Evaluation of Facial Soft Tissue in Patients With Cleft Lip and Palate Corrected Using Maxillary Protraction Appliances.

ABSTRACT: Noncontact optical surface scanners have been used to evaluate facial soft tissues. Appropriate evaluation of patients with cleft lip and palate requires comprehensible assessment of the changes in their pre- and post-orthodontic soft tissue and facial growth during chairside assistance. The authors developed a new scanning system that required a shorter measurement time than conventional modalities. The system was implemented on a mannequin and a 6-year-old patient. Seven midfacial landmarks were identified on their faces. The authors measured these landmarks 5 times daily. An experienced orthodontist evaluated and recorded the scores. The scores obtained from the mannequin had a variation of within 0.2 mm, while those obtained from the patient varied within 0.8 mm, except that of the inferior limit of the lips. The study findings suggest that the new laser scanning system can accurately measure facial soft tissue. Further studies should fix patients' head at a definite position for more accurate measurements. An appropriately angled laser sensor would eliminate distortions, thereby increasing the measurement validity.

Up-regulation of protease-activated receptor-1 in diabetic glomerulosclerosis.

Patients with diabetes are under a hypercoagulable state leading to generation of thrombin. It is not known whether thrombin plays a role in the progression of diabetic nephropathy. We analyzed gene expression of two thrombin receptors, protease-activated receptor-1 (PAR-1) and PAR-4 in the kidney of diabetic db/db mice. Mice developed hyperglycemia from 7 to 10 weeks of age and showed renal abnormalities such as mesangial expansion and urinary albumin excretion at 10 weeks of age. PAR-1 mRNA was up-regulated in isolated glomeruli in db/db mice compared with age-matched db/m littermates, but PAR-4 mRNA was not. In situ hybridization studies showed that PAR-1 mRNA was detected mainly at the glomerulus, and that intensive signals were observed in mesangial cells and podocytes. The up-regulation of PAR-1 in glomeruli in diabetic mice may play a role in the progression of glomerulosclerosis and abnormal urinary albumin excretion in diabetic nephropathy.

Mechanism of action of T-705 against influenza virus.

T-705, a substituted pyrazine compound, has been found to exhibit potent anti-influenza virus activity in vitro and in vivo. In a time-of-addition study, it was indicated that T-705 targeted an early to middle stage of the viral replication cycle but had no effect on the adsorption or release stage. The anti-influenza virus activity of T-705 was attenuated by addition of purines and purine nucleosides, including adenosine, guanosine, inosine, and hypoxanthine, whereas pyrimidines did not affect its activity. T-705-4-ribofuranosyl-5'-triphosphate (T-705RTP) and T-705-4-ribofuranosyl-5'-monophosphate (T-705RMP) were detected in MDCK cells treated with T-705. T-705RTP inhibited influenza virus RNA polymerase activity in a dose-dependent and a GTP-competitive manner. Unlike ribavirin, T-705 did not have an influence on cellular DNA or RNA synthesis. Inhibition of cellular IMP dehydrogenase by T-705RMP was about 150-fold weaker than that by ribavirin monophosphate, indicating the specificity of the anti-influenza virus activity and lower level of cytotoxicity of T-705. These results suggest that T-705RTP, which is generated in infected cells, may function as a specific inhibitor of influenza virus RNA polymerase and contributes to the selective anti-influenza virus activity of T-705.

Losartan ameliorates progression of glomerular structural changes in diabetic KKAy mice.

Pathological changes in glomerular structure are typically associated with the progression of diabetic nephropathy. The involvement of angiotensin II (AII) in pathogenesis of diabetic nephropathy has been extensively studied and the therapeutic advantages associated with blockade of renin-angiotensin system (RAS), primarily with angiotensin converting enzyme (ACE) inhibitors, has been well-documented. We studied the effect of RAS blockade with an AII receptor antagonist (losartan) vs. an ACE inhibitor (enalapril) on glomerular lesions in KKAy mice, a model of type 2 diabetes mellitus. Losartan was administered at 3 and 10 mg/kg/day and enalapril at 3 mg/kg/day for 14 weeks in the drinking water. The doses of losartan at 10 mg/kg/day was expected to be equivalent to 3 mg/kg/day of enalapril when considering clinical doses for lowering blood pressure. The dose of 3 mg/kg/day of losartan was selected to compare the efficacy at equivalent dose of enalapril. Histologic observation demonstrated suppression of glomerular mesangial expansion and glomerulosclerosis with exudative lesion in the 10 mg/kg/day losartan group when compared to the untreated diabetic controls. A lesser degree of glomerulosclerosis was also observed with losartan and enalapril treatment at 3 mg/kg/day. Ultrastructural examination of renal glomeruli from the high dose losartan group revealed a decreased degree of effacement and/or irregular arrangement of glomerular podocytic foot process. The beneficial effect of RAS inhibition with the AII receptor antagonist losartan on diabetic glomerular lesions was clearly demonstrated in this study. These findings, therefore, provide mechanistic explanation for the clinical utility of losartan for use in the treatment of diabetic nephropathy in man.

Vitamin D3 up-regulated protein-1 regulates collagen expression in mesangial cells.

BACKGROUND: Hyperglycemia is a known risk factor in the pathogenesis of nephropathy, and collagen accumulation due to an increase reactive oxygen species (ROS) has been suspected to be one of the reasons for high glucose-mediated diseases. However, molecular mechanisms that connect glucose stimulation, oxidative stress, and collagen induction are unknown. METHODS: We examined global changes in gene expression patterns following high glucose stimulation by using DNA microarray technology in cultured human mesangial cells. The expression of vitamin D3 up-regulated protein-1 (VDUP-1), our candidate for the molecular mediator, was evaluated in the human mesangial cells, mouse mesangial cell line, and kidneys of diabetic mice by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Truncated VDUP-1 proteins were used to test the effects of VDUP-1 on the biosynthesis of collagen in mesangial cells. RESULTS: Expression of VDUP-1, which was reported as an inhibitor of thioredoxin, was induced rapidly and constantly after exposure to high concentrations of glucose upon analysis with DNA microarray. Overexpression of VDUP-1 gene in cultured mesangial cells resulted in type IV collagen alpha1 chain (COL4A1) mRNA induction and accumulation of type IV collagen protein. However, induction of COL4A1 expression was abolished with a deletion mutant of VDUP-1, which lost thioredoxin-interacting domain. Also, streptozotocin-induced diabetic mice were shown to overexpress VDUP-1 as well as COL4A1. CONCLUSION: VDUP-1 mediates collagen accumulation in mesangial cells and could be the molecular mediator/marker for fibrosis in diabetic nephropathy caused by chronic hyperglycemia such as diabetes.

Late-onset obesity in mice transgenic for the human renin gene.

We previously generated a strain of transgenic mice carrying the human renin gene, hRN8-12, in the background of C57BL/6j. In this study, we discovered that hRN8-12 male mice, but not females, developed obesity starting at 15 weeks of age. The body weight of 60-week-old male transgenic mice was 2 times higher than that of age-matched wild-type mice. Interestingly, male mice heterozygous for the human renin gene showed moderate weight gain compared with transgenic and wild-type mice. Obese hRN8-12 mice exhibited hyperglycemia, hyperinsulinemia, hyperleptinemia, and hyperlipidemia, and increase in weight in the adipose tissue, liver, heart, and kidneys. Histological analysis demonstrated that fatty hRN8-12 mice developed hypertrophy of pancreatic islets and fatty liver. These results suggested that hRN8-12 mice are associated with obesity dependent on the transgene dosage and should be a genetic model for late-onset obesity.