The gingival crevicular fluid levels of growth factors in patients with amlodipine-induced gingival overgrowth: A pilot study.

BACKGROUND: Amlodipine, calcium channel blocker (CCB), is used in the management of cardiovascular diseases which causes gingival overgrowth (GO). The growth factors may have a role in the pathogenesis of amlodipine-induced GO. OBJECTIVES: This pilot study aimed to investigate the growth factors including transforming growth factor-b1 (TGF-b1), platelet-derived growth factor-BB (PDGF-BB), and basic fibroblast growth factor (bFGF) in gingival crevicular fluid (GCF) of patients with amlodipine-induced GO and compare with of healthy subjects. METHODS: GCF samples were collected from 56 sites presenting GO (GO + group) and from 38 sites not presenting GO (GO- group) of 5 patients using amlodipine for more than one year, and from 45 sites (control group) of 5 healthy subjects. The levels of TGF-b1, PDGF-BB, and bFGF were determined by using ELISA kits. RESULTS: The mean concentration of TGF-b1 in GCF samples of GO + group (9.50 ± 7.30 ng/ml) was higher than both GO- group (2.07 ± 0.50 ng/ml) and control group (2.74 ± 1.01 ng/ml) (P = 0.014). No significant difference was found among the groups in the GCF levels of PDGF-BB (P = 0.767). bFGF was detected in only 33% of the sites from patients. CONCLUSION: These preliminary results suggest that TGF-b1 may play a crucial role in the pathogenesis of amlodipine-induced GO.

Peri-operative delineation of non-melanoma skin cancer margins in vivo with handheld reflectance confocal microscopy and video-mosaicking.

BACKGROUND: The surgical removal of non-melanoma skin cancers (NMSCs) is guided by the pathologic examination of margins. However, the preparation of histopathology is time consuming, labour-intensive and requires separate laboratory infrastructure. Furthermore, when histopathology indicates positive margins, patients must return for re-excisions. Reflectance confocal microscopy (RCM) with a new video-mosaicking approach can noninvasively delineate margins directly on patients and potentially guide surgery in real-time, augmenting the traditional approaches of histopathology. OBJECTIVE: To assess a new peri-operative RCM video-mosaicking approach for comprehensive delineation of NMSC margins on patients in vivo. METHODS: Thirty-five patients undergoing Mohs micrographic surgery (MMS) in the Mohs surgery unit at Memorial Sloan Kettering Cancer Center, New York, NY were included in the study. RCM imaging was performed before and after the first staged excision by acquiring videos along the surgical margins (epidermal, peripheral and deep dermal) of each wound, which were subsequently processed into video-mosaics. Two RCM evaluators read and assessed video-mosaics, and subsequently compared to the corresponding Mohs frozen histopathology. RESULTS: Reflectance confocal microscopy videos and video-mosaics displayed acceptable imaging quality (resolution and contrast), pre-operatively in 32/35 (91%) NMSC lesions and intra-operatively in 29/35 lesions (83%). Pre-operative delineation of margins correlated with the histopathology in 32/35 (91%) lesions. Intra-operative delineation correlated in 10/14 (71%) lesions for the presence of residual tumour and in 18/21 (86%) lesions for absence. Sensitivity/specificity were 71%/86% and 86%/81% for two RCM video-mosaic evaluators, and overall agreement was 80% and 83% with histopathology, with moderate inter-evaluator agreement (k = 0.59, P ≤ 0.0002). CONCLUSIONS: Peri-operative RCM video-mosaicking of NMSC margins directly on patients may potentially guide surgery in real-time, serve as an adjunct to histopathology, reduce time spent in clinic and reduce the need for re-excisions. Further testing in larger studies is needed.

The effects of N-acetylcysteine on cisplatin induced cardiotoxicity.

OBJECTIVES: Recent studies reported that oxidative stress is an important mechanism that contributes to cisplatin induced cardiotoxicity. In the present study, the effects of N-acetylcysteine (NAC), which is an antioxidant, on cisplatin induced cardiotoxicity were investigated in a rat model. METHODS: Thirty two rats were separated into 4 equal groups: Control, NAC-250, CP (cisplatin), CP+NAC. Rats in the experimental groups were treated with a single dose of cisplatin intraperitoneally (ip) (10 mg/kg) and NAC (ip, 250 mg/kg) for 3 consecutive days. At the end of the experiment, cardiotoxicity was determined from plasma CK-MB, LDH, cTnI and cardiac myosin light chain-1 (CMLC-1) levels. In the tissue samples, total oxidant capacity (TOC), total antioxidant capacity (TAC), lipid hydroperoxide (ROOH) and thiol levels were measured. The hearts were also analyzed histopathologically. RESULTS: It was determined that cisplatin increased the tissue TOC, ROOH levels and decreased TAC and thiol levels. NAC administration after cisplatin treatment was observed to have ameliorated histological and functional changes in heart. CONCLUSIONS: In conclusion, the results of this experimental study suggested that oxidative stress had a serious effect on cisplatin cardiotoxicity, and NAC could be used as a therapeutic agent in addition to standard cisplatin treatment protocols (Tab. 3, Fig. 1, Ref. 35).

Unsupervised delineation of stratum corneum using reflectance confocal microscopy and spectral clustering.

BACKGROUND: Measuring the thickness of the stratum corneum (SC) in vivo is often required in pharmacological, dermatological, and cosmetological studies. Reflectance confocal microscopy (RCM) offers a non-invasive imaging-based approach. However, RCM-based measurements currently rely on purely visual analysis of images, which is time-consuming and suffers from inter-user subjectivity. METHODS: We developed an unsupervised segmentation algorithm that can automatically delineate the SC layer in stacks of RCM images of human skin. We represent the unique textural appearance of SC layer using complex wavelet transform and distinguish it from deeper granular layers of skin using spectral clustering. Moreover, through localized processing in a matrix of small areas (called 'tiles'), we obtain lateral variation of SC thickness over the entire field of view. RESULTS: On a set of 15 RCM stacks of normal human skin, our method estimated SC thickness with a mean error of 5.4 ± 5.1 µm compared to the 'ground truth' segmentation obtained from a clinical expert. CONCLUSION: Our algorithm provides a non-invasive RCM imaging-based solution which is automated, rapid, objective, and repeatable.

Morphology and morphometry of the human embryonic brain: A three-dimensional analysis.

The three-dimensional dynamics and morphology of the human embryonic brain have not been previously analyzed using modern imaging techniques. The morphogenesis of the cerebral vesicles and ventricles was analyzed using images derived from human embryo specimens from the Kyoto Collection, which were acquired with a magnetic resonance microscope equipped with a 2.35-T superconducting magnet. A total of 101 embryos between Carnegie stages (CS) 13 and 23, without apparent morphological damage or torsion in the brain ventricles and axes, were studied. To estimate the uneven development of the cerebral vesicles, the volumes of the whole embryo and brain, prosencephalon, mesencephalon, and rhombencephalon with their respective ventricles were measured using image analyzing Amira™ software. The brain volume, excluding the ventricles (brain tissue), was 1.15 ± 0.43 mm(3) (mean ± SD) at CS13 and increased exponentially to 189.10 ± 36.91 mm(3) at CS23, a 164.4-fold increase, which is consistent with the observed morphological changes. The mean volume of the prosencephalon was 0.26 ± 0.15 mm(3) at CS13. The volume increased exponentially until CS23, when it reached 110.99 ± 27.58 mm(3). The mean volumes of the mesencephalon and rhombencephalon were 0.20 ± 0.07 mm(3) and 0.69 ± 0.23 mm(3) at CS13, respectively; the volumes reached 21.86 ± 3.30 mm(3) and 56.45 ± 7.64 mm(3) at CS23, respectively. The ratio of the cerebellum to the rhombencephalon was approximately 7.2% at CS20, and increased to 12.8% at CS23. The ratio of the volume of the cerebral vesicles to that of the whole embryo remained nearly constant between CS15 and CS23 (11.6-15.5%). The non-uniform thickness of the brain tissue during development, which may indicate the differentiation of the brain, was visualized with surface color mapping by thickness. At CS23, the basal regions of the prosencephalon and rhombencephalon were thicker than the corresponding dorsal regions. The brain was further studied by the serial digital subtraction of layers of tissue from both the external and internal surfaces to visualize the core region (COR) of the thickening brain tissue. The COR, associated with the development of nuclei, became apparent after CS16; this was particularly visible in the prosencephalon. The anatomical positions of the COR were mostly consistent with the formation of the basal ganglia, thalamus, and pyramidal tract. This was confirmed through comparisons with serial histological sections of the human embryonic brain. The approach used in this study may be suitable as a convenient alternative method for estimating the development and differentiation of the neural ganglia and tracts. These findings contribute to a better understanding of brain and cerebral ventricle development.

Demographical, laboratory and associated findings in patients with perniosis.

BACKGROUND: Perniosis is a cold-induced inflammatory disorder of the acral areas. The objective of this study was to investigate the demographic characteristics, associated factors, clinical and laboratory findings in patients with perniosis and to compare those findings between patients who had recurrent and acute disease. METHODS: Thirty-four patients with perniosis were investigated retrospectively for age, gender, occupation, smoking and diet histories, associated diseases, family history of perniosis, precipitating factors, the month of onset and the duration of perniosis, the distribution of the lesions and the results of laboratory investigations. RESULTS: Fifteen patients were male and 19 were female. The ages of the patients ranged from 15 to 57 years. Thirteen patients were working as sales people, which was the most common occupation. Sixteen patients were smokers. While 25 of the patients had encountered perniosis for the first time, in 9 of the patients, there were recurrent lesions. Diseases other than perniosis were recorded in 6 of the patients. The laboratory tests revealed mild leukopenia in 2, antinuclear antibody (ANA) positivity in 3, mild rise in albumin level in serum protein electrophoresis in 1 patient. ANA positivity was significantly higher in patients with recurrent disease. CONCLUSION: Perniosis was more common in women and below 40 years. We found no significant laboratory findings except ANA positivity in patients with recurrent perniosis.

Thymidylate synthase genotype and serum concentrations of homocysteine and folate in Behçet's disease.

The aim of this study was to assess whether thymidylate synthase (TYMS) genotype, serum homocysteine, and folate concentrations were related to venous thrombosis in Behçet's disease (BD) patients. The study included 104 BD patients fulfilling the International Study Group Criteria for the diagnosis of BD and 121 healthy individuals-controls. Out of 104 patients, 50 (48%) had vascular involvement: 34 had active-history of venous thrombosis, 16 had arterial involvement (aneurysm), and 11 of these patients had both venous and arterial lesions as confirmed by Doppler ultrasound and/or angiography. Genotype analysis of the TYMS promoter enhancer region was determined by polymerase chain reaction. The distribution of the TYMS genotypes 2R/2R, 2R/3R, 3R/3R, 4R/2R, and 3R/3R were not significantly different between BD patients and control group (p>0.05; 16.5% vs 8.3%, 49.0% vs 53.9%, 31.7% vs 38.0%, 1.9% vs 0%, and 1.0% vs 0%, respectively). TYMS genotypes were not associated with thrombosis and serum homocysteine concentration in BD patients. The mean serum homocysteine level in patients with thrombosis (14.87+/-8.99 micromol/L) was significantly higher than the level in patients without thrombosis (10.78+/-3.81 micromol/L; p<0.05). Serum folate concentrations were not different between the BD patients and the healthy controls. The study results suggest that the distribution TYMS genotype in BD was not different from that of healthy controls. There was no relationship between TYMS genotype and the homocysteine levels in BD patients with thrombosis or without thrombosis.

Thyroid Hormone Withdrawal Further Exacerbates Oxidative Stress in Patients with Thyroid Carcinoma.

PURPOSE: Hypothyroidism has profound effects on multiple organs and systems including cellular oxidative damage. Thus, we aimed to investigate the effects of acute hypothyroidism on oxidative stress in patients with differentiated thyroid carcinoma (DTC). PATIENTS: 33 patients with DTC were involved in the study. 23 healthy subjects matched for age and body mass index (BMI) served as control group. Fasting blood sample was obtained for the determination of blood chemistry, lipids, myeloperoxidase (MPO) activity, total lipid hydroperoxide (LHP), pyrrolized protein, protein carbonyl compounds (PCC), advanced oxidation protein products (AOPP) and thiol levels before and after thyroid hormone withdrawal (THW) in patients with DTC. RESULTS: MPO activity, total LHP, pyrrolized protein, PCC and AOPP levels were significantly higher, but thiol levels were significantly lower in patients with DTC while on L-thyroxine treatment than those of healthy subjects. At acute hypothyroid status after THW, MPO activity, total LHP, pyrrolized protein, PCC and AOPP levels further increased, thiol levels further decreased in patients with DTC as compared to healthy subjects and to their on L-thyroxine treatment period. CONCLUSIONS: This study showed an increased oxidative stress in patients with DTC which is further exacerbated with acute hypothyroidism upon THW. This situation may have treatment implications such as antioxidant therapy, at least during THW.

Three-dimensional morphology of the human embryonic brain.

The morphogenesis of the cerebral vesicles and ventricles was visualized in 3D movies using images derived from human embryo specimens between Carnegie stage 13 and 23 from the Kyoto Collection. These images were acquired with a magnetic resonance microscope equipped with a 2.35-T superconducting magnet. Three-dimensional images using the same scale demonstrated brain development and growth effectively. The non-uniform thickness of the brain tissue, which may indicate brain differentiation, was visualized with thickness-based surface color mapping. A closer view was obtained of the unique and complicated differentiation of the rhombencephalon, especially with regard to the internal view and thickening of the brain tissue. The present data contribute to a better understanding of brain and cerebral ventricle development.

The effects of dialyzer reuse on plasma antioxidative mechanisms in patients on regular hemodialysis treatment.

The effects of antioxidative mechanism are known to be reduced in patients on regular hemodialysis treatment (RHT). The data about the effects of reuse on antioxidative mechanisms are limited. Twelve patients on RHT (age range: 16-50 years) were included in the study. The basal and after 4 months of dialyzer reuse period, plasma antioxidant activity (AOA), myeloperoxidase (MPO) activity, ceruloplasmin (Cp), copper (Cu), transferrin (TF), and sulphydryl group (SH) levels were detected. The basal plasma AOA (110.92 +/- 17.19 microliters), TF (1.23 +/- 0.23 g/l), and SH (307.11 +/- 51.81 mumol/l) levels were lower than the levels of the control subjects (73.75 +/- 9.07 microliters, 2.38 +/- 0.25 g/l, 690.59 +/- 84.18 mumol/l) (p < .001). The basal Cp (0.47 +/- 0.08 g/l) and MPO activity (86.31 +/- 9.57 U/l) levels were higher than the levels of the control subjects (0.34 +/- 0.07 g/l and 65.90 +/- 7.28 U/l) (p < .001). The basal Cu levels (1.19 +/- 0.24 mg/l) were similar to the levels of the control subjects (1.11 +/- 0.13 mg/l) (p > .05). The difference between plasma AOA (83.33 +/- 14.71 microliters), Cp (0.38 +/- 0.08 g/l), and MPO activity (64.43 +/- 10.01 U/l) after the reuse period and the control values were not statistically significant (p > .05). The TF (1.87 +/- 0.15 g/l) levels after the reuse period were significantly lower than the control values (p < .001), although the levels were increased after the reuse period. Our findings may indicate some beneficial effects of hemodialyzer reuse process on plasma antioxidative mechanisms in patients on RHT.

Real-time image reconstruction and display system for MRI using a high-speed personal computer.

A real-time NMR image reconstruction and display system was developed using a high-speed personal computer and optimized for the 32-bit multitasking Microsoft Windows 95 operating system. The system was operated at various CPU clock frequencies by changing the motherboard clock frequency and the processor/bus frequency ratio. When the Pentium CPU was used at the 200 MHz clock frequency, the reconstruction time for one 128 x 128 pixel image was 48 ms and that for the image display on the enlarged 256 x 256 pixel window was about 8 ms. NMR imaging experiments were performed with three fast imaging sequences (FLASH, multishot EPI, and one-shot EPI) to demonstrate the ability of the real-time system. It was concluded that in most cases, high-speed PC would be the best choice for the image reconstruction and display system for real-time MRI.

The evaluation of lipid peroxidation and adenosine deaminase activity in patients with Behçet's disease.

OBJECTIVE: Despite unknown etiology, immunologic alterations and neutrophil hyperfunctions may be involved in the etiopathogenesis of Behçet's Disease (BD). The purpose of the study was to investigate whether adenosine deaminase (ADA) activity, accepted as a nonspecific marker of T lymphocyte activation, may have a potential role in BD, and also may be related to the production of reactive oxygen species (ROS) by neutrophils. DESIGN AND METHODS: ADA activities and malondialdehyde (MDA; endproduct of lipid peroxidation induced by ROS) levels in both plasma and erythrocytes were spectrophotometrically measured in 25 patients with BD and also in 25 healthy controls. RESULTS: ADA activity was found to be higher in plasma, but lower in erythrocytes; plasma and erythrocyte MDA levels were higher in BD patients than those of controls. In addition, plasma ADA activity was positively related to MDA levels in both plasma (p < 0.05) and erythrocytes (p < 0.01). There was also positive correlation between MDA levels (p < 0.05), but negative correlations between ADA activities (p < 0.01) and also between ADA and MDA values in erythrocytes (p < 0.01) of BD patients. CONCLUSION: These findings may provide some evidence for a potential role of T lymphocyte activation in BD as reflected by increased plasma ADA activity, and for the presence of possible interrelationship between activated T cells and neutrophil hyperfunctions, such as ROS generation, as reflected by increased MDA levels.

Oxidative enzymes of polymorphonuclear leucocytes and plasma fibrinogen, ceruloplasmin, and copper levels in Behçet's disease.

This study was performed to investigate the antioxidant mechanisms of polymorphonuclear leucocytes (PMN) in active stage of Behçet's Disease. PMN activities of myeloperoxidase (p < 0.02), superoxide dismutase (p < 0.001), catalase (p < 0.005), and glutathione peroxidase (p < 0.005) were significantly lower in the patients: the NADPH oxidase activity was significantly higher (p < 0.001) than those in controls. The plasma levels of ceruloplasmin (Cp), fibrinogen, and copper (Cu) were also significantly higher in the patients group (p < 0.001). Significant and positive correlations were found between the glutathione peroxidase and catalase activities (p < 0.001) and also between the plasma Cp and Cu levels (p < 0.001) in the patients group. However, no correlation was observed among the other enzyme activities. In the control group, a significantly positive correlation was present only between the plasma ceruloplasmin and Cu levels (p < 0.001). It was concluded that (impaired PMN functions) decreased enzyme activities in the antioxidant system and increased levels of oxygen free radicals may play a role in tissue damage in Behçet's disease.

Oxidative stress in hemodialyzed patients and the long-term effects of dialyzer reuse practice.

OBJECTIVES: To investigate the existence of an altered oxidant/ antioxidant balance in patients on regular hemodialysis treatment (RHT) and whether there is any effect of dialyzer reuse on oxidative damage and antioxidative mechanism. DESIGN AND METHODS: Malondialdehyde (MDA) levels and glutathione peroxidase (GPx) activities in both plasma and erythrocytes, plasma selenium (Se) levels, and erythrocyte superoxide dismutase (SOD) activities of RHT patients were determined at the beginning and end of 4-month reuse period. RESULTS: When compared to healthy controls, both plasma and erythrocyte MDA levels were found to be significantly higher in RHT patients before the dialyzer reuse practice; whereas both plasma and erythrocyte GPx activities, erythrocyte SOD activity, and also plasma Se levels were lower in the same patient group than those of controls. When statistical comparison was made on RHT patients between before and after the reuse period, the decreases in MDA levels but increases in the enzyme activities and also an increase in plasma Se levels were observed after the reuse period. However, erythrocyte SOD activities and plasma Se levels measured after the reuse period were not found to be statistically different from the control values; MDA levels still remained elevated above the control values, and GPx activities were not attained to those of controls, after the reuse practice. In addition, positive correlations were found between activities of erythrocyte SOD and GPx enzymes, between GPx and Se levels and negative correlations between the activities of both enzymes and MDA levels in erythrocytes of patients on RHT. CONCLUSION: These findings may indicate that dialyzer reuse may provide, at least partly, an improvement on oxidative stress in patients on RHT.

Image reconstruction algorithm for single-photon-emission computed tomography with uniform attenuation.

A new method is presented for obtaining an analytical solution to the image-reconstruction problem in single-photon-emission computed tomography. The rigorous solution is introduced by applying an analytical continuation process to the two-dimensional Fourier transform of the image, which is derived from the one-dimensional Fourier transforms of projection functions. The calculations can be carried out in a short computation time without involving unstable procedures. Numerical simulations were made to demonstrate the effectiveness of the proposed method.

Changes in platelet monoamine oxidase and plasma dopamine-beta-hydroxylase activities in lithium-treated bipolar patients.

The activity of monoamine oxidase (MAO) and dopamine-beta-hydroxylase (DBH), enzymes involved in monoamine metabolism, were studied in 29 bipolar patients (mean age = 33.12 years, SD = 7.27) who were treated with lithium carbonate and in 20 healthy volunteers (mean age = 30.05 years, SD = 6.04). Platelet MAO activity was higher after lithium withdrawal, whereas plasma DBH activity was lower in remitted euthymic bipolar patients compared with normal volunteers. During lithium treatment, platelet MAO activity decreased and plasma DBH activity increased compared with the lithium-withdrawal values. It was also observed that the activities of these enzymes in the bipolar patients during lithium treatment did not differ from those in the volunteers. Thus, platelet MAO and plasma DBH activities differed in unmedicated patients with bipolar affective disorder from those of healthy subjects. Treatment with lithium appeared to have a normalizing effect on MAO and DBH activity levels.

Development of a 1.0 T MR microscope using a Nd-Fe-B permanent magnet.

A compact 1.0 T MR microscope was developed using a permanent magnet made of high performance Nd-Fe-B magnetic material and a compact MRI console (54 cm (W) x 77 cm (H) x 60 cm (D), 80 kg weight). Since the magnetic field of the permanent magnet had a large temperature coefficient (-1200 ppm/deg), an internal NMR locking technique was developed for the imaging sequences. The performance of the system was evaluated using several biological specimens. As a result, good SNR 3D images at (50 microm)(3)-(200 microm)(3) voxel dimensions were obtained in practical imaging times (0.5-7.5 hours). Thus we have concluded that the permanent-magnet compact MR microscope has great promise as a research or analytical tool.

Architecture of baked breads depicted by a magnetic resonance imaging.

The architecture of baked breads made of fresh dough and frozen dough was depicted by magnetic resonance imaging (MRI). Pieces of bread (16 mm cubic cakes) were soaked in organic solvents containing various concentrations of heavy metals (Cu(2+), Co(2+) and Fe(3+)) and images of the grain structure of the breads were obtained. Of the organic solvents tested, acetone was preferable because of its single peak that prevents chemical shift effects on images, the retention of the bread structure, and the solubility of heavy metals. The heavy metals, especially Fe(3+), shortened the overly long relaxation times of acetone to practical lengths for imaging and stained the materials to provide high contrasts. The images obtained in acetone with 8 mM Fe(3+) were suitable for analyzing crumb grain structures. The bread of fresh dough showed a uniform distribution of pores of various sizes made of thin gluten sheets, whereas the pores in the bread of frozen dough were less, prominently large, non-uniformly distributed, and made of thick gluten sheets.

Contraceptive steroids increase erythrocyte lipid peroxidation in female rats.

In order to investigate the effects of contraceptive steroid combinations on lipid peroxidation in the erythrocyte membranes, adult female rats were divided into 2 groups for short- and long-term investigations; each group was then subdivided into 5 subgroups according to orally given low and high doses of EE/NEA (ethinyl estradiol/norethisterone acetate) and EE/LNG (ethinyl estradiol/levonorgestrel) combinations and control group. Since EE was included in each combination, the groups were named according to the progestin (NEA, LNG) components. At the end of the experiment periods, lipid peroxidation in the erythrocyte membranes from rats was measured. When compared to the controls, except low-dose LNG groups, lipid peroxidation levels were increased in all study groups. It was seen that the effect of NEA and LNG combinations on lipid peroxidation was not time-, but dose-dependent. When these combinations were compared to each other, different effects of NEA and LNG on lipid peroxidation were not detected in the experiment period. As a result, the increased lipid peroxidation following the administration of contraceptive steroid combinations is a very important finding that should be taken into account, in addition to the effects of these steroids on lipid and lipoprotein metabolism.