Ovarian Toxicity in Female Rats after Oral Administration of Melamine or Melamine and Cyanuric Acid

Although the toxicity of melamine to the kidneys and testes is well known, few studies have investigated the effects of melamine on female reproductive organs. Therefore, this study explores the effects of oral administration melamine or melamine and cyanuric acid for 28 days on the ovaries of female rats. Rats that were exposed to the mixture exhibited reduced ovarian and uterine weights, a shorter estrous cycle, and reduced serum estrogen and progesterone levels compared to rats that were exposed to melamine and control rats. Furthermore, morphological analysis revealed pathological changes in the ovaries of rats exposed to melamine or the mixture, such as more atretic follicles and necrosis of oocytes and granulosa cells. TUNEL staining revealed that the exposed groups had a higher proportion of TUNEL-positive granulosa cells than the control group, and the mRNA expressions of SOD1, GPX1, GPX2, P450scc, 17β-HSD I, and 17β-HSD II were reduced in the exposure groups compared with the control group. These results indicated that exposure to melamine alone or to the melamine-cyanuric acid mixture could damage the ovaries in rats.     

Ketoprofen Absorption by Muscle and Tendon after Topical or Oral Administration in Patients Undergoing Anterior Cruciate Ligament Reconstruction

Topical ketoprofen patches are widely used in the treatment of musculoskeletal pain, but the pharmacokinetics of ketoprofen following topical application remain unclear. This open-label, single-dose pharmacokinetic study was designed to determine the concentrations of ketoprofen in the semitendinosus muscle/tendon and plasma after topical application or oral administration to patients scheduled for anterior cruciate ligament reconstruction. Two ketoprofen patches (20 mg each) were applied over the semitendinosus muscle/tendon for 1, 6, 14, or 20 h before surgery in 21 patients, while one sustained-release 150 mg ketoprofen capsule was administered to six patients 14 h before surgery. Ten untreated patients served as the control group. The main outcome measures were the semitendinosus muscle/tendon and plasma concentrations of ketoprofen at 1, 6, 14, and 20 h. Ketoprofen was detected in the semitendinosus muscle/tendon from about 1 h after topical application. The peak concentration was reached at 6 h, and it decreased gradually until 20 h, although the concentration at 20 h was still higher than that at 1 h. Unlike the tissue concentration, the plasma concentration of ketoprofen increased gradually after topical application. At 14 h, there was no significant difference of the tissue concentration between the topical and oral groups, although the plasma concentration was about 17-fold higher in the oral group than in the topical group. In conclusion, following topical application in a patch, ketoprofen shows rapid and sustained delivery to the underlying tissues without a significant increase of the plasma drug concentration.     

Oral Administration of Alginic Acid Oligosaccharide Suppresses IgE Production and Inhibits the Induction of Oral Tolerance

We have found that alginic acid oligosaccharide (ALGO) enhanced Th1 by promoting IL-12 production, suggesting that ALGO can be applied as an anti-allergic food. In this study we examined both positive and negative functions of ALGO. First we investigated the anti-allergic activity of ALGO, as a positive function, when orally administered. IgE production was significantly inhibited in mice fed ALGO as compared to control mice. This result indicates that ALGO had anti-allergic activity even when orally administered. On the other hand, we also found a negative function of ALGO. Oral co-administration of a protein antigen and ALGO inhibited the induction of oral tolerance to the protein. These data indicate the potential of ALGO as an anti-allergic food material and the necessity of further examination to determine a safe method application.     

Pharmacokinetics and Pharmacodynamic Effects of Flunixin after Intravenous,Intramuscular and Oral Administration to Dairy Goats

The pharmacokinetics and the prostaglandin (PG) synthesis inhibiting effect of flunixin were determined in 6 Norwegian dairy goats. The dose was 2.2 mg/kg body weight administered by intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) routes using a cross-over design. Plasma flunixin content was analysed by use of liquid chromatography and the PG synthesis was evaluated by measuring plasma 15-ketodihydro-PGF_2α by a radioimmuno-assay. Results are presented as median (range). The elimination half-lives (t_1/2·λ) were 3.6 (2.0–5.0), 3.4 (2.6–6.8) and 4.3 (3.4–6.1) h for i.v., i.m. and p.o. administration, respectively. Volume of distribution at steady state (Vd_ss) was 0.35 (0.23–0.41) L/kg and clearance (CL), 110 (60–160) mL/h/kg. The plasma concentrations after oral administration showed a double-peak phenomenon with the two peaks occurring at 0.37 (0.25–1) and 3.5 (2.5–5.0) h, respectively. Both peaks were in the same order of magnitude. Bioavailability was 79 (53–112) and 58 (35%–120)% for i.m. and p.o. administration, respectively. 15-Ketodihydro-PGF_2α plasma concentrations decreased after flunixin administration independent of the route of administration.     

Potassium Fluxes during Potassium Absorption by Intact Barley Plants of Increasing Potassium Content

The presence of previously absorbed K in plants caused a marked reduction in the short term influx of ⁸⁶Rb-labeled K into roots of barley seedlings. The influx values agreed with net K absorption rates into intact plants, thus suggesting that K efflux was negligible in comparison with influx.     

Tissue Distribution of Berberine and Its Metabolites after Oral Administration in Rats

Berberine (BBR) has been confirmed to have multiple bioactivities in clinic, such as cholesterol-lowering, anti-diabetes, cardiovascular protection and anti- inflammation. However, BBR’s plasma level is very low; it cannot explain its pharmacological effects in patients. We consider that the in vivo distribution of BBR as well as of its bioactive metabolites might provide part of the explanation for this question. In this study, liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MSⁿ-IT-TOF) as well as liquid chromatography that coupled with tandem mass spectrometry (LC-MS/MS) was used for the study of tissue distribution and pharmacokinetics of BBR in rats after oral administration (200 mg/kg). The results indicated that BBR was quickly distributed in the liver, kidneys, muscle, lungs, brain, heart, pancreas and fat in a descending order of its amount. The pharmacokinetic profile indicated that BBR’s level in most of studied tissues was higher (or much higher) than that in plasma 4 h after administration. BBR remained relatively stable in the tissues like liver, heart, brain, muscle, pancreas etc. Organ distribution of BBR’s metabolites was also investigated paralleled with that of BBR. Thalifendine (M1), berberrubine (M2) and jatrorrhizine (M4), which the metabolites with moderate bioactivity, were easily detected in organs like the liver and kidney. For instance, M1, M2 and M4 were the major metabolites in the liver, among which the percentage of M2 was up to 65.1%; the level of AUC _(0-t) (area under the concentration-time curve) for BBR or the metabolites in the liver was 10-fold or 30-fold higher than that in plasma, respectively. In summary, the organ concentration of BBR (as well as its bioactive metabolites) was higher than its concentration in the blood after oral administration. It might explain BBR’s pharmacological effects on human diseases in clinic.     

Rubidium and Potassium Absorption by Bean-leaf Slices Compared to Sodium Absorption

At salt concentrations of 0.1 mM as well as of 5.0 mM, the ²²Na⁺ absorption capacity of bean (Phaseolus vulgaris L. cv. ‘Brittle Wax’) leaf tissue increased during the period of leaf expansion and decreased rapidly after leaf maturation. The absorption capacity for ⁸⁶Rb⁺ and ⁴²K⁺ was highest in very young leaves and decreased continuously in expanding and in mature leaves. The ⁸⁶Rb⁺ absorption capacity of mature leaves was not increased by detopping the plants; this senescence-retarding treatment more than doubled ²Na⁺ absorption. The absorption of ²²Na⁺ by bean-leaf slices was not enhanced by light, whereas ⁸⁶Rb⁺ and ⁴²K⁺ absorption was much affected. Previously absorbed ⁸⁶Rb⁺ and ⁴²K⁺ were more available for exchange than ²²Na⁺.     

Interaction Between Potassium and Calcium in Their Absorption by Intact Barley Plants. II. Effects of Calcium and Potassium Concentration on Potassium Absorption

Increasing concentrations of K (20, 200, 2000 μm) in the nutrient solution depressed Ca content and concentration in barley plants growing in nutrient solutions of low Ca concentrations (250 and 2500 μm). Increasing K from 20 to 200 μm depressed Ca absorption more than increasing K from 200 to 2000 μm K.     

Turnover of Free Sialic Acid, CMP-Sialic Acid, and Bound Sialic Acid In Rat Brain

Abstract: Adult male rats were injected intraventricularly with N-[³H]acetylmannosamine. After different time intervals the rats were killed and free sialic acid, CMP-sialic acid, lipid- and protein-bound sialic acid were isolated from brain and the specific radioactivities determined. Maximal specific radioactivity was reached after approximately 4 h for CMP-sialic acid, after 10–12 h for free sialic acid and after approximately 42 h for lipid-and protein-bound sialic acid. After some days the specific radioactivities of all four pools were the same and decreased equally, with a calculated turnover rate of approximately 3.5 weeks. The conclusion was that this phenomenon was the result of reutilisation of sialic acid and/or precursors. Therefore, the calculated turnover is not the turnover of bound sialic acid, but merely the rate of leakage of sialic acid and/or precursors out of the brain, so that no real turnover can be measured by this method. The first few hours after injection the specific radioactivity of CMP-sialic acid rose above that of free sialic acid. It is supposed that a compartmentalization exists of free sialic acid. The newly synthesized sialic acid molecules are not secreted into the cytoplasmic pool but are preferentially used for the synthesis of CMP-sialic acid. The results and conclusions are discussed in view of the general problems concerning turnover measurements of glycoconjugates.     

Probiotic Administration Increases Amino Acid Absorption from Plant Protein: a Placebo-Controlled,Randomized, Double-Blind,Multicenter, Crossover Study

The fate of dietary protein in the gut is determined by microbial and host digestion and utilization. Fermentation of proteins generates bioactive molecules that have wide-ranging health effects on the host. The type of protein can affect amino acid absorption, with animal proteins generally being more efficiently absorbed compared with plant proteins. In contrast to animal proteins, most plant proteins, such as pea protein, are incomplete proteins. Pea protein is low in methionine and contains lower amounts of branched-chain amino acids (BCAAs), which play a crucial role in muscle health. We hypothesized that probiotic supplementation results in favorable changes in the gut microbiota, aiding the absorption of amino acids from plant proteins by the host. Fifteen physically active men (24.2 ± 5.0 years; 85.3 ± 12.9 kg; 178.0 ± 7.6 cm; 16.7 ± 5.8% body fat) co-ingested 20 g of pea protein with either AminoAlta™, a multi-strain probiotic (5 billion CFU L. paracasei LP-DG® (CNCM I-1572) plus 5 billion CFU L. paracasei LPC-S01 (DSM 26760), SOFAR S.p.A., Italy) or a placebo for 2 weeks in a randomized, double-blind, crossover design, separated by a 4-week washout period. Blood samples were taken at baseline and at 30-, 60-, 120-, and 180-min post-ingestion and analyzed for amino acid content. Probiotic administration significantly increased methionine, histidine, valine, leucine, isoleucine, tyrosine, total BCAA, and total EAA maximum concentrations (Cmax) and AUC without significantly changing the time to reach maximum concentrations. Probiotic supplementation can be an important nutritional strategy to improve post-prandial changes in blood amino acids and to overcome compositional shortcomings of plant proteins. ClinicalTrials.gov Identifier: ISRCTN38903788

     

Slow Absorption of Conjugated Linoleic Acid in Rat Intestines,and Similar Absorption Rates of 9c,11t-Conjugated Linoleic Acid and 10t,12c-Conjugated Linoleic Acid

We have previously shown that the 9c,11t-conjugated linoleic acid (CLA) concentration was always significantly higher than the 10t,12c-CLA concentration following the administration of these compounds to mice and rats, and considered that structural differences between the conjugated double bonds in these isomers affected absorption in the small intestine. This study investigates the absorption of CLA in the rat intestine by a lipid absorption assay of lymph from the thoracic duct. In Study 1, we used safflower oil and a triacylglycerol form of CLA (CLA-TG), while in Study 2, we used 9c,11t-CLA and 10t,12c-CLA. The cumulative recovery of CLA was lower than that of linoleic acid until two hours after sample administration. There was no difference in the extent of lymphatic recovery of 9c,11t-CLA and 10t,12c-CLA after the administration of CLA-TG, 9c,11t-CLA, and 10t,12c-CLA to the rats, suggesting that geometrical and positional isomerism of the conjugated double bonds did not influence the absorption.     

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     

Intestinal Absorption of Calcium-47 after Treatment with Oral Oestrogen-gestogens in Senile Osteoporosis

Intestinal absorption of radiocalcium was measured in 15 postmenopausal women with osteoporosis before and after six months'' treatment with an oral oestrogen-gestogen combination. Comparison with a control group indicated a significant improvement in intestinal absorption after treatment. Though there is no evidence that oestrogens have an anabolic effect on human bone, these results indicate that they affect the intestinal absorption of calcium directly.     

The Absorption of Potassium Ions by Plasmolysed Cells

The absorption of potassium ions by cells of red beetroot tissueplasmolysed in various media has been examined and comparedwith that of unplasmolysed cells under similar experimentalconditions. It is established that although the plasmolysing agents in themselvestend to promote the absorption of ions at the concentrationsemployed, the effect of plasmolysis is to inhibit the rate ofpotassium uptake. Evidence is provided that this is due to anincrease in the rate of leakage of ions from plasmolysed cells,and to a reduction of gross uptake. These results are discussed in terms of the structural and physiologicalchanges which are associated with plasmolysis. It is concludedthat alterations in the surface area, and thickness or densityof the protoplasts, modifications of the vacuolar concentrationof ions, and respiratory influences are all involved. Anotherfactor, the nature of which has not been elucidated, also appearsto be involved.