New simulation model for bone formation markers in osteoporosis patients treated with once-weekly teriparatide

Daily 20-mg and once-weekly 56.5-mg teriparatide（parathyroid hormone 1–34） treatment regimens increase bone mineral density（BMD） and prevent fractures, but changes in bone turnover markers differ between the two regimens. The aim of the present study was to explain changes in bone turnover markers using once-weekly teriparatide with a simulation model. Temporary increases in bone formation markers and subsequent decreases were observed during once-weekly teriparatide treatment for 72 weeks. These observations support the hypothesis that repeated weekly teriparatide administration stimulates bone remodeling, replacing old bone with new bone and leading to a reduction in the active remodeling surface. A simulation model was developed based on the iterative remodeling cycle that occurs on residual old bone. An increase in bone formation and a subsequent decrease were observed in the preliminary simulation. For each fitted time point, the predicted value was compared to the absolute values of the bone formation and resorption markers and lumbar BMD. The simulation model strongly matched actual changes in bone turnover markers and BMD. This simulation model indicates increased bone formation marker levels in the early stage and a subsequent decrease. It is therefore concluded that remodeling-based bone formation persisted during the entire treatment period with once-weekly teriparatide.

Encapsulated islets transplantation: Past, present and future

Islet transplantation could become an ideal treatment for severe diabetes to prevent hypoglycemia shock and irreversible diabetic complications, once some of the major and unresolved obstacles are overcome, including limited donor supplies and side effects caused by permanent immunosuppressant use. Approximately 30 years ago, some groups succeeded in improving the blood glucose of diabetic animals by transplanting encapsulated islets with semi-permeable membranes consisting of polymer. A semi-permeable membrane protects both the inner islets from mechanical stress and the recipient’s immune system (both cellular and humoral immunities), while allowing bidirectional diffusion of nutrients, oxygen, glucose, hormones and wastes, i.e., immune-isolation. This device, which enables immune-isolation, is called encapsulated islets or bio-artificial pancreas. Encapsulation with a semipermeable membrane can provide some advantages: (1) this device protects transplanted cells from the recipient’s immunity even if the xenogeneic islets (from large animals such as pig) or insulin-producing cells are derived from cells that have the potential for differentiation (some kinds of stem cells). In other words, the encapsulation technique can resolve the problem of limited donor supplies; and (2) encapsulation can reduce or prevent chronic administration of immunosuppressants and, therefore, important side effects otherwise induced by immunosuppressants. And now, many novel encapsulated islet systems have been developed and are being prepared for testing in a clinical setting.

Intravenous administration of adipose-derived stromal cells does not ameliorate bleomycin-induced lung injury in rats

Background: Mesenchymal stromal cells (MSCs) have been studied intensively in regenerative medicine. Among MSCs, adipose tissue-derived stromal cells (ASCs) are relatively easy to obtain from a patient. Since ASCs are ideal candidates for use in the treatment of disease states including pulmonary fibrosis, we investigated whether intravenous injection of ASCs could exert a therapeutic effect against bleomycin-induced lung injury in rats. Methods: Rats were intratracheally administered bleomycin, and one week later ASCs were isolated and cultured. Two weeks after bleomycin treatment ASCs or PBS (phosphate-buffered saline) were injected to the rats. Three or six weeks after bleomycin instillation, the total cell counts and their profile in bronchoalveolar lavage fluid (BALF) were measured, and a histological evaluation was semi-quantitatively assessed for the injured lungs, followed by cell tracing. Results: The BALF cell counts and its profiles were not significantly different in the ASCs and PBS groups. Furthermore, ASC treatment led to no significant histological effect compared with the PBS treatment. Using a fluorescent cell tracer, it was noted that the ASCs homed to the injured lung areas, but some ASCs accumulated around scars, and scarcely migrated into the fibrotic areas. Conclusions: In the present study, the intravenous administration of ASCs could not reduce the severity of bleomycin-induced lung injury in a rat model. Although the ASC counts and passage numbers were suitable, the older age and fibrotic disease stage of the rats were likely responsible for the treatment failure.

Observation of the esophagus, pharynx and lingual root by gastrointestinal endoscopy with a percutaneous retrograde approach

AIM:To evaluate the efficacy of retrograde observation of the esophagus, pharynx, larynx and lingual root. METHODS:With the beagle dog under anesthesia, the anterior wall of the stomach was fixed on the abdominal wall in a similar way to percutaneous endoscopic gastrostomy. The gastrointestinal scope was inserted via a 12 mm laparoscopic port for subsequent retrograde observation from stomach to the oral cavity. RESULTS:With this technique, direct observation of gastric cardia was possible without restriction. The cervical esophagus was dilated well, also allowing clear observation of the hypopharyngo-esophageal junction. If the tongue was manually pulled out forward, observation of the lingual root was possible.CONCLUSION: This procedure is easy and effective for pre-treatment evaluation of the feasibility of endoscopic resection in cases of superficial carcinoma of head and neck.

Implementation of soft microfingers for a hMSC aggregate manipulation system

This paper describes a pneumatic balloon actuator(PBA)composed of polydimethylsiloxane(PDMS)for cellular aggregate manipulation.We evaluated the ability of the microdevice to manipulate a tiny and sensitive cellular aggregate without causing serious damage.We used human mesenchymal stem cells(hMSCs)for the cellular aggregate.We describe the design,fabrication,characterization and operation of the soft microfingers to pinch and release a spherical hMSC aggregate(φ200μm),and we employed a PBA to serve as an artificial muscle to drive the microfingers.A design of the microfingers in terms of dimensions,generated force and contact conditions was accomplished.The designed dimensions of a single finger were 560μm×900μm.In summary,we demonstrate the utility of the surface modification of a fingertip for pinching and releasing a cellular aggregate and describe a manipulation system that was constructed to drive and control the microfingers.The implemented manipulation system,which is composed of microfingers and a positioning mechanism,was tested and verified in a series of operations.