Climbing exercise increases bone mass and trabecular bone turnover through transient regulation of marrow osteogenic and osteoclastogenic potentials in mice.

To investigate the relationship between the effects of bone turnover and bone marrow cell development in bone cells, we developed a mouse voluntary climbing exercise model. Climbing exercise increased bone volume and transient osteogenic potential of bone marrow. This model would be suitable for investigating the mechanistic roles of mechanical loading. INTRODUCTION: The relationship between bone mass gain and local bone formation and resorption in mechanically loaded bone is not well understood. MATERIALS AND METHODS: Sixty-five C57BL/6J mice, 8 weeks of age, were assigned to five groups: a baseline control and two groups each of ground control and climbing exercise mice for 2 and 4 weeks. Mice were housed in a 100-cm tower and had to climb toward a bottle placed at the top to drink water. RESULTS: Compared with the ground control, bone mineral density of the left femur increased in the climbing mice at 4 weeks. At 2 and 4 weeks, bone formation rate (BFR/BS) of periosteal surface, the cross-sectional area, and moment of inertia were increased in the climbing mice, whereas BFR/BS and eroded surface (ES/BS) of endosteal surface did not differ. The trabecular bone volume (BV/TV) of the proximal tibia increased in climbing mice, and osteoclast surface (Oc.S/BS) and osteoclast number decreased at 2 weeks. At 4 weeks, there were increases in BV/TV and parameters of bone formation, including mineralized surface, mineral apposition rate, and bone formation rate. In marrow cell cultures from the tibia, the number of alkaline phosphatase+ colony forming units-fibroblastic and the area of mineralized nodule formation in climbing mice were increased, and the number of osteoclast-like TRACP+ multinucleated cells was lower at 2 weeks. At 4 weeks, these parameters recovered to the levels of the ground controls. CONCLUSION: Our results indicate that climbing increased trabecular bone volume and reduced bone resorption, with a subsequent increase in bone formation. Intermittent climbing downregulates marrow osteoclastogenic cells and upregulates osteogenic cells initially, but further exercise seemed to desensitize them. Cortical envelopes were enlarged earlier, but the response seems to differ from trabecular bone.     

Human urotensin-II potentiates the mitogenic effect of mildly oxidized low-density lipoprotein on vascular smooth muscle cells: comparison with other vasoactive agents and hydrogen peroxide.

Human urotensin-II (U-II) is the most potent vasoactive peptide identified to date, and may be involved in hypertension and atherosclerosis. We investigated the effects of the interactions between U-II or other vasoactive agents and mildly oxidized low-density lipoprotein (mox-LDL) or hydrogen peroxide (H2O2) on the induction of vascular smooth muscle cell (VSMC) proliferation. Growth-arrested rabbit VSMCs were incubated with vasoactive agents (U-II, endothelin-1, angiotensin-II, serotonin, or thromboxane-A2) in the presence or absence of mox-LDL or H2O2. [3H]Thymidine incorporation into DNA was measured as an index of VSMC proliferation. On interaction with mox-LDL or H2O2, U-II induced the greatest increase in [3H]thymidine incorporation among these vasoactive agents. A low concentration of U-II (10 nmol/l) enhanced the potential mitogenic effect of low concentrations of mox-LDL (120 to 337%) and H2O2 (177 to 226%). U-II at 50 nmol/l showed the maximal mitogenic effect (161%), which was abolished by G protein inactivator (GDP-beta-S), c-Src tyrosine kinase inhibitor (radicicol), protein kinase C (PKC) inhibitor (Ro31-8220), extracellular signal-regulated kinase (ERK) kinase inhibitor (PD98059), or Rho kinase inhibitor (Y27632). Mox-LDL at 5 microg/ml showed the maximal mitogenic effect (211%), which was inhibited by free radical scavenger (catalase), intracellular and extracellular antioxidants (N-acetylcysteine and probucol), nicotinamide adenine dinucleotide phosphate oxidase inhibitor (diphenylene iodonium), or c-Jun N-terminal kinase (JNK) inhibitor (SP600125). These results suggested that U-II acts in synergy with mox-LDL in inducing VSMC DNA synthesis at the highest rate among these vasoactive agents. Activation of the G protein/c-Src/PKC/ERK and Rho kinase pathways by U-II together with the redox-sensitive JNK pathway by mox-LDL may explain the synergistic interaction between these agents.     

Cleft lip-nose repair technique: Sequential repair

The results of repairing cleft lip by aesthetic plastic surgery are now excellent. However, the cleft lipnose deformity is still very difficult to repair with the present techniques. A technique that can repair the cleft lip-nose deformity with good results is presented. The technique is divided into three parts: Part I consists of nasal repair of the primary cleft lip. Part II is nasal reconstruction as a secondary operation with or without lip repair. For example, nasal reconstruction may be secondary to repair of deformities of the sill, rim, limen nasi, septum, or nasal bones. Part III is an aesthetic nasal operation such as rhinoplasty, mentoplasty, or zygomaplasty.     

Antiproliferative effects of NKH477, a forskolin derivative, on cytokine profile in rat lung allografts.

OBJECTIVE: NKH477 was recently identified as a water-soluble forskolin derivative and was reported to prolong survival of murine cardiac allografts. However, the mechanism of the efficacy is not clear in vivo. The aim of this study was to investigate the immunosuppressive effects of NKH477 on acute lung allograft rejection in the rat model and its mechanism of action in vivo. METHODS: Left lungs were transplanted orthotopically from Brown-Norway donors to Lewis recipients. Recipient rats were untreated or treated daily with different doses of NKH477. Grafts were excised on Day 3 or Day 5 to determine histopathological rejection and expressions of interleukin (IL)-2, IL-4, IL-10, and interferon (IFN)-gamma by enzyme-linked immunosorbent assay. The cytokine expression at Day 3 or Day 5 was also evaluated in recipient spleens by immunohistochemistry. Furthermore, mesenteric lymph node cells from recipients at Day 5 were cultured alone or stimulated with donor antigens for 72 hours to determine cell proliferation by means of thymidine incorporation. RESULTS: NKH477 significantly extended allograft survival time in a dose-dependent manner and reduced histopathological rejection. Treatment with NKH477 inhibited IFN-gamma and IL-10 expression, whereas expression of these cytokines were markedly upregulated in the untreated allografts. Expression of IL-2 and IL-10 also increased in the spleen of untreated allorecipients. NKH477 suppressed expression of both cytokines in the spleen. In addition, lymphocyte proliferation was inhibited in NKH477-treated recipients as compared with untreated recipients. CONCLUSION: These results suggest that NKH477 exerts an antiproliferative effect on lymphocytes in vivo with an altered cytokine profile in rat recipients of lung allografts.     

Dental management of a patient with takotsubo cardiomyopathy: a case report.

Takotsubo cardiomyopathy (TCM) is a relatively new concept in cardiovascular disease. The clinical symptoms of TCM are similar to those of a myocardial infarction, but both the mechanism and the management of TCM are different from those of myocardial infarction. The cause of TCM is unclear, but it is suggested to occur in conjunction with excessive circulating catecholamines due to stress. Thus, control of the stress reaction and restriction of catecholamine levels are considered important for prevent of TCM onset. We report the dental management of a patient with intellectual disability who had anamnesis of TCM and cardiopulmonary arrest under restraint during a previous dental appointment in another dental clinic. We used intravenous sedation with both midazolam and propofol, by which the excessive hormonal reaction that caused TCM onset and cardiopulmonary arrest was controlled, for dental treatment in our facility. All planned dental treatment was then performed without any problems.     

The effect of ganglioside on diabetic neurogenic bladder

The effect of ganglioside was studied in 6 diabetic patients with neurogenic bladder. Ganglioside is glycosphingolipids which seems to be involved in the processes of nerve growth, regeneration and tissue reinnervation. The treatment consisted in the daily intramuscular administration of 20 mg ganglioside. Clinical symptoms, vibration sensation and urodynamic studies were recorded at the beginning and 4 weeks later. The clinical responses assessed by subjective complaints and vibration sensation were effective, but no statistically significant difference in urodynamic studies was obtained. Side effects were not observed. In conclusion, ganglioside treatment seems to have a positive effect on diabetic neurogenic bladder.     

Use of a Paracorporeal Pneumatic Ventricular Assist Device for Postoperative Cardiogenic Shock in Two Children with Complex Cardiac Lesions

Pneumatic ventricular assist device (VAD) was utilized for cardiogenic shock after intracardiac operation in two children with complex cardiac anomalies based with single ventricle. In the first case (a 10-year-old), after a modified Fontan operation, VAD was placed between the functional left atrium and ascending aorta, serving as a "artificial single ventricle" with neither pumping chamber nor artificial support in the right side of the heart. The systemic circulation was maintained by keeping relatively high central venous pressure. In another child (a 3-year-old) who underwent repair of incompetent atrioventricular valve leaving intracardiac lesions, VAD was placed between the common atrium and ascending aorta, serving as a pump for both pulmonary and systemic circulation with regulation of pulmonary blood flow through an aortopulmonary Gore-Tex shunt. The circulatory assist with VAD was utilized for 5 and 6 days, respectively. Although weaning from the device was not feasible in both patients because of the pulmonary dysfunction, these experience showed the possible use of VAD for cardiogenic shock after surgery in patients with complex cardiac anomalies.