In vitro response of osteoblast-like and odontoblast-like cells to unsubstituted and substituted apatites

Different types of calcium phosphate compounds [calcium-deficient apatite (CDA); beta-tricalcium phosphate (beta-TCP); biphasic calcium phosphate (BCP)] are commercially available for medical and dental applications as bone substitute materials. Most of the reported in vitro studies on cell-material interactions have used osteoblast-like cells. The purpose of this study was to investigate the in vitro response of osteoblast-like (MC3T3-E1) and odontoblast-like (MDPC23) cells on unsubstituted (HA) and substituted (F-substituted) apatites. MC3T3-E1 and MDPC23 were cultured in alpha-modified medium containing 10% fetal bovine serum, ascorbic acid (50 microg/mL) and beta-glycerophosphate (2 mM). The cells were seeded on pellets made from HA, and FAp (with low, medium, and high F concentrations). Cell morphology was observed after 7 and 14 days using scanning electron microscopy (SEM). Cell attachment and differentiation were determined from the DNA content, alkaline phosphatase (ALP) activity, and total collagen content. Pellet surface composition was characterized by using Fourier Transform infrared spectroscopy. MC3T3-E1 and MDPC23 cells on HA were normal in shape and in fusion but not on FAp. Results of this study showed that the pattern of cell proliferation of osteoblast-like cells was different from that of the odontoblast-like cells. This study suggests that cell morphology, fusion, and proliferation on biomaterial surfaces depend on cell type (osteoblast-like vs odontoblast-like cell) and biomaterial composition (unsubstituted vs substituted F-apatites).     

Differences in the effects of Na+-H+ exchange inhibitors on cardiac function and apoptosis in guinea-pig ischemia-reperfused hearts

The protective effects of the Na+-H+ exchange (NHE) inhibitors SM-198110 (2-[[(aminoiminomethyl) amino] carbonyl]-4-chloro-1H-indole-1-propanesulfonic acid monohydrate) and SM-197378 (N-(aminoiminomethyl)-1-methyl-7-(sulfooxy)-4-(trifluoromethyl)-1H-indole-2-carboxamide monohydrate) were investigated in perfused Langendorff guinea-pig hearts subjected to ischemia (40 min) and reperfusion (40 min). The recovery of left ventricular developed pressure (LVDP) from ischemia by reperfusion was 39.0% in the control, while in the hearts pretreated with SM-198110 or SM-197378 (10(-7) M), it was about 100%. The ATP level, monitored simultaneously by (31)P-nuclear magnetic resonance spectrometry, was already higher than the control value at the end of the ischemic period, and the elevation in Na+ or Ca2+ fluorometric signals induced during ischemia was suppressed. In post-treated hearts, the LVDP recovery rate was significantly higher with SM-198110 than with SM-197378. By in vitro electron paramagnetic resonance spectrometry, SM-197378 was found to directly quench the active oxygen radical, whereas SM-198110 had no effect. Numbers of apoptotic cardiomyocytes after ischemia (1 h) followed by reperfusion (5 h) were significantly lower in SM-197378-treated than in SM-198110-treated hearts, consistent with the level of activity of caspase-3. These results suggest that the antioxidant effects of NHE inhibitors have an important role in apoptosis during ischemia-reperfusion, but apoptosis is not a major manifestation of cardiac function during postischemic recovery, and that NHE-sensitive mechanisms of reperfusion injury promote both necrotic and apoptotic processes death.     

Positive inotropic agents

Despite wide prevalence of beta-blockers and angiotensin-converting enzyme inhibitors for chronic heart failure, their therapeutic efficacy remains limited because effects of these drugs depend largely on pathophysiology of an individual patient. Especially, positive inotropic therapy could be deleterious for some patients, whereas effective in improving symptoms for some patients. Recent clinical experience has led to a concept that in order to be clinically beneficial and safe, positive inotropic agents should only enhance myocardial contractility to a very modest degree in moderately to severely symptomatic patients. Positive inotropic agents could eventually serve as an individualized therapeutic option in effective management of chronic heart failure.     

Mastoid obliteration by BMP-2/collagen composites: an experimental study using tissue engineering

PURPOSE: Several materials have been used in the application of mastoid cavity obliteration during surgery for cholesteatoma; however, nothing has won universal acceptance. Through the advancement of tissue engineering, bone morphogenetic protein-2 (BMP-2)/collagen composites have been elucidated as inducers of heterogenic bone formation. This study was performed to investigate whether these composites are potentially obliteration materials for use in the mastoid cavity by using an animal experimental study. MATERIALS AND METHODS: The composites were implanted in the rat mastoid to investigate whether new bone would be tissue engineered in the mastoid and, if so, whether the newly formed bone was stable. The composites were examined histologically over a 24-week period. RESULTS: The composites implanted in the rat mastoid were able to tissue engineer new bone, and the newly formed bone was stable as assessed histologically, with almost normal bone structure, that was not resorbed during the 24-week period. Adverse immunological reactions were not found during our observation. CONCLUSIONS: Bone that was tissue engineered by the BMP-2/collagen composites was stable as assessed by histological examination and persisted in the rat mastoid. The present study shows that the composites have the potential to become real materials for use in mastoid obliteration.     

Proteasome expression in the skeletal muscles of patients with muscular dystrophy

Previous investigators have suggested that proteolysis by calpain, a Ca²⁺-dependent protease, causes muscle fiber degradation in Duchenne and Becker muscular dystrophies (DMD/BMD). Recent evidence indicates that the nonlysosomal ATP-ubiquitin-dependent proteolytic complex (proteasomes) participates in muscle wasting during various catabolic states and in muscle fiber degradation in physiological or pathological conditions. To elucidate the possible role of proteasomes in dystrophic muscles, routine histochemistry and immunohistochemistry of 26S proteasomes were performed on muscle biopsy specimens obtained from patients with various neuromuscular disorders including DMD/BMD, polymyositis (PM), amyotrophic lateral sclerosis, and peripheral neuropathies, and on normal human muscle specimens. Immunohistochemically, proteasomes were located in the cytoplasm in normal human muscle, but their staining intensity was faint. Compared to control muscles, abnormal increases in both proteasomes and ubiquitin were demonstrated mainly in the cytoplasm of necrotic fibers and to a lesser extent in regenerative fibers in DMD/BMD and PM. Non-necrotic, atrophic fibers in all diseased muscles showed moderate or weak immunoreactions for the proteins; their staining intensities were stronger than those of control muscle fibers. Both proteins often colocalized well. Not all dystrophin-deficient muscle fibers showed a strong reaction for proteasomes. Our results showed increased proteasomes in necrotic and regenerative muscle fibers in DMD/ PMD, although this may not be disease-specific up-regulation. We suggest that the ATP-ubiquitin-dependent proteolytic pathway as well as the nonlysosomal calpain pathway may participate in muscle fiber degradation in muscular dystrophy. Received: 9 July 1999 / Revised: 28 December 1999, 21 February 2000 / Accepted: 21 February 2000     

A cryptic microdeletion including MBD5 occurring within the breakpoint of a reciprocal translocation between chromosomes 2 and 5 in a patient with developmental delay and obesity

The 2q23.1 deletion syndrome has been recently recognized as a neurodevelopmental disorder associated with intellectual disability, epilepsy, and autism spectrum disorder. Recently, methyl‐CpG‐binding domain 5 gene (MBD5), located in the 2q23.1 region, has been considered as a single causative gene of this syndrome. We report on a female patient with a de novo reciprocal translocation between chromosomes 2 and 5. Chromosomal microarray testing revealed a cryptic 896 kb deletion that included MBD5. Although clinical manifestations of this patient are compatible with those of patients with 2q23.1 deletion syndrome, a focal pachygyria revealed by brain magnetic resonance imaging has never been observed in the previously reported cases. Obesity caused by hyperphagia was observed in our patient and 28% of the previously reported patients with the 2q23.1 deletion syndrome. For better medical management, appropriate dietary guidance against hyperphagia should be given to the patients' family. © 2013 Wiley Periodicals, Inc.     

Clinical Response to Systemic Combined Chemotherapy with 5-Fluorouracil and Cisplatin (FP Therapy) in Patients with Advanced Pancreatic Cancer

Pancreatic cancer shows high mortality and has a poor prognosis.Although the rate of response to all chemotherapeutic regimensis low, some patients have shown improvement of their symptomsafter chemotherapy and/or radiotherapy without obvious tumorregression. We assessed the clinical benefit of systemic combinedchemotherapy with 5-fluorouracil and cisplatin (FP therapy)in 21 patients with advanced cancer of the pancreas. The clinicalresponse to FP therapy was evaluated using two parameters: pain(intensity of pain and consumption of morphine) and performancestatus. A patient was considered to be a clinical responderif one of two parameters was positive and the other was positiveor stable. Four patients (19%) responded. Two of the respondersachieved partial response according to the objective tumor response,and the remaining two showed no change. The survival periodin responders was significant longer than in the other patients.The clinical response may be one parameter for evaluating theresults of treatment for pancreatic cancer, and the longer survivalperiod of the clinical responders in this study supports thisnotion.     

A case report of a papillary fibroelastoma arising from the left ventricular outflow septum just beneath the aortic valve

Cardiac papillary fibroelastomas are rare benign tumors with frond-like growths that typically involve the native valve tissue. Papillary fibroelastomas originate less commonly in the ventricular septum. We report a rare case of fibroelastoma arising from the left ventricle.     

Development of collateral circulation after acute myocardial infarction: its role in preserving left ventricular function

The present study evaluated the effects of coronary collateral circulation developing after acute myocardial infarction on global and regional left ventricular function during the chronic stage. The study group consisted of 16 patients with initial myocardial infarction having total occlusion of the proximal left anterior descending coronary artery. To eliminate the effects of collateral circulation existing at the onset of infarction, patients with pre-infarction angina were excluded from this study. The patients were categorized in two groups depending on the extent of their collateral circulation (collateral index: CI 0-3): group A--patients with significant collateral circulation (CI = 2 or 3) to the infarct-related coronary artery; group B--patients without significant collateral circulation (CI = 0 or 1). Their heart rate, left ventricular peak systolic and end-diastolic pressures and cardiac index were similar in the two groups. The left ventricular end-systolic volume index in the group B was significantly greater than that in the group A (60 +/- 21 ml/m2 vs 34 +/- 9 ml/m2, p less than 0.05). Left ventricular ejection fraction in the group A was significantly greater than that of the group B (55 +/- 9% vs 39 +/- 15%, p less than 0.05), and a significant difference was observed in the percentage of segment shortening in the infarct area between the groups A and B (10.8 +/- 9.2% vs -0.2 +/- 5.4%, p less than 0.01). It was concluded that coronary collateral circulation which develops after acute myocardial infarction exerts beneficial effects on global and regional left ventricular function during the chronic stage.