Influence of Size, Dosage, and Surface Structure on Clearance and Tissue Distribution of Intravenous Microspheres

Intravenously injected polystyrene microspheres with functional amino groups (AP-MSs, 0.2,1.0, and 4.0 urn in diameter) were cleared from the blood very rapidly. The calculated half-lives for 0.2-, 1.0-, and 4.0-μm AP-MSs were about 55,60, and 50s; no significant differences were found with 10⁶,10⁷, and 10⁸ microspheres/rat. Loading experiments showed that the liver, spleen, lung, kidney, and heart had a very high capacity to take up AP-MSs. The AP-MSs were distributed mainly to the liver, lung, and spleen, whereas other organs contained less than 1 % of injected AP-MSs. In terms of numbers of AP-MSs per gram of tissue, the highest contents were found in spleen, liver, and lung for 0.2-, 1.0-, and 4.0-um AP-MSs, respectively. There was indication of redistribution of particles from one organ to another during the first 6 h after injection. Chondroitin sulfate A (Chon) and hyaluronic acid (Hya) adsorbed or covalently linked to AP-MSs increased uptake in the liver, with Chon AP-MSs (adsorbed or linked) showing the best effect: about 25% increase compared with unadsorbed 1-μm AP-MSs. Experiments with separated cells in vitro demonstrated that 1 um AP-MSs, intravenously injected, associated only with Kupffer cells. When the microspheres were adsorbed with Chon, there was also association with liver endothelial cells. This finding indicates that conjugation of microspheres with ligands for endothelial receptors may be a useful method for directing microspheres to specific organs, even if the receptors are not by themselves phagocytic     

Diffusive-convective mass transfer rates for solutes present on both sides of a dialyzer membrane

The transport (J) of waste products across dialyzer membranes is known to be proportional to the blood inlet concentration (Cbi) according to J = KCbi, where K is the clearance. For solutes present on both sides of the membrane, like sodium chloride, it has been shown that under certain conditions the transport rate will depend linearly also upon the dialysis fluid inlet concentration Cdi according to J = KbCbi -KdCdi. Kb and Kd are generalized clearances, which depend upon flow rates and membrane permeability but are independent of the concentrations. We have extended the results of Ross et al. in three ways. First, they only considered ultrafiltration (UF) that is equally distributed along the dialyzer. This is an unrealistic assumption, especially in hemodiafiltration and hemofiltration treatments with large UF rates (Quf) leading to large pressure drops along the dialyzer. Our approach allows for an arbitrary UF distribution. Second, it was possible to incorporate the more realistic model of Villaroel et al. for the local combination of diffusion and convection. Finally, we allow an arbitrary distribution of blood among the different fibers. All of these results are valid in both cocurrent and countercurrent configurations. With a sieving coefficient of 1, a good approximation for small solutes, we were also able to show that Kd = Kb - Quf, irrespective of the UF distribution along the dialyzer. This is an important result that, for example, provides a theoretical foundation for allowing a nonzero Quf in conductivity based clearance measurements.     

Exploratory Efficacy of Calcium-Vitamin D Milk Fortification and Periodontal Therapy on Maternal Oral Health and Metabolic and Inflammatory Profile

In this 2 × 2 factorial, outcome-assessor blinded, feasibility randomised trial we explored the effect of a non-pharmaceutical multi-component intervention on periodontal health and metabolic and inflammatory profiles among pregnant women with periodontitis receiving prenatal care in a Brazilian public health centre. 69 pregnant women (gestational age ≤20 weeks, T0) were randomly allocated into four groups: (1) fortified sachet (vitamin D and calcium) and powdered milk plus periodontal therapy during pregnancy (early PT) (n = 17); (2) placebo sachet and powdered milk plus early PT (n = 15); (3) fortified sachet and powdered milk plus late PT (after delivery) (n = 19); (4) placebo sachet and powdered milk plus late PT (n = 18). Third trimester (T1) and 6–8 weeks postpartum (T2) exploratory outcomes included periodontal health (% sites with bleeding on probing (BOP)), glucose, insulin, C-Reactive Protein, serum calcium and vitamin D. The mean BOP was significantly reduced in the early PT groups, while BOP worsened in the late PT groups. No significant effect of fortification on BOP was observed. Changes in glucose levels and variation on birthweight did not differ among groups This feasibility trial provides preliminary evidence for estimating the minimum clinically important differences for selected maternal outcomes. A large-scale trial to evaluate the interventions’ clinical benefits and cost-effectiveness is warranted.     

Mundgesundheitskompetenz von Menschen mit Migrationshintergrund – Erste Auswertungen der MuMi-Studie

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Erste Studien heben den Migrationshintergrund von Menschen in Deutschland als eigenständigen Risikofaktor für eine...     

Pancreatic growth after pancreatico-biliary diversion does not increase the capacity to secrete amylase

BACKGROUND/AIM: Cholecystokinin (CCK) stimulates secretion and evokes a hyperplastic response in the rat pancreas. The aims of this study were to measure the effect of chronic hyperCCKemia induced by pancreatico-biliary diversion (PBD) on pancreatic enzyme concentrations, on amylase secretion by dispersed acinar cells, and on the CCK-stimulated secretion of pancreatic juice in PBD-operated rats. MATERIAL AND METHODS: Forty-five Sprague-Dawley male rats had either PBD or sham operation 4 weeks before sacrifice or additional experiments. In the first study, 25 rats (13 PBD and 12 sham-operated rats) were either freely fed or fasted overnight before sacrifice. The pancreas was dissected out, weighed and analyzed. In the second study, the rats (6 PBD and 7 sham-operated rats) were fasted overnight before pancreatic acini were prepared. Secretion of amylase during stimulation of acini with CCK-8S and carbachol was measured. In the third study (5 sham-operated and 4 PBD rats), the rats were fasted overnight before basal and CCK-stimulated secretion was measured in vivo. RESULTS: PBD-operated rats showed a threefold increase in pancreatic wet weight with increased contents of DNA, protein and water. The concentration of pancreatic amylase was 7-12% of that found in control animals. The concentrations of trypsin and lipase were also lowered. Stimulation of dispersed pancreatic acini with CCK-8S or carbachol resulted in secretion of amylase to a similar extent in PBD and sham-operated rats. There was no difference in the secretion of pancreatic juice in response to CCK, but although the output of amylase from PBD-operated rats increased with CCK, it remained at a low level throughout the study period. CONCLUSION: PBD evoked hyperplastic changes in the rat pancreas and decreased the concentrations of amylase, trypsin and lipase. However, the capacity of acinar cells to secrete amylase remained intact. The stimulated pancreatic secretion was not changed in volume, but the output of amylase was low in PBD-operated rats. The findings are consistent with the idea that the enlargement of the pancreas following PBD does not improve the secretory capacity.     

Quality of Life in the General Norwegian Population, Measured by the Quality of Life Scale (QOLS-N)

The main aim of the present study was to derive norms or reference values from the general Norwegian population for the Norwegian version of the Quality of Life Scale (QOLS-N). In addition, associations between socio-demographic and health variables on the level of quality of life were examined. The sample consisted of 1893 subjects from a total of 4000 randomly selected Norwegian citizens representative of the entire Norwegian population, aged 19-81. The subjects received a mailed questionnaire containing the QOLS-N. Results show that the mean quality of life score was 84.1 (SD 12.5). Women reported a higher quality of life than men. People with higher levels of education reported a higher quality of life. Those who were married or cohabitating reported the highest quality of life and those who were unemployed reported a lower quality of life than those who worked. In addition, people reporting long-term diseases or health problems scored significantly lower on quality of life. These results could serve as reference values for the level of quality of life, as measured by the QOLS-N in the Norwegian population.     

Isolation,characterisation and complement fixation activity of acidic polysaccharides from Argemone mexicana used as antimalarials in Mali

ContextGlobal studies on Argemone mexicana L. (Papaveraceae) traditionally used against malaria in Mali are limited to its low-mass compounds activities, and little information on its bioactive polysaccharides is available.ObjectiveThis study determines the structure and the immunomodulatory activity of polysaccharides from aerial parts of A. mexicana.Materials and methodsAcidic polysaccharides from this plant material named HMAmA1 and HMAmA2 were isolated from water extracts. Their monosaccharide composition was determined by gas chromatography. Glycosidic linkages were determined using GC-MS. NMR was also applied. The polymers were tested for effects on the human complement system in vitro at different doses.ResultsThe monosaccharide composition showed that the two polysaccharides contained in different amounts the following monomers: arabinose, rhamnose, galactose, and galacturonic acid. Overall structural analysis showed the presence of a low ratio of 1,2-linked rhamnose compared to 1,4-linked galacturonic acid with arabinogalactans substituted on position 4 of rhamnose. NMR data showed the presence of galacturonans alternated by rhamnogalacturonans bearing arabinose and galactose units. α-Linkages were found for l-arabinose, l-rhamnose and d-galacturonic acid, while β-linkages were found for d-galactose. The two polysaccharides exhibited strong complement fixation activities, with HMAmA1 being the highest potent fraction. ICH₅₀ value of HMAmA1 was 5 µg/mL, compared to the control BPII being 15.9 µg/mL.Discussion and conclusionsPolysaccharides form A. mexicana presented a complement fixation effect. The complement system is an important part of the immune defense, and compounds acting on the cascade are of interest. Therefore, these polymers may be useful as immunodulatory agents.