Genetic factors associated with elevation of uric acid after treatment with thiazide-like diuretic in patients with essential hypertension.

We investigated changes in blood pressure (BP) and metabolic adverse effects, especially elevation of uric acid (UA), after treatment with a thiazide-like diuretic (TD) in patients with essential hypertension. Furthermore, the role of genetic factors in the elevation of UA by TD was assessed by a 500 K SNP DNA microarray. The subjects included 126 hypertensive patients (57 women and 69 men, mean age 59 ± 12 years) who registered for the GEANE (Gene Evaluation for ANtihypertensive Effects) study. After one month of the nontreatment period, TD, indapamide, angiotensin II receptor antagonist valsartan, and Ca channel blocker amlodipine were administered to all patients for 3 months each in a randomized crossover manner. BP, renal function, serum UA level, and electrolytes were measured at baseline and at the end of each treatment period. Single nucleotide polymorphisms (SNPs) associated with UA elevation after treatment with indapamide were investigated by a genome-wide association study (GWAS). Indapamide significantly decreased both office and home BP levels. Treatment with indapamide also significantly reduced the estimated glomerular filtration rate and serum potassium and increased serum UA. Patients whose UA level increased more than 1 mg/dl showed significantly higher baseline office SBP and plasma glucose and showed greater decline in renal function compared with those who showed less UA increase (<1 mg/dl). Some SNPs strongly associated with an increase in UA after treatment with indapamide were identified. This study is the first report on SNPs associated with UA elevation after TD treatment. This information may be useful for the prevention of adverse effects after treatment with TD.

Irradiation effects of low temperature multi gas plasma jet on oral bacteria.

The purpose of this study is to evaluate the sterilization effects of a newly developed low temperature multi gas plasma jet on oral pathogenic microorganisms (Streptococcus mutans [S. mutans], Lactobacillus fermentum [L. fermentum], Aggregatibacter actinomycetemcomitans [A. actinomycetemcomitans]). Plasma gas which generated from O2, N2, Ar and 50% (O2+N2) was irradiated to the microbes. Effect of O2 plasma irradiation on S. mutans under scanning electron microscopy (SEM) was also observed. O2 plasma was directly applied to dental plaque on human extracted tooth. Then, the depth of enamel resorption area was noted by nanoscale hybrid microscope. O2 had the best sterilizing effect for all microbes. The potent bactericidal effect of plasma irradiation was also observed by SEM. Decalcification of enamel was noted significantly lower in plasma irradiated tooth surface compared to no plasma exposure group. These findings revealed that multi gas plasma jet has great potential to be used for dental treatment.

A case of tooth autotransplantation after long-term cryopreservation using a programmed freezer with a magnetic field.

This case report describes the treatment of a skeletal Class III malocclusion with autotransplantation of a cryopreserved tooth. To gain an esthetic facial profile and good occlusion, extraction of bimaxillary premolars and surgical therapy were chosen. The patient had chronic apical periodontitis on the lower left first molar. Although she did not feel any pain in that region, the tooth was considered to have a poor prognosis. Therefore, we cryopreserved the extracted premolars to prepare for autotransplantation in the lower first molar area because the tooth would probably need to be removed in the future. The teeth were frozen by a programmed freezer with a magnetic field (CAS freezer) that was developed for tissue cryopreservation and were cryopreserved in -150°C deep freezer. After 1.5 years of presurgical orthodontic treatment, bilateral sagittal split ramus osteotomy was performed for mandible setback. Improvement of the facial profile and the occlusion were achieved in the retention phase. Six years after the initial visit, the patient had pain on the lower left first molar, and discharge of pus was observed, so we extracted the lower left first molar and autotransplanted the cryopreserved premolar. Three years later, healthy periodontium was observed at the autotransplanted tooth. This case report suggests that long-term cryopreservation of teeth by a CAS freezer is useful for later autotransplantation, and this can be a viable technique to replace missing teeth.

Effects of pulpectomy on the amount of root resorption during orthodontic tooth movement.

INTRODUCTION: Previous studies have revealed that orthodontic force affects dental pulp via the rupture of blood vessels and vacuolization of pulp tissues. We hypothesized that pulp tissues express inflammatory cytokines and regulators of odontoclast differentiation after excess orthodontic force. The purpose of this study was to investigate the effects of tensile force in human pulp cells and to measure inflammatory root resorption during tooth movement in pulpless rat teeth. METHODS: After cyclic tensile force application in human pulp cells, gene expression and protein concentration of macrophage colony-stimulating factor, receptor activator of nuclear factor kappa-B ligand, interleukin-1 beta, and tumor necrosis factor alpha were determined by real-time polymerase chain reaction and enzyme-linked immunoassay. Moreover, the role of the stretch-activated channel was evaluated by gadolinium (Gd(3+)) treatment. The upper right first molars of 7-week Wistar rats were subjected to pulpectomy and root canal filling followed by mesial movement for 6 months. RESULTS: The expression of cytokine messenger RNAs and proteins in the experimental group peaked with loading at 10-kPa tensile force after 48 hours (P < .01). Gd(3+) reduced the expression of these cytokine messenger RNAs and protein concentrations (P < .01). The amount of inflammatory root resorption was significantly larger in the control teeth than the pulpectomized teeth (P < .05). CONCLUSIONS: This study shows that tensile forces in the pulp cells enhance the expression of various cytokines via the S-A channel, which may lead to inflammatory root resorption during tooth movement. It also suggests that root canal treatment is effective for progressive severe inflammatory root resorption during tooth movement.

Genome-wide response to antihypertensive medication using home blood pressure measurements: a pilot study nested within the HOMED-BP study.

BACKGROUND: Patients with mild-to-moderate essential hypertension in the HOMED-BP trial were randomly allocated to first-line treatment with a calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB). METHODS: We recruited 265 (93 for CCB, 71 for ACEI and 101 for ARB) patients who completed the genomic study. Home blood pressure was measured for 5 days off-treatment before randomization and for 5 days after 2-4 weeks of randomized drug treatment. Genotyping was performed by 500K DNA microarray chips. The blood pressure responses to the three drugs were analyzed separately as a quantitative trait. For replication of SNPs with p < 10(-4), we used the multicenter GEANE study, in which patients were randomized to valsartan or amlodipine. RESULTS: SNPs in PICALM, TANC2, NUMA1 and APCDD1 were found to be associated with CCB responses and those in ABCC9 and YIPF1 were found to be associated with ARB response with replication. CONCLUSION: Our approach, the first based on high-fidelity phenotyping by home blood pressure measurement, might be a step in moving towards the personalized treatment of hypertension.

Cryopreservation of rat MSCs by use of a programmed freezer with magnetic field.

Mesenchymal stem cells (MSCs) can be used for the regeneration of various tissues and cryopreservation of MSCs is so important for regenerative medicine. The purpose of this study was to evaluate the influences of cryopreservation on MSCs by use of a programmed freezer with a magnetic field (CAS freezer). MSCs were isolated from bone marrow of rat femora. The cells were frozen by a CAS freezer with 10% dimethyl sulfoxide (Me2SO) and cryopreserved for 7 days at a temperature of -150 °C. Immediately after thawing, the number of survived cells was counted. The cell proliferation also examined after 48 h culture. Next, MSCs were frozen by two different freezers; CAS freezer and a conventional programmed freezer without magnetic field. Then, osteogenic and adipogenic differentiations of cryopreserved cells were examined. As a result, survival and proliferation rates of MSCs were significantly higher in CAS freezer than in the non-magnetic freezer. Alizarin positive reaction, large amount of calcium quantification, and greater alkaline phosphatase activity were shown in both the non-cryopreserved and CAS groups after osteogenic differentiation. Moreover, Oil Red O staining positive reaction and high amount of PPARγ and FABP4 mRNAs were shown in both the non-cryopreserved and CAS groups after adipogenic differentiation. From these findings, it is shown that a CAS freezer can maintain high survival and proliferation rates of MSCs and maintain both adipogenic and osteogenic differentiation abilities. It is thus concluded that CAS freezer is available for cryopreservation of MSCs, which can be applied to various tissue regeneration.

Gummy smile and facial profile correction using miniscrew anchorage.

This case report describes the treatment of a case involving a skeletal Class II facial profile with a gummy smile. While treating a facial profile and a gummy smile, the outcome may not always be successful with orthodontic therapy alone. For this reason, surgical therapy is often chosen to gain an esthetic facial profile and a good smile. However, sometimes the patients reject surgical treatment and an alternative method must be considered. Skeletal anchorage systems such as miniscrews are now frequently used for correcting severe malocclusion that should be treated by surgical therapy. In this case report, we treated a skeletal Class II malocclusion with a convex profile and a gummy smile using miniscrews, which were placed in the upper posterior and anterior areas. The active treatment period was 3.5 years, and the patient's teeth continued to be stable after a retention period of 36 months.

In-vitro and in-vivo study of periodontal ligament cryopreserved with a magnetic field.

INTRODUCTION: The purpose of this study was to examine the effect of a new cryopreservation method with a magnetic field on periodontal regeneration in vitro and in vivo. METHODS: Human periodontal ligament cells were frozen in 10% dimethyl sulfoxide by using a programmed freezer with a magnetic field. Cells were cryopreserved for 3 days at -150°C. Immediately after thawing, collagen type I and alkaline phosphatase gene expression were determined by real-time polymerase chain reaction. Incisors were extracted from 15-week-old Wistar rats and cryopreserved or dried for 3 days. Then the incisors were replanted into the same sockets. Ninety days after transplantation, they were observed under light microscopy. RESULTS: There was no difference in the messenger RNA expression of collagen type I between the cryopreserved and the control groups. The expression of alkaline phosphatase messenger RNA in the cryopreserved group was slightly decreased compared with the control group. There was no progressive root resorption in the teeth that were replanted immediately (control group) or cryopreserved. However, there was widespread root resorption and ankylosis in the dried teeth. CONCLUSIONS: These results show that a magnetic field programmed freezer can be successfully used for cryopreservation of teeth.

Treatment of a case of skeletal class II malocclusion with temporomandibular joint disorder using miniscrew anchorage.

At the present time, there are no reports in the literature on the treatment of temporomandibular joint disorder (TMD) by intrusion of molars using mini-screws. This case report describes the treatment for a female patient, aged 19 years seven months, with a TMD and an excessive lower anterior facial height. Overjet and overbite were +5.0 mm and +0.5 mm, respectively. The patient had a history of orthodontic treatment in which her first premolars were all extracted. During the first orthodontic treatment, a clockwise mandibular rotation was observed as a result of the increase of posterior dentoalveolar height. She had temporomandibular joint (TMJ) pain during mouth opening and complained of difficulty in eating due to masticatory dysfunction. The pretreatment Schuller views of both TMJ showed a posterior condyle position. In order to correct the overjet, molar relationship and the mandibular condyle position, a miniscrew was inserted into the palatal region of the upper first molar to intrude the upper posterior teeth. As the upper molars were intruded, the overjet was decreased, and a class I molar relationship was achieved by a counterclockwise mandibular rotation. After one year of treatment, an acceptable occlusion was achieved, and the condyle moved into centric position in the glenoid fossa. The patient's teeth continued to be stable, and she had no pain in TMJ after a retention period of three years. The result of this treatment showed that molar intrusion using miniscrew anchorage is effective for treatment of a TMD patient with a posterior condyle position.

Efficacy of low-density lipoprotein apheresis in arteriosclerosis obliterans of the lower extremities: two cases with marked alleviation of clinical symptoms.

We have recognized marked effectiveness for intermittent claudication with low-density lipoprotein (LDL) apheresis in two cases of arteriosclerosis obliterans (ASO). The Case 1 was a 73-year-old man with intermittent claudication of both lower extremities (Fontaine class II), digital subtraction angiography (DSA) revealed complete obstruction of the left common iliac artery, formation of a collateral to the peripheral portion of the left common iliac artery, and diffuse stenosis of the peripheral portion of the right common iliac artery. Ten sessions of LDL apheresis (LDL-A) improved the walking distance from 100 m before to 600 m after LDL-A treatment. The Case 2 was a 61-year-old man with intermittent claudication of the left lower extremity (walking distance: 200 m) began at 59 years. DSA revealed diffuse stenosis of the peripheral portion of the left popliteal artery. Ten sessions of LDL-A improved the walking distance from 200 m before to 800 m after LDL-A. At one month after the end of LDL-A treatment, DSA revealed formation of collateral to the peripheral portion of the left popliteal artery. Our findings suggest that LDL-A combined with drug treatment is safe and useful for the treatment of ASO, especially walking distance improved with short term treatment.

Comparison between cilnidipine and amlodipine besilate with respect to proteinuria in hypertensive patients with renal diseases.

Unlike other dihydropyridine calcium channel blockers (CCBs), cilnidipine has been reported to exert an N-type calcium-channel-blocking activity and to reduce sympathetic hyperactivity. This study compared cilnidipine and amlodipine with respect to their effects on renal function and proteinuria. Twenty-eight proteinuric hypertensive outpatients (13 men and 15 women, aged 62+/-2 years) who had been maintained on CCBs for more than 3 months were randomly assigned to a group receiving amlodipine besilate (14 patients) or a group receiving cilnidipine (14 patients). CCBs were increased in dosage or other drugs were added until blood pressure decreased below 140/90 mmHg, but no inhibitors of the renin-angiotensin (RA) system were added or changed in dosage. Before and at 6 and 12 months after randomization, the concentrations of urine protein, urine albumin, serum and urine creatinine (Cr), and serum beta2-microglobulin were determined. The amlodipine group showed a significant increase in proteinuria, while the increase was suppressed in the cilnidipine group. The rate of increase in proteinuria at 12 months was 87% (95% confidence interval (CI) -10 to 184) of the baseline value with amlodipine and 4% (95% CI -69 to 77) of baseline with cilnidipine, a significant intergroup difference (p<0.05). The mean blood pressure remained in the 96-99 mmHg range until 12 months after randomization, showing no significant difference between the two groups. The cilnidipine group showed an increase in serum Cr levels (baseline vs. 12 months, 1.36+/-0.20 vs. 1.50+/-0.23 mg/dl, p<0.01). Overall, an inverse correlation existed between the changes in Cr and proteinuria (r= -0.477, p<0.01). These results suggest that cilnidipine results in a greater suppression of the increase in proteinuria and greater reduction in glomerular filtration rate than amlodipine, and that these effects are similar between cilnidipine and RA inhibitors. However, additional large-cohort and longer-term studies will be needed to clarify whether cilnidipine is superior to other CCBs in maintaining renal function.

Effects of repeated alcohol intake on blood pressure and sodium balance in Japanese males with hypertension.

Alcohol consumption causes biphasic changes in blood pressure (BP) in Asians. The aim of the present study was to investigate the effects of repeated alcohol intake on BP and sodium metabolism. Fourteen Japanese males with hypertension (37-67 years old) were examined under standardized conditions (Na intake 120 mmol/day). After 1 week of alcohol restriction, the patients consumed a control drink with dinner for 3 days, 1 ml/kg of alcohol for the next 7 days, then the control drink for 3 days. Supine BP and heart rate were measured 5 times daily, and urinary excretion of water and sodium was determined throughout the study period. Average BP decreased initially, then returned to the baseline level during the alcohol period. Evening BP decreased significantly throughout the alcohol period, although the reduction was attenuated during the late phase. Morning and afternoon BP did not change significantly, but tended to be elevated during the late phase. Heart rate increased both in the morning and evening during the alcohol period. Urine volume did not change during the early phase, but increased significantly during the late phase. Urinary sodium excretion decreased initially, but increased during the middle phase of the alcohol period. In conclusion, BP decreases initially with sodium retention, then returns to the baseline level with restoration of sodium balance during repeated alcohol intake in Japanese males with hypertension. Sodium retention during the early phase appears to be the consequence of BP reduction and may contribute to the subsequent changes in BP.

Changes in C-reactive protein plasma levels during low-density lipoprotein apheresis.

C-reactive protein (CRP) is one of the important risk factors for atherosclerosis, and its serum level is lowered by popular cholesterol-lowering drugs, statins. This study was undertaken to examine the changes of CRP levels during dextran-sulfate (DS) low-density lipoprotein (LDL) apheresis. In 15 apheresis sessions in seven patients with severe hypercholesterolemia (four men and three women, aged between 36 and 70 years), changes in CRP levels were examined. The efficiency in adsorption of CRP with DS column was evaluated by measuring CRP levels in both pre- and post-column plasma. In one patient, the effect of repeated apheresis sessions on CRP preapheresis levels was examined. The changes in interleukin (IL)-6 plasma levels were also examined in six sessions. Although IL-6 levels after 3,000 mL-plasma treatment rose to 170% of preapheresis levels, CRP levels decreased significantly (from 1.91 +/- 0.49 mg/L to 0.89 +/- 0.24, P < 0.01). C-reactive protein was almost completely adsorbed by the DS column and CRP preapheresis levels were decreased gradually by repetition of apheresis. CRP, a novel risk factor of atherosclerosis, was effectively removed by DS-LDL apheresis. The decrease in CRP plasma levels may be involved in prevention of atherosclerotic vascular diseases due to DS-LDL apheresis.

Peristent tissue proliferation of multilink stents is dependent on preprocedural plaque area: a serial intravascular ultrasound analysis.

It is not known whether any factors are related to tissue proliferation within and surrounding stents in humans. The authors used serial intravascular ultrasound (IVUS) to evaluate the relationship between IVUS parameters and tissue proliferation within and surrounding Multilink stents. They were able to analyze preinterventional and postinterventional and follow-up IVUS studies in 33 native vessel lesions in 33 patients with stable angina pectoris. Quantitative coronary angiography and IVUS measurements were performed before and after intervention and at follow-up. IVUS imaging using an automatic transducer pullback device allowed follow-up analysis of the same lesion site. The vessel area at the lesion site increased from 17.1 +/- 4.5 mm2 after intervention to 18.5 +/- 5.9 mm2 at follow-up (p<0.01). The in-stent tissue growth (after intervention to follow-up) in-stent plaque area (PA) was 1.6 +/- 1.1 mm2, and the peristent tissue growth (after intervention to follow-up) peristent PA was 0.8 +/- 2.3 mm2. In multivariate analysis, the preprocedural PA at the lesion site was the best predictor of the peristent tissue growth, whereas no factors predicted the in-stent tissue growth. Risk factors, clinical characteristics, and quantitative coronary angiographic parameters showed no relation to the peristent tissue growth or the in-stent tissue growth. The peristent tissue growth was closely related to the preprocedural plaque size, while the factors that affect the in-stent tissue growth were not identified.

Primary cardiac lymphoma--a case report.

Primary cardiac lymphoma, which is very rare, is generally regarded to have a poor prognosis. A case of a 69-year-old man with primary cardiac lymphoma diagnosed by antemortem examination is reported. A computed tomography scan of the chest demonstrated a huge right atrial mass with invasion into the other chambers. No mediastinal lymphadenopathy was detected. Cytologic analysis of pericardial effusion revealed diffuse large B-cell type non-Hodgkin malignant lymphoma. The patient died on the 18th day of chemotherapy (cyclophosphamide, hydroxydaunomycin, oncovin, and prednisone) due to low-output syndrome and multiple organ failure. At autopsy, massive gray-white tumor almost occupied the right atrium and invaded the right inferior lobe of the lung. Although prognosis of primary cardiac lymphoma remains poor, early diagnosis may improve the prognosis.