Evidence of an Off-Resonant Electronic Transport Mechanism in Helicenes.

Helical molecules have been proposed as candidates for producing spin-polarized currents, even at room conditions, due to their chiral asymmetry. However, describing their transport mechanism in single molecular junctions is not straightforward. In this work, we show the synthesis of two novel kinds of dithia[11]helicenes to study their electronic transport in break junctions among a series of three helical molecules: dithia[n]helicenes, with n = 7, 9, and 11 molecular units. Our experimental measurements and clustering-based analysis demonstrate low conductance values that remain similar across different applied voltages and molecules. Additionally, we assess the length dependence of the conductance for each helicene, revealing an exponential decay characteristic of off-resonant transport. This behavior is primarily attributed to the misalignment between the energy levels of the molecule-electrodes system. The length dependence trend described above is supported by ab initio calculations, further confirming an off-resonant transport mechanism.

Unraveling the Interplay between Quantum Transport and Geometrical Conformations in Monocyclic Hydrocarbons' Molecular Junctions.

In the field of molecular electronics, especially in quantum transport experiments, determining the geometrical configurations of a single molecule trapped between two electrodes can be challenging. To address this challenge, we employed a combination of molecular dynamics (MD) simulations and electronic transport calculations based on density functional theory to determine the molecular orientation in our break-junction experiments under ambient conditions. The molecules used in this study are common solvents used in molecular electronics, such as benzene, toluene (aromatic), and cyclohexane (aliphatic). Furthermore, we introduced a novel criterion based on the normal vector of the surface formed by the cavity of these ring-shaped monocyclic hydrocarbon molecules to clearly define the orientation of the molecules with respect to the electrodes. By comparing the results obtained through MD simulations and density functional theory with experimental data, we observed that both are in good agreement. This agreement helps us to uncover the different geometrical configurations that these molecules adopt in break-junction experiments. This approach can significantly improve our understanding of molecular electronics, especially when using more complex cyclic hydrocarbons.

Serum sonic hedgehog (SHH) and interleukin-(IL-6) as dual prognostic biomarkers in progressive metastatic breast cancer.

Serum from one hundred and ten breast cancer patients and thirty healthy female volunteers, were prospectively collected and evaluated for serum levels of Shh and IL-6 using human Shh and IL-6 specific enzyme-linked immunoassays. All patients were regularly monitored for event free survival (EFS) and overall survival (OS). Overall outcome analysis was based on serum Shh and IL-6 levels. In patients with progressive metastatic BC, both serum Shh and IL-6 concentrations were elevated in 44% (29 of 65) and 63% (41 of 65) of patients, respectively, at a statistically significant level [Shh (p = 0.0001) and IL-6 (p = 0.0001)] compared to the low levels in healthy volunteers. Serum levels tended to increase with metastatic progression and lymph node positivity. High serum Shh and IL-6 levels were associated with poor EFS and OS opposite to the negative or lower levels in serum Shh and IL-6. The elevated levels of both serum Shh and IL-6 were mainly observed in BC patients who had a significantly higher risk of early recurrence and bone metastasis, and associated with a worse survival for patients with progressive metastatic BC. Further studies are warranted for validating these biomarkers as prognostic tools in a larger patient cohort and in a longer follow-up study.

Prognostic factors for cervical spondylotic amyotrophy: are signs of spinal cord involvement associated with the neurological prognosis?

OBJECTIVES: The purpose of this study was to clarify the prognostic factors for cervical spondylotic amyotrophy (CSA). METHODS: The authors retrospectively reviewed the medical records of 47 consecutive patients with CSA in whom the presence/absence of the pyramidal tract sign was noted. We analyzed whether the age, sex, presence of diabetes mellitus, medication (vitamin B12), type of the most atrophic and impaired muscle, the muscle strength at the presentation, the presence of the pyramidal tract sign, magnetic resonance imaging (MRI) findings, including the presence and number of T2 high signal intensity areas (T2 HIA) in the spinal cord and the conversion to surgery were associated with the recovery of muscle strength in the patients. In addition, we also investigated whether the duration of symptoms before surgery and the type of surgery were associated with the recovery of muscle strength in patients who required conversion to surgical treatment. RESULTS: The presence of T2 HIA on MRI (P=0.002), the number of T2 HIA on MRI (P=0.002) and conversion to surgery (P=0.015) were found to be significantly associated with a poorer recovery at the observational final follow-up. Further, the presence of the pyramidal tract sign (P=0.043) was significantly associated with a poor recovery at the final follow-up after surgery. CONCLUSION: The presence of a high signal intensity change on T2-weighted MRI and the pyramidal tract sign can be used as prognostic factors for patients with CSA.

High Dose Cytosine Arabinoside in the consolidation of adult acute myeloid leukemia.

This interventional study was done to evaluate the duration of remission with High Dose Cytosine Arabinoside (Ara-C) as post-remission chemotherapy in the consolidation of adult acute myeloid leukemia. A total of 32 patients were included in this study. Among them, 19 were male and 13 were female and the age of the patients ranges from 15-60 years. We use High Dose Cytosine Arabinoside 1.5-2.5 g/m2 i.v, 12 hourly, over 2-3 hours on day 1, 3 and 5 in a 28 days cycle. This study was done during the period of April 2007 to March 2009 in the department of hematology, Dhaka Medical College & Hospital. History, clinical features and laboratory investigations were included. Among 32 patients, 5 patients (15.6%) received one cycle, 20 patients (62.5%) received two cycles and 7 patients (21.9%) received three cycles. The mean ± SD duration of remission (disease free survival) was 5.20 ± 3.83 months who received one cycle, 9.55 ± 3.30 months and 10.71 ± 1.70 months who received two cycles and three cycles respectively. The adverse effects of the therapy were neutropenia and neutropenic fever, purpuric rash, gum bleeding, mucositis and peripheral neuropathy. The supportive materials needed were antibiotics (both prophylactic and treatment) 86.13%, blood and blood products 51.7% and G-CSF 14.9% patients of all cycles. High Dose Ara-C (HiDAC) is a safe and cost effective consolidation treatment for AML patients in complete remission. This therapy merits multi-center control study to define its efficacy and cost-effectiveness in contrast to our socio-economic condition.

Dental caries area of rat molar expanded by cigarette smoke exposure.

OBJECTIVES: Passive smoking is the involuntary inhalation of cigarette smoke (CS) and has an adverse impact on oral health. We examined the effect of CS exposure on caries risk and experimental dental caries. METHODS: Experimental dental caries was induced in rat maxillary molars which were inoculated orally with Streptococcus mutans MT8148 and maintained on a cariogenic diet (diet 2000) and high sucrose water during the experimental period. CS-exposed rats were intermittently housed in an animal chamber with whole-body exposure to CS until killed. Whole saliva was collected before CS exposure (day 0) and for 30 days after the start of CS exposure. Saliva secretion was stimulated by administration of isoproterenol and pilocarpine after anesthesia. Maxillary molars were harvested on day 31. RESULTS: The increase in body weight of the CS-exposed rats was less than that of the control rats. Salivary flow rate, concentration of S. mutans in the stimulated saliva and caries activity score did not significantly differ between 0 and 30 days after the start of CS exposure. Histological examination of the caries-affected area on maxillary molars 30 days after CS exposure showed expansion compared to control rats. In the electron probe microanalysis, no differences were observed between the mineral components of the CS-exposed teeth and the control teeth. CONCLUSION: These results suggest that CS exposure expands the caries-affected area in the maxillary molars of the rat.

Therapy for nifedipine-induced gingival overgrowth by Saireito in rats.

OBJECTIVE: A calcium antagonist, nifedipine, causes gingival overgrowth as a side effect. It has been confirmed that the Japanese traditional medicine, Saireito, inhibits the nifedipine-induced proliferation of gingival fibroblasts in vitro. We performed an in vivo experiment to determine whether Saireito has a therapeutic use in the treatment of nifedipine-induced gingival overgrowth. METHODS: The rats had significant gingival overgrowth induced by the administration of nifedipine. The space between the submandibular incisors and the width of buccal gingiva of maxillary left first molar were macroscopically measured. The buccal gingiva was microscopically examined. RESULTS: Eight weeks after Saireito was administrated together with nifedipine, Saireito decreased both the incisor space and the gingiva width which had been enlarged by nifedipine and furthermore, the area of connective tissue of nifedipine + Saireito group was significantly smaller than that of nifedipine alone. CONCLUSION: In conclusion, Saireito may be clinically effective in therapy for calcium antagonist-induced gingival overgrowth.

Macrolide antibiotics like azithromycin increase lipopolysaccharide-induced IL-8 production by human gingival fibroblasts.

OBJECTIVE: Macrolide antibiotics are reported to modulate the production of cytokines in various type of cells. We examined the effect of macrolide antibiotics on inflammatory cytokines (IL-6 and IL-8) and chemical mediator (PGE(2)) and also matrix metalloproteinases (MMPs) productions by human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS). METHODS: The effect of macrolide antibiotics [erythromycin (EM), azithromycin (AZM) and josamycin (JOM)] on HGFs proliferation were examined by MTT assay. HGFs were treated with LPS from Porphyromonas gingivalis (PgLPS) and macrolide antibiotics, and IL-6, IL-8 and PGE(2) levels were evaluated by ELISA. MMPs were detected by gelatin zymography. RESULTS: AZM slightly but significantly decreased HGFs proliferation, while EM and JOM did not affected. AZM increased PgLPS-induced IL-8 production dose-dependently, while AZM did not alter IL-6 and PGE2 productions. EM and JOM did not altered PgLPS-induced IL-6, IL-8 and PGE(2) productions. All macrolide antibiotics did not alter MMPs production. These results indicate that macrolide antibiotics have no direct anti-inflammatory effect. However, the use of the inhibitors of cell signaling pathway failed to reveal the mechanism that AZM enhanced PgLPS-induced IL-8 production. CONCLUSION: These results suggest macrolide antibiotics have an indirect anti-inflammatory effect as a result of their antimicrobial properties. Because AZM increased LPS-induced IL-8 production by HGFs, the possibility is considered that neutrophils may be migrated to periodontal tissue and phagocytize the periodontopathic bacteria more efficiently.

The effects of cigarette exposure on rat salivary proteins and salivary glands.

OBJECTIVE: Passive smoking is the involuntary inhalation of cigarette smoke (CS) and has an adverse impact on oral health. We examined the effect of CS exposure on saliva and salivary glands (SGs). METHODS: Cigarette smoke-exposed rats were intermittently housed in an animal chamber with whole-body exposure to CS until killed. Whole saliva was collected before CS exposure (0 day), and 15 and 30 days after the start of CS exposure. Saliva secretion was stimulated by administration of isoproterenol and pilocarpine after anesthesia. SGs were collected on 31 days. RESULTS: The increase in body weight of the CS-exposed rats was less than that of the control rats. Salivary flow rates did not differ at 0, 15 or 30 days after the start of CS exposure. However, the amylase and peroxidase activities and total protein content in the saliva were significantly lower in 15-day CS-exposed rats than in 15-day control rats. Histological examination of the SGs of CS-exposed rats showed vacuolar degeneration, vasodilation and hyperemia. CONCLUSION: These results suggest that CS exposure has adverse impacts on salivary composition and SGs, which could aggravate the oral environment.

The effects of antibiotics on in vitro biofilm model of periodontal disease.

OBJECTIVE: Periodontal disease is considered to be a bio?film infectious disease. The effects of macrolide and tetracycline on biofilm were examined in in vitro biofilm model made of periodontal disease-associated bacteria. METHODS: Biofilms were made on salivary pellicle by adding Streptococcus gordonii for 2 days, followed by Porphyromonas gingivalis inoculation for 2, 5, or 12 days. Biofilms were treated with macrolide antibiotics; erythromycin (EM), azithromycin (AZM) and josamycin (JOM) and tetracycline antibiotic, minocycline (MINO). The effects of these antibiotics on biofilms were examined using colorimetric quantification method, scanning electron microscope (SEM) and confocal laser scanning microscopy (CLSM). RESULTS: When antibiotics were added to the biofilm 2 days after inoculation of Porphyromonas gingivalis (biofilm inhibition model), all four antibiotics decreased the number of bacteria by both colorimetric method and SEM observation. When antibiotics were added to biofilms 5 or 12 days after inoculation (biofilm destruction model), those in biofilms were decreased by EM and AZM compared with JOM and MINO. Moreover, CLSM observation demonstrated that EM and AZM killed bacteria in biofilm more deeply than JOM and MINO. CONCLUSION: These results suggest the feasibility of EM and AZM for the treatment of periodontal disease as a biofilm infectious disease.

Ultrasound monitoring of temperature change in liver tissue during laser thermotherapy: 10 degrees C intervals.

In thermal tissue ablation, it is very important to control the increase in the temperature for having an efficient ablation therapy. We conducted this study to determine the efficacy of measuring pixel shift of ultrasound B-mode images as a function of change in tissue temperature. By fixing some micro thermocouples in liver tissues, temperature at different points was monitored invasively in vitro during laser-induced thermotherapy. According to our results optimum power and exposure time were determined for ultrasound temperature monitoring. Simultaneously, noninvasive temperature monitoring was performed with ultrasound B-mode images. These images were saved on computer from 25 degrees C to 95 degrees C with 10 degrees C steps. The speed of sound changes with each 10 degrees C temperature change that produce virtual shifts in the scatter positions. Using an image processing method, the pixel shift due to 10 degrees C temperature change was extracted by motion detection. The cubic regression function between the mean pixel shifts on ultrasound B-mode images caused by the change in speed of sound which in turn was a function of the mean change in temperature was evaluated. When temperature increased, pixel shift occurs in ultrasound images. The maximum pixel shift was observed between 60 to 70 degrees C. After 70 degrees C, the local pixel shift due to change in the speed of sound in liver tissue had an irregular decreasing. Pearson correlation coefficient between invasive and non-invasive measurements for 10 degrees C temperature changes was 0.93 and the non-linear function was suitable for monitoring of temperature. Monitoring of changes in temperature based on pixel shifts observed in ultrasound B-mode images in interstitial laser thermotherapy of liver seems a good modality.

Global Distribution and Density of Constructed Impervious Surfaces.

We present the first global inventory of the spatial distribution and density ofconstructed impervious surface area (ISA). Examples of ISA include roads, parking lots,buildings, driveways, sidewalks and other manmade surfaces. While high spatialresolution is required to observe these features, the new product reports the estimateddensity of ISA on a one-km² grid based on two coarse resolution indicators of ISA - thebrightness of satellite observed nighttime lights and population count. The model wascalibrated using 30-meter resolution ISA of the USA from the U.S. Geological Survey.Nominally the product is for the years 2000-01 since both the nighttime lights andreference data are from those two years. We found that 1.05% of the United States landarea is impervious surface (83,337 km²) and 0.43 % of the world's land surface (579,703km²) is constructed impervious surface. China has more ISA than any other country(87,182 km²), but has only 67 m² of ISA per person, compared to 297 m² per person in theUSA. The distribution of ISA in the world's primary drainage basins indicates that watersheds damaged by ISA are primarily concentrated in the USA, Europe, Japan, China and India. The authors believe the next step for improving the product is to include reference ISA data from many more areas around the world.

Feasibility of using collagen as the base of the antifungal drug, miconazole.

The feasibility of using collagen as the base of miconazole was investigated. The addition of 33% collagen to a miconazole solution did not affect the minimal inhibitory concentration (MIC80) of the miconazole solution for Candida albicans. When 1 microg mL(-1) of miconazole in 33% collagen solution was plated on resin discs and dried to yield a thin membrane, the growth of C. albicans on the resin discs was nearly completely inhibited. In addition, we compared the antifungal effect of this collagen solution that contained 1 microg mL(-1) miconazole, with the antifungal effect of miconazole gel that had been diluted with glycerol (the main component of miconazole gel) to yield a final concentration of 1 microg mL(-1) of miconazole; as a result, we found that the collagen solution containing 1 microg mL(-1) miconazole had a stronger antifungal effect. In conclusion, our results demonstrated that it may be feasible to use collagen as the base of miconazole instead of glycerol, and suggest that a collagen-based miconazole solution would have a stronger antifungal effect than commercially available miconazole gel. Collagen-based miconazole solution may be useful for the treatment of Candida-associated denture stomatitis.

Participation of tyrosine kinase and phospholipase Cgamma in isradipine-induced proliferation of cultured human gingival fibroblasts.

Some kinds of drugs such as calcium (Ca(2+)) channel antagonists, antiepileptics and immunosuppressants cause gingival overgrowth as a side effect, the mechanism of which is still unclear. We have examined the effects of isradipine, one of the dihydropyridine-derivative Ca(2+) channel antagonists, on cultured human gingival fibroblast Gin-1 cells. In the present study, to elucidate the mechanism by which isradipine causes gingival overgrowth, we examined whether tyrosine kinase (TK) and phopholipase Cgamma (PLCgamma) are involved in the isradipine-induced proliferation of gingival fibroblasts. Herbimycin A (1 microM) remarkably inhibited the isradipime (10 microM)-induced proliferation. Both U73122 (5 microM), a PLCgamma inhibitor, and xestospongin C (5 microM), an antagonist of a receptor of inositol 1,4,5-trisphosphate in Ca(2+) stores, significantly reduced the [Ca(2+)]i raised by isradipine (10 microM). Thus, the findings obtained here indicate that TK and PLCgamma are closely involved in the isradipine-induced [Ca(2+)]i rise to elicit gingival overgrowth.

Membrane type 1-matrix metalloproteinase expression is regulated by E-cadherin through the suppression of mitogen-activated protein kinase cascade.

To elucidate the role of E-cadherin in matrix metalloproteinases (MMPs) expression, we transfected to squamous carcinoma cells with E-cadherin cDNA. HN5 cells and mock-transfected HN5-neo cells expressed proMMP-2 and active MMP-2. E-cadherin-transfected HN5-EC cells produced comparable proMMP-2 but low active MMP-2; and membrane type 1-MMP (MT1-MMP) mRNA declined. Phosphorylated ERK, a marker of mitogen-activated protein (MAP) kinase cascade, also declined in HN5-EC cells. The addition of anti-E-cadherin antibody resulted in the disappearance of these alterations in HN5-EC cells. These results suggest that E-cadherin suppresses MAP kinase cascade and down-regulates MT1-MMP.

Determination of imbalance between MMP-2 and TIMP-2 in human neuroblastoma by reverse-transcription polymerase chain reaction and its correlation with tumor progression.

BACKGROUND/PURPOSE: The matrix metalloproteinases (MMPs) and their specific tissue inhibitors (TIMPs) have been implicated in tumor invasion and metastasis. Net matrix degradation and proteolysis depend on the critical local balance between MMPs/TIMP-2. We attempted to determine their expression balance and to evaluate its importance with tumor progression. METHODS: Expressions of MMP-2, MMP-9, and TIM P-2 mRNAs was quantified by reverse-transcription polymerase chain reaction (RT-PCR) in tumor tissues from 25 neuroblastoma patients. RESULTS: MMP-2, MMP-9, and TIMP-2 expression was observed in all the samples but with different trends. Increased expressions of MMP-2 mRNA was evident in advanced stages (Evans' stage III and IV; P = .02; unpaired ttest), and in patients who died of progressive disease (P = .0001). Whereas, the expressions of MMP-9 and TIMP-2 had no such significant association with clinical stages and prognosis. The ratio of MMP-2/TIMP-2 mRNAs was significantly higher in the advanced stages versus early stages (mean +/- SD = 1.66+/-0.65 and 1.11+/-0.34, respectively; P = .02) and in patients who died of progressive disease versus alive patients (mean = 2.13+/-0.78 and 1.21+/-0.36, respectively; P = .0006). CONCLUSIONS: Coexpression of MMPs and TIMP-2 in neuroblastoma indicates the need to evaluate their expression balance. Significantly higher expression of MMP-2 mRNA and increased ratio of MMP-2 and TIMP-2 mRNAs in advanced stages or patients who have died of progressive disease suggests an association between elevated MMP-2 expression and poor prognosis. To establish the role of enzyme to inhibitor mRNA ratio as a reliable predictor, cohort studies with significant number of cases may be carried out.

Immunohistochemical expression of MMP-2, MMP-9, and TIMP-2 in neuroblastoma: association with tumor progression and clinical outcome.

BACKGROUND/PURPOSE: The matrix metalloproteinases (MMPs) are responsible for degradation of the extracellular matrix. The MMPs and their specific tissue inhibitor metalloproteinases (TIMP) have been associated with tumor cell invasion and metastasis in a number of adult tumors. This study was carried out to detect their expression pattern in neuroblastoma and to evaluate whether they have any association with tumor progression and clinical outcome. METHODS: Cryostat sections of tumor tissues were collected from 31 patients with neuroblastoma, and immunohistochemical staining of MMP-2, MMP-9 and TIMP-2 with specific antibodies was performed according to labelled streptavidin-biotin method. RESULTS: MMP-2 and MMP-9 were coexpressed in neuroblastoma and exhibited an intratumor variability of staining intensity. MMP-2 and MMP-9 staining were confined mostly to the peritumoral stromal tissues rather than tumor cells and found positive in 80.6% cases and 71.0% cases, respectively. MMP-2 and MMP-9 immunoreactivity had no association with mass screened cases or with age of the patients. Increased expression of MMP-2 in stromal tissues of neuroblastoma had significant association with advanced clinical stages (chi2 test, P < .05). However, the expression of MMP-9 in neuroblastoma had no association with clinical stages and prognosis. However, TIMP-2 staining was confined mostly to the neoplastic cell cytoplasm, stromal tissue, and to the endothelial cells and accounted for 58.0% positivity. Decreased expression of TIMP-2 also had significant relationship with advanced clinical stages (chi2 test, P < .05). Kaplan-Meier survival curve showed that either increased expression of MMP-2 or decreased expression of TIMP-2 had relationship with poor clinical outcome. CONCLUSIONS: In neuroblastoma, stromal tissues are actively involved in the complex interaction between MMP-2 and TIMP-2 in extracellular matrix degradation during tumor progression, and TIMP-2 expression is inversely correlated with the corresponding MMP-2. An early detection of their expression pattern by immunohistochemistry in neuroblastoma may provide prognostic informations in clinical practice.

Histopathological variations among cases of Wilms' tumor in Bangladesh and its relationship with prognosis.

Recent advancement in the cytopathologic features produced a number of variants of Wilms' tumor which are the primary determinant of survival of Wilms' tumor patients. This study was carried out with 47 patients of Wilms' tumor in different stages in three selected hospitals from 1991 to 1993. Among them 61.7% (29) were in Favorable histopathology and 38.3% (18) were in Unfavorable histopathology group. After managing the patients with multimodal therapy according to the protocol of National Wilms' tumor Study-III the favorable group had shown better prognosis. The difference between two groups was statistically significant (chi-square = 3.2, P < 0.05). Histopathological variations could be easily determined which might improve the overall prognosis of Wilms' tumor.

Non-radioactive adenosine 5'-phosphosulfate sulfotransferase assay by coupling with sulfite reductase and O-acetylserine(thiol)lyase.

Adenosine 5'-phosphosulfate (APS) sulfotransferase is thought to be an enzyme that transfers the sulfo-group of APS to a carrier compound with a thiol group in the assimilatory sulfate reduction pathway of higher plants. We developed a rapid, non-radioactive assay for APS sulfotransferase. Sulfite released by APS sulfotransferase reaction in the presence of excess dithiothreitol was further converted to cysteine by coupling with yeast sulfite reductase and cabbage O-acetylserine(thiol)lyase. The cysteine thus formed was measured colorimetrically. By this method, 5 to 300 nmol of sulfite could be assessed. When the method was applied to APS sulfotransferase, the enzyme activity was APS-dependent with the partially purified enzyme. We could also detect APS sulfotransferase activity in some higher plants by this method.