Interaction of coenzyme Q10 with the intestinal drug transporter P-glycoprotein

In clinical trials, patients usually take many kinds of drugs at the same time. Thus, drug-drug interactions can often directly affect the therapeutic safety and efficacy of many drugs. Oral delivery is the most desirable means of drug administration. Changes in the activity of drug transporters may substantially influence the absorption of administered drugs from the intestine. However, there have been a few studies on food-drug interactions involving transporters. It is important to be aware of the potential of food-drug interactions and to act in order to prevent undesirable and harmful clinical consequences. Coenzyme Q10 (CoQ10) is very widely consumed by humans as a food supplement because of its recognition by the public as an important nutrient in supporting human health. Since intestinal efflux transporter P-glycoprotein (P-gp) is one of the major factors in drug-drug interactions, we focused on this transporter. We report here for the first time that CoQ10, which is widely used as a food supplement, affects the transport activity of P-gp.     

Humus composition and humification degree of humic acids of alpine meadow soils in the northeastern part of the Qinghai–Tibet Plateau

The characteristics of humus composition are important for understanding the mechanism of carbon storage in the Qinghai–Tibet Plateau. The aim of this study was to characterize the quality of soil organic matter (SOM) in this region. Soil samples from four soil profiles in fenced study sites in the alpine grassland were collected at altitudes of 4200, 4000, 3800, and 3400 m, along the southwest facing slope in the Qilian Mountains. The humus composition and humification degree of the humic acid (HA) were determined by two methods: (1) extraction with 0.5% sodium hydroxide (NaOH) followed by 0.1 M sodium pyrophosphate (Na₄P₂O₇) (OH-PP method); and (2) treating once with 0.1 M hydrochloric acid (HCl) followed by extracting with 0.5% NaOH (Cl-OH method). Physico-chemical analysis revealed higher exchangeable cation content and higher base saturation ratios could be related to slightly acidic to neutral soils, which could be regarded as calcium (Ca)-rich soils. The amounts of combined-form HAs obtained by HCl pretreatment (HA_Cl – HA_OH; ?HA_Cl) were remarkably higher than those extracted with Na₄P₂O₇ (HA_PP), indicating that the combined form of HAs is mainly Ca. In addition, the proportion of HA_PP in the total HAs extracted with both NaOH and Na₄P₂O₇ (HA_OH + HA_PP) obtained in the OH-PP method increased with soil depth and decreasing elevation, indicating that HAs associated with aluminum (Al) and iron (Fe) were distinguished in the subsoils of lower elevation. Therefore, the formation of the organo-mineral complex may contribute to stabilizing SOM in the Qinghai–Tibet Plateau. Moreover, Type A-HA with the highest degree of humification was obtained from the deeper horizons with the Cl-OH method and almost all horizons by extraction with Na₄P₂O₇ in the OH-PP method. Further studies using various spectroscopic analyses are necessary to elucidate the chemical properties of SOM in this region.     

Relationship of Cell Proliferating Marker Expressions with PGE(2) Receptors in Regenerating Rat Renal Tubules after Cisplatin Injection

Cisplatin, an anticancer drug, is well known to have nephrotoxicity as an adverse effect. We investigated the expressions of cell cycle markers and prostaglandin E(2) (PGE(2)) receptors (EP) in the affected renal tubules in rats injected with a single dose (6 mg/kg body weight) of cisplatin. On days 1-3 after dosing, the affected renal epithelial cells were almost desquamated, showing necrosis. On day 5 onwards, the renal tubules were rimmed by flattened or cuboidal epithelial cells with basophilic cytoplasm; BrdU-immunopositive cells began to significantly increase, indicating regeneration. Simultaneously, TUNEL-positive apoptotic cells were also seen. On days 1-5, cyclin D1-immunopositive cells were decreased with an increased expression in p21 mRNA, indicating G(1) arrest in the cell cycle. The affected renal epithelial cells began to react to EP4 receptor, but not to EP2 receptor. Some EP4 receptor-reacting epithelial cells gave a positive reaction to BrdU or cyclin D1. Collectively, the affected renal tubules underwent various alterations such as necrosis, apoptosis, regeneration and G(1) arrest; the aspects might be influenced by endogenous PGE(2) through EP4 receptor.     

Usninsäure aus jugoslawischen Flechten und ihre antibiotische Wirksamkeit

Zusammenfassung Es wurde L-Usninsäure aus jugoslawischen Flechten in reiner Form isoliert. Der Schmelzpunkt der Substanz (zwei Proben) ist bei . Die Elementarmikroanalyse sowie die qualitativen Reaktionen entsprechen auch der reinen L-Usninsäure. Ein drittes isoliertes Präparat hatte den Schmp. bei 196° und . Das Präparat mit dem Schmp. 204° wurde auf seine bakteriostatische Wirksamkeit verwendet, und zwar in fein pulverisierter Form in einer Blut-Agar-Nährlösung suspendiert (Rinnenmethode), sowie mit der Routinemethode der Diskuse. Ein Lösungsvermittler für die sehr schwer in Wasser lösliche Usninsäure wurde nicht angewendet.Die Methode der Suspendierung in dem Nährmedium ist etwas empfindlicher, aber weniger praktisch. L-Usninsäure wirkt in vitro bakteriostatisch auf Mikroorganismen der Kugelform und zeigt so eine Ähnlichkeit mit Penicillin. Sie entwickelt eine Wirksamkeit gegenüber Streptokokken, Staphylokokken und Pneumokokken. Auf grampositive Bacillen zeigt sie in Suspensions-Konzentrationen von 0,25, 0,5 und 1,0% keine Wirksamkeit, was mit der sehr schweren Löslichkeit der Substanz in Wasser im Zusammenhang stehen wird.Die Wirkungsweise der Usninsäure steht am nächsten dem Penicillin, obwohl dieselbe schwächer ist als beim letzteren.Gegen Penicillin resistente Stämme zeigten sich als empfindlich auf Usninsäure.Die Versuche werden fortgesetzt.

---

Summary L-usninic acid was isolated in pure form from lichens of Jugoslavia. The melting point of the substance (two samples) lies at . The elementary microanalysis and the qualitative reactions are in accordance with the pure L-usninic acid. A third isolated preparation showed the melting point 196° C, and . The preparation (melting point 204°) was tested on the bacteriostatic effet, specifically pulverized suspended in a blood-agar-culture solution (Rinnen-method) (channel-method), as well as with the routine method of the discuse. A medium to rise the solubility in water of the very little soluble usninic acid was not used.The method of suspending this acid in the culture solution is somewhat more sensitive, but less usefull. L-usninic acid has in vitro a bacteriostatic effect on spherical microorganisms in resemblance with penicilline. It is effective against streptococci, staphylococci and pneumococci. On Gram-positive bacillae the usninic acid has no effect in concentrations of 0,25 0,5 and 1,0 % of the suspensions, probably in consequence of its very small solubility.The effectiveness of the usninic acid is analogous to that of the penicilline, but weaker than the last-named. Stocks resistant against penicilline showed sensible against usninic acid.The researches will be continued.

     

A primary hepatic plasma cell tumor in a dog

An 8-year-old female Shetland sheep dog had hyperproteinemia with a monoclonal gammopathy and a solid mass on the liver, which was histologically diagnosed as a plasma cell tumor. After the treatment of surgery and chemotherapy, serum protein level reduced to the normal range and the gammopathy was disappeared. These findings indicate the plasma cell tumor developed primarily from the liver.     

Aggregability and post-transfusion survival of canine platelets in stored whole blood

The effects of whole blood storage time on platelet aggregation and on post-transfusion platelet survival time were assessed in dogs. Citrate phosphate dextrose adenine-1 (CPDA-1) was used as a blood cell preservative. Storage time dependent decay of platelet aggregability was assessed. Platelet aggregation responses to collagen and ADP were maintained for at least 8 hr at room temperature. During blood storage, immunoglobulin became nonspecifically bound to platelets, suggesting the potential for immune destruction of platelets by the mononuclear phagocyte system after transfusion. To assess this assumption, the survival times of infused platelets, which were stored for 0 to 8 hr in whole blood, were measured. Post-transfusion survival of platelets was not affected by these storage times. These results suggest that canine platelets maintain viability when stored at room temperature for up to 8 hr in CPDA-1 treated whole blood intended for transfusion.