iohexol plasma clearance method based on the mean sojourn time.

BACKGROUND: Glomerular filtration rate is a key parameter in kidney disease. The Radionuclides in Nephrourology Committee has recommended a single-sample method with 99mTc-DTPA based on the mean sojourn time. This study was done to develop the method for use with iohexol making the method more available. METHODS: The single-sample formula was derived for group I (n = 48, Cl = 8-188 ml/min) and applied on group II (n = 47) and on group III (n = 123). In groups I and II, reference clearance was determined according to Sapirstein and in group III according to Br?chner-Mortensen. RESULTS: The formula Cls= (-b+sqrt b2-4ac)/(2a) (a = (-6.49 x 10(-6) x t + 8.85 x 10(-4)) x t, b = 1.143 x t and c = ln[(C(t))x(ECV/Q0)](ECV) was derived for patients with estimated Cl > 30 ml/min with the best result if the single sample was obtained between 4 and 5 h. Extracellular volume was estimated as ECV =9985 x BSA - 3431. The formula ClS(24 h) = -ln[(C(t)) x (ECV/Q0)](ECV)/(t) was developed for patients with estimated Cl <30 ml/min with a single sample at 24 h. With this combined approach SDdiff was 2.7 ml/min in group II and 3.1 ml/min in group III. CONCLUSIONS: An accurate determination of iohexol clearance can be obtained from a single plasma sample applying the mean sojourn time approach. A separate formula must be used for patients with low clearance values. Body surface area (BSA), injected amount of iohexol (Q0), time when the single sample is drawn (t) and the concentration of iohexol [C(t)] in the sample are needed for the calculations.     

Serum beta-carotene before and after beta-carotene supplementation.

A two-month double-blind, placebo-controlled supplementation study of oral beta-carotene (20 mg daily) was conducted. Two hundred and twenty two 30-69 year old men were randomized into either a beta-carotene or placebo group, and serum samples were obtained at baseline, follow-up (2 months), and up to 12 weeks post-supplementation. Serum beta-carotene increased on average 10-fold in the beta-carotene group, from 0.53 +/- 0.32 mumol/l (mean +/- SD) at baseline to 4.99 +/- 2.47 mumol/l at follow-up (P less than 0.0001), and beta-carotene levels remained elevated up to 12 weeks post-supplementation (0.61 +/- 0.15 mumol/l). No changes in serum retinol, alpha-tocopherol, or total cholesterol were observed. At baseline, serum beta-carotene levels were positively correlated with dietary beta-carotene (r = 0.29) and inversely correlated with body mass index and serum gamma-glutamyltransferase (r = -0.33 and r = -0.40, respectively). The inverse association with body mass index and serum gamma-glutamyltransferase persisted during active supplementation, whereas the positive association with dietary beta-carotene disappeared. In multivariate analysis, serum cholesterol was also positively associated with serum beta-carotene levels both before and after supplementation. Baseline serum beta-carotene was the factor most strongly associated (positively) with serum beta-carotene after supplementation. Our study highlights the importance of several factors which affect serum beta-carotene.     

Relationship between complement activation, cellular uptake and surface physicochemical aspects of novel PEG-modified nanocapsules

The aim of our work was to examine the relationship between modifications of the surface of nanocapsules (NC) by adsorption or covalent grafting of poly(ethylene oxide) (PEG), and changes in their phospholipid (PL) content on complement activation (C3 cleavage) and on uptake by macrophages. The physicochemical characterization of the NC included an investigation of their properties, such as surface charge, size, hydrophilicity, morphology and homogeneity. This is the first time that such properties have been correlated with biological interactions for NC, a novel carrier system with a structure more complex than nanospheres. C3 crossed immunoelectrophoresis revealed the reduced activation for NC with longer PEG chain and higher density, although all formulations induced C3 cleavage to a lesser or greater extent. NC bearing PEG covalently bound to the surface were weaker activators of complement than plain PLA [poly(D,L-lactide)] NC or nanospheres (NS). Furthermore, the fluorescent/confocal microscopy of J774A1 cells in contact with NC reveal a dramatically reduced interaction with PEG-bearing NC. However, the way in which PEG was attached (covalent or adsorbed) seemed to affect the mechanism of uptake. Taken together, these results suggest that the low level of protein binding to NC covered with a high density of 20kDa PEG chains is likely to be due to the steric barriers surrounding these particles, which prevents protein adsorption and reduces their interaction with macrophages.     

Serum amyloid A protein, apolipoprotein A-I, and apolipoprotein B during the course of acute myocardial infarction.

Serum amyloid A protein (SAA), apolipoprotein A-I (apoA-I), apolipoprotein B (apoB) concentrations, and creatine kinase (CK)-MB isoenzyme activity were serially measured in 10 patients during the course of acute myocardial infarction. Pronounced increases in SAA concentrations were observed in all patients during infarction. The highest SAA values were observed, on average, 67 hours after the onset of chest pain. After infarction both apoA-I and apoB concentrations decreased. The reduction in apoA-I concentration 67 to 72 hours after the onset of chest pain was (31%) (p less than 0.01) and the reduction in apoB concentration 55 to 60 hours after the onset of pain was (34%) (p less than 0.01). Negative correlations were found between the concentrations of SAA and apoproteins A-I and B; this inverse relation was stronger between SAA and apoB than between SAA and apo-AI.