Devices for facial aesthetic improvement in the treatment of skeletal mandibular protrusion

Some techniques for the treatment of mandibular protrusion with consideration for aesthetic improvement of the face as a whole are described. The aesthetic inferiority complex in the mind of patients with masticatory disorders as the chief complaint should not be underestimated. Three techniques were used in this study; preoperative orthodontic treatment, preservation of the patient's self-image, and maintenance of beautiful relationship between the midfacial line and the nasolabial fold as well as the nasal ala.     

Establishment of clonal colony-forming assay system for pancreatic stem/progenitor cells

Pluripotent stem cells found in a number of organs are usually in small cell populations. However, under adaptive stimulation, they enter the stage of growth and differentiation to compensate for the loss of differentiated cells. To analyze stem cell potential precisely, the exclusion of other differentiated cells and a clonal assay system are strongly required. In this study, we established a colony-forming assay system for pancreatic stem/progenitor cells in vitro. In this culture condition, they received signals for growth and differentiation, and formed clonal colonies including pancreatic endocrine-lineage cells, such as alpha and beta cells. By combining this culture system with flow cytometric cell sorting, pancreatic stem/progenitor cells will be enriched, and their potential can be analyzed precisely in single cell-based experiments.     

Targeting Efficiency of Galactosylated Liposomes to Hepatocytes in Vivo: Effect of Lipid Composition

Purpose. To investigate the effects of the lipid composition of galactosylated liposomes on their targeted delivery to hepatocytes. Methods. Several types of liposomes with a particle size of about 90 nm were prepared using distearoyl-L-phosphatidylcholine (DSPC), cholesterol (Chol) and cholesten-5-yloxy-N-(4-((1-imino-2-D-thiogalactosylethyl)amino)butyl)formamide (Gal-C4-Chol), and labeled with [³H]cholesterol hexadecyl ether. Their tissue disposition was investigated in mice following intravenous injection. The binding and internalization characteristics were also studied in HepG2 cells. Results. Compared with [³H]DSPC/Chol (60:40) liposomes, [³H]D-SPC/Chol/Gal-C4-Chol (60:35:5) liposomes exhibit extensive hepatic uptake. Separation of the liver cells showed that galactosylated liposomes are preferentially taken up by hepatocytes, whereas those lacking Gal-C4-Chol distribute equally to hepatocytes and nonparenchymal cells (NPC). Increasing the molar ratio of DSPC to 90% resulted in enhanced NPC uptake of both liposomes, suggesting their uptake via a mechanism other than asialoglycoprotein receptors. DSPC/Chol/Gal-C4-Chol (60:35:5) and DSPC/Chol/Gal-C4-Chol (90:5:5) liposomes exhibited similar binding to the surface of HepG2 cells, but the former were taken up faster by the cells. Conclusions. The recognition of galactosylated liposomes by the asialoglycoprotein receptors is dependent on the lipid composition. Cholesterol-rich galactosylated liposomes, exhibiting less non-specific interaction and greater receptor-mediated uptake, are better for targeting drugs to hepatocytes in vivo.     

Influence of physicochemical properties on pharmacokinetics of non-viral vectors for gene delivery

The influence of physicochemical properties on the in vivo pharmacokinetics of gene delivery vectors after systemic administration is reviewed based on our studies. We have been studying the development of DNA delivery systems, such as plasmid DNA complexed with cationic polymers (polyplexes) and cationic liposomes (lipoplexes). Even if target-recognizable ligand is incorporated into the system, the overall physicochemical properties, notably size and charge, are predominant factors influencing in vivo disposition characteristics of the vector. Based on this consideration, liver cell-specific carrier systems via receptor-mediated endocytosis were successfully developed by optimizing physicochemical characteristics. In conclusion, rational design of gene delivery vectors requires an understanding of their pharmacokinetics in relation to the physicochemical properties. Optimization of the physicochemical properties is important for successful in vivo gene delivery by non-viral vectors.     

Luminal space enlargement by carbachol in rat parotid intralobular ducts

Carbachol (CCh) enlarges the luminal space in rat parotid intralobular ducts, but the mechanism of their enlargement remains obscure. We investigated the involvement of intracellular calcium ions in the enlargement of luminal space by monitoring the luminal space under optical sectioning in a confocal laser scanning microscope using sulforhodamine B. Carbachol increased the intracellular concentration of calcium ions ([Ca2+]i) and the inside diameter without any change in the outside diameter. Removal of extracellular calcium ions modulated CCh-induced changes in [Ca2+]i to transient, but did not markedly inhibit the CCh-induced increase in the inside diameter. Additional loading of BAPTA (1,2-bis (o-aminophenoxy-ethane-n,n,n',n'-tetraacetic acid) in the duct cells suppressed CCh-induced changes. Diphenylamine-2-carboxylate (DPC), but not cytochalasin D, calmodulin inhibitor or nitric oxide synthase inhibitor profoundly suppressed CCh-induced changes. These results suggest that CCh induces enlargement of the luminal space through the activation of DPC-sensitive channels by the release of calcium ions from the intracellular pool.     

Cardiomyocyte transplantation does not reverse cardiac remodeling in rats with chronic myocardial infarction

BACKGROUND: Several reports have documented the potential benefits of cell transplantation as an alternative to cardiac transplantation. This study was designed to investigate whether cardiomyocyte transplantation is effective in rats with chronic myocardial infarction. METHODS: Syngeneic Lewis rats were used in this study. Chronic myocardial infarction was induced in rats by ligating the left anterior descending artery. Four weeks later, after left ventricular (LV) dysfunction with akinetic regions was confirmed by echocardiography, the rats were randomized into two groups: a group that received fetal cardiomyocyte transplantation (TX group; n = 11); and a group that received an intramyocardial injection of culture medium only (control group; n = 12). RESULTS: Four weeks after treatment, the TX group had smaller end-systolic dimension (LVDs) (7.5 +/- 0.9 vs 8.9 +/- 0.8 mm, p < 0.01) and better fractional shortening (FS) (26.2 +/- 5.9 vs 17.7% +/- 5.1%, p < 0.01) than the control group. However, there were no differences in LV end-diastolic dimension, LVDs, and FS between baseline and post-treatment values in the TX group. In addition, plasma levels of atrial natriuretic peptide were not significantly different between the two groups 4 weeks after treatment. In microscopic examination, small amounts of transplanted cardiomyocytes were found only in the periinfarct area, not in the center of scar area, and a thicker ventricular wall in the infarct area was detected in the TX group. CONCLUSIONS: Fetal cardiomyocyte transplantation prevented, but did not reverse, cardiac remodeling that was accompanied with heart failure in myocardial infarction rats. Further investigation is warranted for optimal clinical application to the failing heart.     

Composite arterial Y graft has less coronary flow reserve than independent grafts

BACKGROUND: It is not known whether a composite Y graft of the left internal thoracic artery can provide sufficient blood flow to the whole left coronary system. The aim of this study was to compare regional myocardial blood flow (MBF) and coronary flow reserve after coronary artery bypass grafting using arterial composite Y graft or independent arterial grafts. METHODS: Positron emission tomography was performed at rest and after dipyridamole infusion using oxygen-15-labeled water 2 weeks after coronary artery bypass grafting. Regional MBF was calculated in seven segments of the left ventricle. Coronary flow reserve was defined as the ratio of MBF after dipyridamole infusion to MBF at rest. In the Y graft group (n = 22), a free arterial graft to obtuse marginal arteries was anastomosed to the proximal side of in situ left internal thoracic artery, which was anastomosed to the left anterior descending artery. In the independent graft group (n = 13), left anterior descending and obtuse marginal arteries were independently revascularized using in situ left internal thoracic artery and a free arterial graft. RESULTS: There was no difference between the groups in MBF at rest. Coronary flow reserve in the Y graft group was lower than that in the independent group in the anterobasal (1.43 +/- 0.07 versus 1.90 +/- 0.13, p = 0.038), apical (1.24 +/- 0.06 versus 1.64 +/- 0.12, p = 0.003), septal (1.34 +/- 0.05 versus 1.75 +/- 0.13, p = 0.023), and lateral regions (1.19 +/- 0.04 versus 1.66 +/- 0.09, p = 0.001). CONCLUSIONS: Although arterial composite Y graft improved MBF at rest, it was not as effective as independent grafts for improving coronary flow reserve soon after coronary artery bypass grafting.     

Isolation and transplantation of dopaminergic neurons and neural stem cells

Although transplantation of mesencephalic tissue is considered a promising therapy for Parkinson's disease (PD), its clinical use is still restricted to a very few cases. A major limiting factor of this therapy is the difficulty of obtaining sufficient quantities of viable embryonic mesencephalic tissue. To overcome this limitation, techniques to produce dopaminergic (DA) neurons in vitro have been developed. However, these cultures are likely to contain a variety of unidentified cells, which must be removed before implantation. Specific cell-surface markers to sort DA neurons or their precursors are not available. We have developed an alternative strategy, by which these cells can be labeled with green fluorescent protein and isolated with fluorescent activated cell sorter. Transplantation of the sorted cells resulted in recovery of a rat model of the PD. This strategy should be useful for developing new therapies for PD.     

Metastatic urinary bladder tumor from extragonadal germ cell tumor: a case report

A 37-year old male patient complained of lower back pain. Investigations revealed a retroperitoneal tumor and left-sided cervical lymphadenopathy without abnormal findings in both testicles. The diagnosis of extragonadal germ cell tumor was made based on a lymph node biopsy. Following chemotherapy and retroperitoneal lymphoadenectomy, at outpatient follow-up, beta-HCG elevated again. He complained of gross hematuria, cystoscopy showed a bladder tumor, and abdominal MRI scan showed a right ureteral tumor. Total cystectomy and right nephroureterectomy were performed, which revealed that the bladder and ureteral tumors were metastatic germ cell tumors. Six months later, the patient developed hepatic and mesenteric lymph node metastases that failed to respond to treatment, and died. Germ cell tumors metastasizing to the urinary tract are extremely uncommon, and this is the first report of bladder metastases, other than through direct invasion, from an extratesticular germ cell tumor.     

Association between -1438G/A promoter polymorphism in the 5-HT(2A) receptor gene and fluvoxamine response in Japanese patients with major depressive disorder

Genetic polymorphism of the serotonin 5-HT(2A) receptor seems to be associated with therapeutic response to selective serotonin reuptake inhibitors (SSRIs). The present study investigated whether a novel -1438G/A polymorphism in the promoter region of the 5-HT(2A )receptor gene is associated with therapeutic response to fluvoxamine (an SSRI) in 66 Japanese patients with major depressive disorder. Fluvoxamine (50 to 200 mg) was administered twice daily for 6 weeks. Fifty-four patients completed this study. The genotype distribution and the allele frequencies showed no significant difference between responders and non-responders. The time-course of the Montgomery-Asberg Depression Rating Scale scores showed no significant difference among -1438G/G, -1438G/A, and -1438A/A genotype groups. The results demonstrated that the -1438G/A promoter polymorphism in the 5-HT(2A) receptor gene was unlikely to have a major role in therapeutic response to fluvoxamine in Japanese patients with major depressive disorder.