A theranostic agent to enhance osteogenic and magnetic resonance imaging properties of calcium phosphate cements

With biomimetic biomaterials, like calcium phosphate cements (CPCs), non-invasive assessment of tissue regeneration is challenging. This study describes a theranostic agent (TA) to simultaneously enhance both imaging and osteogenic properties of such a bone substitute material. For this purpose, mesoporous silica beads were produced containing an iron oxide core to enhance bone magnetic resonance (MR) contrast. The same beads were functionalized with silane linkers to immobilize the osteoinductive protein BMP-2, and finally received a calcium phosphate coating, before being embedded in the CPC. Both in vitro and in vivo tests were performed. In vitro testing showed that the TA beads did not interfere with essential material properties like cement setting. Furthermore, bioactive BMP-2 could be efficiently released from the carrier-beads. In vivo testing in a femoral condyle defect rat model showed long-term MR contrast enhancement, as well as improved osteogenic capacity. Moreover, the TA was released during CPC degradation and was not incorporated into the newly formed bone. In conclusion, the described TA was shown to be suitable for longitudinal material degradation and bone healing studies.     

Late onset asthma?

A 77 yr old male was referred for dyspnoea and recurrent infections of the lower airways for the previous five months. On the lateral chest roentgenogram a process in the tracheal area was found, and during bronchoscopy a polypoid tumour was seen about four centimetres above the main carina. It appeared to be a benign endotracheal tumour which was removed after coagulation by a Neodymium yttrium aluminium garnet (YAG) laser.     

Smoking and airway hyperresponsiveness especially in the presence of blood eosinophilia increase the risk to develop respiratory symptoms: a 25-year follow-up study in the general adult population.

Airway hyperresponsiveness (AHR) constitutes a risk for development of respiratory symptoms. We assessed whether blood eosinophilia (>/= 275 eosinophils/microliters), skin test positivity (sum score >/= 3) and cigarette smoking (never, ex-smoker, 1-14 cig/d, 15-24 cig/d, >/= 25 cig/d) at the first of two successive surveys are related to the development of respiratory symptoms (chronic cough or phlegm, bronchitis, persistent wheeze, dyspnea, and asthma) at the second survey, and whether these relations are the same in subjects with (PC10 相似文献   

Inhibition of glycosaminoglycan synthesis in anatomically intact rat patellar cartilage by paracetamol-induced serum sulfate depletion

We have studied the effect of low sulfate concentrations on the glycosaminoglycan synthesis in rat patellar cartilage in vivo as well as in vitro. The oral administration of 200 mg/kg paracetamol to male Wistar rats resulted in a significant reduction of the serum sulfate concentration. Reduced serum sulfate availability resulted in a 34% decrease of glycosaminoglycan synthesis in patellar cartilage. This is due to sulfate depletion since paracetamol had no direct effects on glycosaminoglycan synthesis and a slight but significant inhibitory effect on the catabolism of radiolabeled glycosaminoglycans in vitro. The glycosaminoglycans synthesized at low sulfate concentrations in vivo were similar to the glycosaminoglycans synthesized at physiological sulfate concentrations. Studying the effect of sulfate availability in vitro on glycosaminoglycan synthesis in patellar cartilage we found that incubation of rat patellae in medium containing less than 0.5 mM inorganic sulfate led to a decreased sulfate incorporation. The use of potential sulfate decreasing drugs can lead to inhibition of glycosaminoglycan synthesis. This argues for a reconsideration of the use of these drugs in patients with already dysfunctioning cartilage metabolism as in rheumatoid arthritis and osteoarthrosis.     

Interconnections of the upper ventral rami of the human sacral plexus: A reappraisal for dorsal rhizotomy in neurostimulation operations

The extension of a dorsal rhizotomy in bladder stimulation patients is partly determined by connections between the ventral rami of the second, third, and fourth sacral spinal nerves. The literature is inconclusive on interconnections of these ventral rami in the human sacral plexus. The sacral plexuses of ten human cadavers were dissected in this gross anatomy study. In nine cases a branch connecting the ventral rami of the second and third sacral spinal nerves was found. Electron microscopy demonstrated the presence of thick myelinated fibers in this branch. In the male plexuses this branch formed the only link between the second sacral spinal segment and the pelvic plexus. The ventral ramus of the second sacral nerve always contributed to the pudendal nerve, whereas involvement of the ventral rami of the first and third sacral nerves differed individually and intersexually.     

Homozygous deletion of exon 18 leads to degradation of the lysosomal α-glucosidase precursor and to the infantile form of glycogen storage disease type II

We describe two unrelated Dutch patients with typical symptoms of infantile glycogen storage disease type II (GSD II) and virtual absence of acid α-glucosidase activity in leukocytes and cultured skin fibroblasts. The patients were identified as homozygotes for a deletion of exon 18 of the acid α-glucosidase gene (GAA). The in-frame deletion manifests at the protein level in a characteristic way: the enzyme precursor is smaller than normal and degraded in the endoplasmic reticulum or Golgi complex. These cases present an evident example of a genotype-phenotype correlation in glycogen storage disease type II.     

Creation of four consecutive instantaneous steady-state plasma concentration plateaus of theophylline and enprofylline by repeated infusions with exponentially decreasing delivery rates

Summary Repeated exponentially decreasing influsions have been used to administer theophylline and enprofylline to show whether it would be feasible to create consecutive plasma concentration plateaus within a few hours. The infusions were carried out on two separate days in 8 stable asthmatics. Before the infusion experiments, the pharmacokinetics of the substances in the individual subjects were determined on a separate day.Plasma concentration rose to the desired level within 5 min after the start of the infusion at each dose level and a stable plasma concentration plateau was maintained during the following 90 min of the infusion. It was possible to achieve 4 subsequent concentration plateaus within a 6 h period. Use of this infusion method resulted in predictable plasma concentrations at all levels and so the method appears safe when the required plasma concentrations are below the toxic level. Apart from clinical situations where effective dosages of drugs must be administered rapidly, the method showed be useful in pharmacological dose-response studies.     

Pulmonary gas transfer 20 years after pneumonectomy for pulmonary tuberculosis.

The changes in pulmonary function after pneumonectomy in 13 patients with pulmonary tuberculosis have been studied. The data at the time of two follow-up studies are compared with those obtained before the pneumonectomy. The first follow-up was carried out between 5 and 30 months postoperatively and the second between 20 and 24 years later. The results of this second follow-up show a relatively normal arterial oxygen saturation and gas transfer factor but an increased residual volume which cannot be explained by increasing age alone.     

Aurothiomalate inhibits COX-2 expression in chondrocytes and in human cartilage possibly through its effects on COX-2 mRNA stability

Cyclooxygenase-2 (COX-2) is expressed in rheumatoid and osteoarthritic cartilage and produces pro-inflammatory prostanoids in the joint. In the present study, we investigated the effects of disease modifying anti-rheumatic drugs on COX-2 expression in chondrocytes. Unlike the other tested drugs, aurothiomalate was found to inhibit COX-2 expression in chondrocytes. In the further studies, effects and mechanisms of action of aurothiomalate were investigated in more detail. Aurothiomalate inhibited IL-1beta-induced COX-2 protein expression and PGE(2) production in chondrocytes in a dose-dependent manner. Because aurothiomalate did not alter IL-1beta-induced mRNA levels when measured 0-3 h after addition of IL-1beta, its effects on COX-2 mRNA degradation were tested by Actinomycin D assay. The half-life of COX-2 mRNA was reduced from 3 h to less than 1.5 h in aurothiomalate-treated cells. The 3'-untranslated region (3'-UTR) of COX-2 mRNA contains an ARE element which has been shown to bind mRNA stabilizing factor HuR. Interestingly, aurothiomalate inhibited HuR expression which may explain its destabilizing effect on COX-2 mRNA. Aurothiomalate reduced COX-2 expression and PGE(2) production also in human cartilage at drug concentrations which have been measured in serum and synovial fluid during treatment with aurothiomalate. The results show that aurothiomalate reduces COX-2 expression and PGE(2) production in chondrocyte cultures and in human cartilage. The action is likely mediated by enhanced COX-2 mRNA degradation possibly through a mechanism related to reduced expression of HuR. The results provide a novel mechanism of action for aurothiomalate which may be important in the treatment of arthritis.