Effects of ipriflavone on augmented bone using a guided bone regeneration procedure

: This study investigated the effects of ipriflavone (IP) on augmented bone using a guided bone regeneration (GBR) procedure. In 15 rabbits, two titanium caps were placed into calvarial bone for GBR. The animals were divided into three groups: the No-IP (no intake of IP), Post-IP (IP orally, 10 mg/kg/day after GBR), and Pre-IP (IP intake beginning before GBR) groups. One cap was removed from each rabbit after 3 months, and the remaining site was a control. One month after one cap removal, all the animals were euthanized, and histologic and histomorphometric analyses were performed. In all of the groups, the newly generated tissue was of varying size, and it consisted of thin pieces of mineralized bone and large marrow spaces with fat cells and some hematopoietic cells. In all of the control sites, the newly generated tissue was noted and almost filled the space under the cap. There was a significant difference between groups No-IP and Pre-IP (93.8+/-4.6% vs. 98.5+/-0.8%, P<0.05). The tissue generated at the test sites in all of the groups was resorbed, and its original shape and volume were not maintained 1 month after one cap removal. In particular, the greatest percentage, approximately 20% of the newly generated tissue, was resorbed in the No-IP group (93.8+/-4.6% vs. 73.9+/-3.7%, P<0.05), and approximately 11% and 15% in groups Post-IP and Pre-IP, respectively. The relative amount of mineralized bone generated at the control and test sites was significantly larger in groups Post-IP and Pre-IP when compared with group No-IP, except for the test site between groups No-IP and Post-IP (P<0.05). Therefore, the amount of mineralized tissue generated appeared to increase with an increase in the total IP dose. Within the limitations of this rabbit experimental model, we conclude that the daily intake of IP before or after GBR inhibits the resorption of augmented tissue and would be useful for improving the quality of newly generated bone beyond the skeletal envelope.     

Adverse Effects of High Temperature On Mammary Alveolar Development In Vitro

Journal of Mammary Gland Biology and Neoplasia - In the mammary glands during pregnancy, the alveolar buds are first branched from the mammary ducts after which they form the alveolar luminal...     

The superior approach with the stomach roll-up technique improves intraoperative outcomes and facilitates learning laparoscopic distal pancreatectomy: a comparative study between the superior and inferior approach

Surgery Today - We introduced a superior approach and a unique technique to retract the stomach, called the “stomach roll-up technique”, to standardize laparoscopic distal...     

MAOA/B deletion syndrome in male siblings with severe developmental delay and sudden loss of muscle tonus

Deletion of the monoamine oxidase (MAO)-A and MAO-B was detected in two male siblings and in their mother. The approximately 800-kb deletion, extending from about 43.0 MB to 43.8 MB, was detected by array comparative genomic hybridization analysis. The MAOA and MAOB genes were included in the deletion, but the adjacent Norrie disease gene, NDP, was not deleted. The boys had short stature, hypotonia, severe developmental delays, episodes of sudden loss of muscle tone, exiting behavior, lip-smacking and autistic features. The serotonin levels in their cerebrospinal fluid were extremely elevated. Another set of siblings with this deletion was reported previously. We propose recognition of MAOA/B deletion syndrome as a distinct disorder.     

Comparative effects of topiroxostat and febuxostat on arterial properties in hypertensive patients with hyperuricemia

Elevated serum uric acid is a cardiovascular risk factor in patients with hypertension, even when blood pressure (BP) is well controlled. Xanthine oxidoreductase inhibitors (XORi) reduce serum uric acid levels and have several other potential effects. This multicenter, randomized, open‐label study compared the effects of two XORi, topiroxostat and febuxostat, on arterial stiffness, uric acid levels, and BP in hypertensive patients with hyperuricemia. Patients received topiroxostat 40–160 mg/day or febuxostat 10–60 mg/day, titrated to maintain serum uric acid <6 mg/dl, for 24 weeks. The primary endpoint was change in the cardio‐ankle vascular index (CAVI) from baseline to 24 weeks. There were no significant changes in CAVI from baseline to 24 weeks (from 9.13 to 9.16 [feboxustat] and 8.98 to 9.01 [topiroxostat]). Compared with baseline, there were significant reductions in serum uric acid (–2.9 and –2.5 mg/dl; both p < 0.001) and morning home systolic BP (–3.6 and –5.1 mm Hg; both p < 0.01) after 24 weeks'' treatment with febuxostat and topiroxostat. BP decreased to the greatest extent in the subgroup of patients with uncontrolled blood pressure at baseline. Topiroxostat, but not febuxostat, significantly decreased plasma xanthine oxidoreductase activity versus baseline. The urinary albumin‐creatinine ratio (UACR) decreased significantly from baseline to 24 weeks with topiroxostat (–20.8%; p = 0.021), but not febuxostat (–8.8%; p = 0.362). In conclusion, neither topiroxostat nor febuxostat had any significant effects on arterial stiffness over 24 weeks'' treatment.     

Cryopreservation of mobilized blood stem cells at a higher cell concentration without the use of a programmed freezer

Cryopreservation of peripheral blood stem cells (PBSC) mobilized by chemotherapy combined with or without granulocyte colony-stimulating factor (G-CSF) is an essential part of procedure for anti-cancer strategies. We evaluated whether a higher cell concentration (2×10⁸/ml) without the use of a programmed freezer was acceptable for the storage of mobilized PBSC in an autologous setting. Mobilized PBSC were enriched to mononuclear cells (MNC) by Percoll separation and then frozen at cell concentrations of 2–5×10⁷/ml (group I, n=20) or 2×10⁸/ml (group II, n=44) without the use of a programmed freezer using 5% DMSO, 6% hydroxy ethyl starch, and 4% autologous serum or human albumin. CD34+ cells purified by ISOLEX300 were frozen at 2×10⁷/ml (group III, n=22) using the same method. The median recovery rates of CD34+ cells and CFU-GM were, respectively, n.d. (not determined) and 88% in group I, 103 and 64% in group II, and 98 and 53% in group III. There was a statistical significance between the recovery rate of CFU-GM in group III and that in group I (p=0.02). The median percentage of cell viability after thawing in each group was 89, 87, and 75%, respectively. The median numbers of days after PBSCT to achieve a WBC of >1.0×10⁹/l, an absolute neutrophil count of >0.5×10⁹/l, and a platelet count of >50×10⁹/l were, respectively, 11, 11 and 15 in group I; 12, 12 and 16 in group II; and 12, 12 and 27 in group III. These results suggest that enriched MNC from mobilized PBSC could be frozen at a higher cell concentration (2×10⁸/ml) without the use of a programmed freezer, leading to reduction of the toxicities associated with infusion of thawed cells and of costly space required for cell storage.     

Loss of the guide wire: a case report.

A case of a lost guide wire extending from the vena cava to the back of the neck after central venous catheterization is presented. A trainee inserted a central venous catheter via the left subclavian vein in a 40-year-old male patient after surgery, but did not notice that a guide wire was completely inserted in the vein. After 6 months, the lost guide wire was seen extending from the saphenous vein through the vena cava, right atrium, right ventricle, pulmonary artery and lung tissue to the back of neck. Although percutaneous catheterization of central veins is a routine technique, it is a procedure requiring advanced surgical skills, expert supervision, and attention to detail in order to prevent adverse effects. The present case is not only a technological problem, but also one of responsibility. The operator must hold onto the guide wire at all times until removal from the vessel, and a supervisor must make sure that trainees are aware of all possible complications.     

Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, attenuates myocardial ischemia-reperfusion injury in mice with metabolic disorders

Although considerable attention has focused on obesity, insulin resistance and abnormal lipid metabolism as coronary risk factors, it remains unclear how these pathogenic factors affect the inflammatory response after myocardial ischemia-reperfusion. This study was conducted to evaluate whether these metabolic disorders exacerbate myocardial ischemia-reperfusion injury, and to determine if ischemia-reperfusion injury could be modified with the thiazolidinedione, pioglitazone. Experiments were performed in KK-A^y and C57BL/6J mice subjected to 40 min of ischemia followed by reperfusion. Infiltration of inflammatory cells in ischemic myocardium, and infarct size 3 days after reperfusion were significantly higher in KK-A^y than C57BL/6J mice (p < 0.05 and p < 0.001, respectively). Furthermore, expression of chemokines, inflammatory cytokines and extracellular matrix proteins in ischemic myocardium was significantly higher in KK-A^y than C57BL/6J mice 1 day after reperfusion. Pioglitazone treatment of KK-A^y mice for 14 days significantly reduced the accumulation of inflammatory cells in ischemic myocardium, and infarct size 3 days after reperfusion compared to vehicle treatment (p < 0.05 and p < 0.05, respectively). Pioglitazone also attenuated expression of chemokines, inflammatory cytokines and extracellular matrix proteins in ischemic myocardium 1 day after reperfusion. In vitro experiments demonstrated that tumor necrosis factor-α (TNF-α) was significantly higher in cultured peritoneal macrophages from KK-A^y than C57BL/6J mice, and pioglitazone significantly reduced TNF-α in macrophages from both types of mice. These findings suggest that metabolic disorders exacerbate ischemia-reperfusion injury as a result of overexpression of inflammatory mediators, and this effect might be improved, in part by the anti-inflammatory effects of pioglitazone.     

Circulating advanced glycation end products (AGEs) and soluble form of receptor for AGEs (sRAGE) are independent determinants of serum monocyte chemoattractant protein-1 (MCP-1) levels in patients with type 2 diabetes

BACKGROUND: Atherosclerosis is an inflammatory disease. Monocyte chemoattractant protein-1 (MCP-1) is an essential chemokine responsible for the recruitment of monocytes to inflammatory lesions in the vasculature, an initial step of atherosclerosis. Since serum levels of MCP-1 are higher in patients with type 2 diabetes, inhibition of MCP-1 may be a novel therapeutic target for prevention of accelerated atherosclerosis in diabetes. However, little is known about the regulation and determinants of serum MCP-1 levels in patients with diabetes. In this study, we examined the determinants of serum MCP-1 levels in type 2 diabetic patients. METHODS: Eighty-six consecutive outpatients with type 2 diabetes (36 male and 50 female; mean age 68.4+/-9.6) underwent a complete history and physical examination, determination of blood chemistries, MCP-1, tumour necrosis factor-alpha, adiponectin, advanced glycation end products (AGEs), and soluble form of receptor for AGEs (sRAGE). We examined the association between MCP-1 levels and those in anthropometric, metabolic and inflammatory variables in these subjects. RESULTS: Univariate regression analysis showed that serum levels of MCP-1 were positively associated with AGEs (r=0.386, p<0.001) and sRAGE (r=0.315, p<0.001). After adjusting for age and sex, AGEs (p<0.001) and sRAGE (p<0.05) still remained significant. CONCLUSION: The results demonstrate for the first time that circulating levels of AGEs and sRAGE are independent determinants of serum MCP-1 levels in patients with type 2 diabetes. Our present observations suggest the AGEs-RAGE system may be mainly involved in the elevation of MCP-1 in type 2 diabetic patients.     

Serum heart-type fatty acid binding protein predicts cardiac events in elderly patients with chronic heart failure

BACKGROUND AND OBJECTIVES: Heart-type fatty acid binding protein (H-FABP) is released into the circulation from the damaged myocardium of patients with severe chronic heart failure. Chronic heart failure is the most frequent cause of death and disability in the elderly. However, there are no data for the prognostic value of H-FABP in the elderly population. This study investigated whether H-FABP can effectively predict the prognosis in elderly patients (> or = 70 years) with chronic heart failure. METHODS: Serum H-FABP levels were measured in 90 chronic heart failure patients > or =70 years old (mean age 77 +/- 4 years, range 70-92 years), and patients were followed-up for 421 +/- 326 days. RESULTS: There were 35 cardiac events (38.9%) including cardiac deaths and readmissions for worsening chronic heart failure. Multivariate analysis with the Cox proportional hazard model showed that H-FABP was the only independent predictor of cardiac events (chi2 = 6.640, p = 0.0100). Kaplan-Meier analysis revealed that H-FABP effectively risk stratified elderly patients with chronic heart failure for cardiac events. CONCLUSIONS: These findings suggest that H-FABP is a reliable marker for prognosis in elderly patients with chronic heart failure.