Effects of bead size and polymerization in PMMA bone cement on vancomycin release.

Polymethylmethacrylate (PMMA) bone cement loaded with antimicrobial agents is used for the treatment and prevention of infections in orthopaedic surgery. The use of antimicrobial-loaded bone cement allows for high local doses while avoiding systemic toxicity. The release of vancomycin (VCM) from bone cement has been reported. However, the exact mechanism behind the release is unknown. We studied the influence of bead size and polymerization time on elution, and considered the release mechanism for VCM. We used CMW Endurance Bone Cement. Cements were prepared by mixing 6 g of VCM with 40 g of polymer, and then 10 g of liquid monomer was added. We kneaded and shaped the preparation into spheres containing 10.7 w/w% VCM. We measured the release of VCM from PMMA beads of three different sizes. Average weights of the beads were 0.96 g (SB) (n = 6), 2.86 g (MB) (n = 2) and 5.65 g (LB) (n = 1). Additionally, we studied beads made with different polymerization times. The polymerization time was taken as the period from the making of the beads until the start of the study, and was 15 min (B15), 20 min (B20), 60 min (B60) or 180 min (B180). The release of VCM showed a bimodal curve with a high initial release followed by a sustained release. Regarding the size of the beads, SB released 7.2%, MB released 4.3% and LB released 3.1%. Regarding polymerization time, B15 released 10.0%, B20 released 6.5%, B60 released 6.3% and B180 released 4.3%, respectively. The release of VCM from PMMA beads was influenced by bead size and polymerization time. Those beads which were smaller and had a shorter polymerization time released more VCM. Total pore volume of beads that polymerization time was 30 min after drug-release test was 1.33 times grater than that of control beads that polymerization time was one week before drug-release test. This suggested that the short polymerization time caused the beads to leak more VCM. We proposed a model with four kinds of the dissolution from bone cement. (A) Dissolution from drug particles on the cement surface. This type shows the burst effect of release curve. (B) Dissolution from micropores near the cement surface. It is responsible the grater part of the curve based on Higuchi's equation. (C) Dissolution from ink-bottle-neck-type micropores. It causes a release based on a non-Higuchi's equation. (D) No dissolution from Encapsulation micropores.It can be concluded that the release of VCM from bone cements is controlled by a combination of surface area and polymerization time. PMMA beads loaded with VCM should be used carefully in orthopaedic surgery, taking into consideration the influence of bead size and polymerization time.

Effects of Hoelen on the efferent activity of the gastric vagus nerve in the rat.

Hoelen is used to treat gastric disease in Eastern traditional medicine. The efferent activity on the gastric vagus nerve was studied in the rat, and the activity was found to increase after administration of Hoelen into the duodenum. In addition, we examined the effect of Hoelen fractions. Both the fraction containing polysaccharide and the triterpenoid-rich fraction increased activity significantly. Hoelen would thus appear useful for treating gastric disease by activating efferent activity of the gastric vagus nerve through the action of triterpenoid and polysaccharide.

Studies on anti-allergic components in the roots of Asiasarum sieboldi.

The methanolic extract of the roots of Asiasarum sieboldi has been evaluated for anti-allergic effects on various experimental models in vitro and in vivo. Bioassay-guided fractionation of the methanolic extract resulted in isolation of suppressive compounds in the PCA test: methyleugenol (1), elemicin (2), gamma-asarone (3), (-)-asarinin (4), and (-)-sesamin (5). Furthermore, elemicin (2) and (2E,4E,8Z,10E)-N-isobutyl-2,4,8,10-dodecatetraenami de (6) were found to exhibit an inhibitory action on 5-lipoxygenase (5-LOX) from RBL-1 cells. 3',4'-Dimethoxycinnamaldehyde (7) and xanthoxylol (8) potently reduced the contractile response of guinea pig ileal strips to LTD4.

Effect of Pinellia ternata tuber on the efferent activity of the gastric vagus nerve in the rat.

Effect of intraduodenal infusion with the hot aqueous extract of Pinellia ternata tuber on the efferent discharges in the gastric branch of the vagus nerve was observed in the anesthetized rat. The infusion of the extract in doses of 2-15O mg per animal (c.a. 300 g, b.wt.) resulted in a dose-related increase in efferent activity of the vagal gastric nerve. The enhancement of the nerve activity following administration of 150 mg of this substance lasted longer than 90 min. It was observed that the suppressive effect on vagal gastric activity due to apomorphine and copper sulfate was antagonized by prior administration of the extract. From these observations it is suggested that Pinellia tuber acts as a facilitatory agent on gastric function.

Synthesis and protective effect of 1,3,5-triazine derivatives, leukotriene C4 antagonist, on HCl.ethanol-induced gastric lesions in rats.

2,4-Diamino-[E]-6-[2-(3-pyridyl)ethenyl]-1,3,5-triazine (3a), leukotriene C4 (LTC4) antagonist, was found to possess a protective effect on HCl.ethanol-induced gastric lesions. Analogues of 3a were synthesized and evaluated for the effect as well as antagonistic activity against LTC4-induced contraction. Seven compounds (3a-d, f-h) exhibited a potent protective effect on gastric lesions which was considered to be based on the antagonistic activity against LTC4. The structure-activity relationships of the derivatives (3a-k) are discussed.

Calcium/calmodulin-mediated action of calcitonin on lipid metabolism in rats.

The effects of calcitonin on lipid metabolism were investigated in three kinds of rats, one strain of rabbits, and a primary culture of rat hepatocytes. In a short-term experiment, calcitonin decreased serum cholesterol and triglycerides after injection in rats on either an ordinary or high-fat diet. In a long-term experiment, calcitonin decreased the serum cholesterol and triglycerides in uremic rats, hypothalamic obese rats, and Watanabe-heritable hyperlipidemic rabbits. In cultured hepatocytes, calcitonin reduced the incorporation of [14C]acetate into cholesterol and triglycerides in a dose-dependent way. Treatment with W7, a calmodulin inhibitor, overcame the decrease caused by calcitonin in serum lipids in rats and in the synthesis of triglycerides from acetate or palmitate in the hepatocytes, but did not alter the intracellular cAMP level or incorporation of [32P]Pi into PI in the cells. The results suggest that calcitonin lowers serum lipid levels and lipogenesis in hepatocytes in a calcium/calmodulin-dependent way.

Deranged metabolism of lipids in patients with chronic renal failure: possible role of secondary hyperparathyroidism.

We wished to investigate the pathophysiology of hypertriglyceridemia in chronic renal failure. Our subjects were 30 patients under hemodialysis for at least five years who had never taken vitamin D analogues or calcitonin preparations. During those five years, triglycerides were high, with no significant changes, although the cholesterol level decreased significantly 10 to 12 months after the first hemodialysis treatment. There was a significant correlation between alkaline phosphatase and triglycerides (p less than 0.025) in these patients in the same assay. In the two patients with hypertriglyceridemia, serum triglycerides decreased to within the normal range by six months after parathyroidectomy, and remained there 30 months after surgery. These results suggested that secondary hyperparathyroidism may be involved in the pathophysiological mechanism of hypertriglyceridemia seen in chronic renal failure.

Nutrition and renal osteodystrophy.

Nutritional factors, especially calcium, calorie and fat intakes may be important in the treatment with active vitamin D, so that the effect appears more efficient. Incidence of bone changes, due to hyperparathyroidism in diabetic nephropathy, was less than that in non-diabetic patients under hemodialysis. No effect of control status of diabetes mellitus was demonstrated, regarding incidence of subperiosteal resorption of finger bones. Bone mass was decreased in diabetic patients in whom the control of blood glucose was inadequate.