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Objective This study aims to investigate the risk factors of prelaryngeal lymph node metastasis in papillary thyroid carcinoma and its clinical application value. Methods The clinical pathological features and metastatic risks were statistically analyzed by reviewing 254 patients with papillary thyroid carcinoma, who received their first operation and prelaryngeal lymph node dissection in our department. Results The detection of prelaryngeal lymph nodes, tumor size and any paratracheal lymph node metastasis were correlated with the number of paratracheal lymph node metastasis (P 0.05). Conclusion Paratracheal lymph node metastasis indicates a high possibility of prelaryngeal lymph node metastasis. Paratracheal lymph node dissection combined with prelaryngeal lymph node dissection should be simultaneously considered in operations for thyroid papilla carcinoma.

Purpose: This study was conducted to investigate the relation of HP infection to peripheral arterial stiffness and 10-year cardiovascular risk in diabetes mellitus (DM). Methods: DM subjects who underwent the C13-breath test were enrolled and divided into DMHP+ and DMHP− groups. Peripheral arterial stiffness was measured using brachial to ankle pulse wave velocity (baPWV). Framingham score (FRS) and Chinese evaluation method of ischemic cardiovascular diseases (ICVD) were used to clarify 10-year cardiovascular risk. Results: A total of 6767 subjects were included, baPWV and proportion of subjects with severe peripheral arterial stiffness were lower in DMHP− group than DMHP+ group (1556.68 ± 227.54 vs 2031.61 ± 525.48 cm/s, p

To observe the effect of catgut implantation at "Yingxiang"(LI20) on lower airway remodeling and levels of osteopon-tin (OPN) protein in allergic rhinitis (AR) rats, so as to reveal its mechanisms underlying improvement of AR.Male SD rats were randomly divided into control, model and catgut implantation groups, with 10 rats in each group. The AR model was established by intraperitoneal injection and nasal drip of ovalbumin. The catgut implantation was applied to bilateral "Yingxiang"(LI20) for 28 days in rats of the catgut implantation group. The total score of allergic symptoms of rats in each group were observed. The histopathological changes of lower airway were observed under light microscope after Hematoxylineosin, Periodic acid-Schiff and Masson staining. The expression of OPN protein was detected by immunohistochemistry and Western blot, separately.The total score of allergic symptoms of nose-wiping, running nose and sneezing, count of lung goblet cells, lung fiber content, and immunoactivity and expression levels of OPN protein were significantly increased in the model group in contrast to the control group (Acupoint implantation of catgut can improve pathological changes of lower airway remodeling, which may be related to its effect in down-regulating the expression of OPN protein in the lung tissue.

Objective This study aims to investigate the risk factors of prelaryngeal lymph node metastasis in papillary thyroid carcinoma and its clinical application value. Methods The clinical pathological features and metastatic risks were statistically analyzed by reviewing 254 patients with papillary thyroid carcinoma, who received their first operation and prelaryngeal lymph node dissection in our department. Results The detection of prelaryngeal lymph nodes, tumor size and any paratracheal lymph node metastasis were correlated with the number of paratracheal lymph node metastasis (P0.05). Conclusion Paratracheal lymph node metastasis indicates a high possibility of prelaryngeal lymph node metastasis. Paratracheal lymph node dissection combined with prelaryngeal lymph node dissection should be simultaneously considered in operations for thyroid papilla carcinoma.

Purpose: This study was conducted to investigate the relation of HP infection to peripheral arterial stiffness and 10-year cardiovascular risk in diabetes mellitus (DM). Methods: DM subjects who underwent the C13-breath test were enrolled and divided into DMHP+ and DMHP− groups. Peripheral arterial stiffness was measured using brachial to ankle pulse wave velocity (baPWV). Framingham score (FRS) and Chinese evaluation method of ischemic cardiovascular diseases (ICVD) were used to clarify 10-year cardiovascular risk. Results: A total of 6767 subjects were included, baPWV and proportion of subjects with severe peripheral arterial stiffness were lower in DMHP− group than DMHP+ group (1556.68 ± 227.54 vs 2031.61 ± 525.48 cm/s, p Conclusion: DM subjects with HP infection had more severe peripheral arterial stiffness compared those without HP infection, a higher cardiovascular risk score and 10-year cardiovascular risk stratification were observed in those subjects.

Elderly individuals with non-dipper hypertension are at high risk of cardiovascular disease because of increased stiffness of peripheral arteries. Since, vitamin D deficiency is prevalent in elderly Chinese. We examined whether reduced plasma levels of 25-hydroxyvitamin D [25(OH)D] may help promote this stiffness. Hypertensive patients at least 60 years old without history of peripheral arterial disease at our hospital were retrospectively divided into dipper and non-dipper groups according to the results of 24-hour ambulatory blood pressure monitoring. Plasma levels of 25(OH)D were measured by enzyme immunoassay. Peripheral arterial stiffness was measured based on the cardio-ankle vascular index (CAVI). Of the 155 patients enrolled, 95 (61.3%) were diagnosed with non-dipper hypertension and these patients had significantly lower plasma levels of 25(OH)D than the 60 patients with dipper hypertension (19.58 ± 5.97 vs 24.36 ± 6.95 nmol/L, P

Phytochromes in rice are encoded by a gene family composed of three members, PHYA, PHYB, and PHYC. Through characterizing the phytochrome mutants and wild type (WT) in terms of photomorphogenesis, roles of individual phytochromes have been preliminarily explored in regulating rice de-etiolation, flowering time and fertility. However, little information has been reported about whether or how phytochromes affect chlorophyll biosynthesis and chloroplast development in rice. In this study, we compared the chlorophyll contents of wild type and the phyA, phyB and phyAphyB mutants grown under either white light (WL) or red light (R). The results suggest that phyB perceives R to positively regulate chlorophyll biosynthesis, while the role of phyA can be detected only in the phyB-deficient mutant. Analyses of the expression levels of genes involved in chlorophyll biosynthesis revealed that phytochromes affected the chlorophyll biosynthesis by regulating protochlorophyll oxidoreductase A (PORA) expression. The role of phyB in chloroplast development was also analyzed, and the results suggest that phyB perceives R to regulate chloroplast development by affecting the numbers of chloroplasts and grana, as well as the chloroplast membrane system.

Due to factors such as objective conditions, time, and cost, it is impractical to carry out substantive indoor physical modeling experiments. Numerical simulation, whilst serving oilfield computation, is an economic technology with high speed and repeatability. Based on some typical physical modeling experiments, this paper establishes a numerical simulation model on laboratory units which complies with the experiments. This model aims at fitting displacement experimental dynamics and calibrating parameters in physical modeling experiments. Via this modeling and taking the experiment on profile controlling and flooding with weak gel as an example, computations over several schemes are accomplished, which visually reveal the mechanisms of fluid direction change, oil displacement, and injection profile improvement. The results demonstrate this approach a perfect combination of physical model experiment and numerical simulation, therefore can be widely used in a variety of displacement experiments for oilfield development, to achieve comprehensive studies while saving time and cost.

The incidence of breast cancer is increasing worldwide, and this seems to be related to an increase in lifestyle risk factors, including physical inactivity and overweight/obesity. We have reported previously that exercise induced a circulating angiostatic phenotype characterized by increased soluble fms-like tyrosine kinase-1 (sFlt-1) and endostatin and decreased unbound vascular endothelial growth factor (VEGF) in men. However, there are no data on women. The present study determines the following: (a) whether moderate exercise increased sFlt-1 and endostatin and decreased unbound VEGF in the circulation of adult female volunteers and (b) whether overweight/obese women have a higher plasma level of unbound VEGF than lean women. A total of 72 African American and White adult women volunteers ranging in age from 18 to 44 years were enrolled in the exercise study. All the participants walked on a treadmill for 30 min at a moderate intensity (55-59% heart rate reserve), and oxygen consumption (VO(2)) was quantified utilizing a metabolic cart. We obtained blood samples before and immediately after exercise from 63 participants. ELISA assays showed that the plasma levels of sFlt-1 were 67.8±3.7 pg/ml immediately after exercise (30 min), significantly higher than the basal levels, 54.5±3.3 pg/ml, before exercise (P

Several evidences revealed the interaction between phytochrome-mediated light signals and plant hormones abscisic acid (ABA) pathway in Arabidopsis . However, interaction between ABA signaling and phytochrome-mediated light signaling in mediating rice growth and development remain unclear. In the present study, we analyzed effects of PhyB -mediated light signals on ABA metabolism and ABA responses using rice wild type (WT) and the phyB mutant. It was observed that transcript levels of ABA biosynthetic genes (including OsNCED1 , OsNCED2 , OsNCED3 and OsNCED4 ) were higher in the phyB mutant than those in WT, whereas transcript level of ABA deactivating gene OsABA8OX1 was lower in the phyB mutant than that in WT, which probably contributed to the relatively high ABA content in the phyB mutant. ABA treatment inhibited germination of rice seeds grown either in the dark or under light. However, inhibitory effects of ABA treatment on seed germination were more obvious in phyB mutants relative to that in WT when seeds were grown under light conditions, suggesting that PhyB -mediated light signals attenuated the inhibitory effects triggered by ABA. Meantime, we compared the expression patterns of genes related to seed germination in WT and the phyB mutant grown in the medium with or without ABA. It was deduced that these genes is unlikely to contribute for the promotive effects of phyB-mediated light signals on seed germination. In addition, ABA treatment inhibited growth of both above-ground part and seminal root in rice seedlings. PhyB -mediated light signals did not affect the ABA-induced inhibition of above-ground part growth, but negatively regulate the inhibition of root growth. Taken together, our results suggest that PhyB -mediated light signals negatively regulate ABA accumulation and ABA responses in rice. This work reveals the influence of PhyB -mediated light signals on ABA pathway, which lays the foundation for dissecting the molecular mechanism of coordinated regulation of rice development by light and ABA in rice.

Based on the basic knowledge of ontology and protégé, and the deficiency of semantic expression in the IEC61850 and IEC61970 Standard, this paper puts forward a mapping method from SCL to CIM, adopting Web Ontology Language OWL to build the semantic information model of SCL and CIM of substation knowledge ontology. In substation model, this mapping method could solve the problem of information sharing and interoperation between digitized substation and dispatch master station, and lay a foundation for further research on fusion of the two standards.

There are lots of factors effect on weak gel flooding.This paper based on the conceptual model by changing the model parameters and using orthogonal design to analyze the effects of different factors on weak gel flooding. The descending order of influence is slug size, flooding time, oil-water viscosity ratio, permeability range, concentration of polymer, slug combination and polymer-cross linker ratio.

Phytochrome family mainly senses red and far-red light to regulate a range of developmental processes throughout the life cycle of plants. Rice phytochrome gene family is composed of three members known as PHYA, PHYB and PHYC. It has been elucidated that individual phytochromes display both unique and overlapping roles in rice photomorphogenesis by characterization of all rice phytochrome mutants including single mutants, all combinations of double mutants as well as triple mutants. Based on the published data and authors' ongoing studies, current knowledge of rice phytochrome functions in regulating seedling de-etiolation, root gravitropic response and elongation, plant architecture, flowering time and fertility is summarized. Additionally, the important issues in the field of rice phytochromes are proposed.

Obese postmenopausal women have a 50% higher risk of breast cancer than non-obese women. There is not an animal model that mimics postmenopausal obesity related to breast cancer progression. Using age-relevant C57BL/6 mice, this study determined whether postmenopausal obesity increases VEGF expression, tumor angiogenesis and breast tumor growth. Ovariectomy (OVX) was performed in 12 sixty week-old female mice, then followed by a low-fat (5%, LF, n = 6) or a high-fat (60%, HF, n = 6) diet for 12 weeks. In the eighth week of the dietary program, 106 E0771 (mouse breast cancer) cells were injected in the left fourth mammary gland. Tumor size was monitored for 4 weeks. Body weights were monitored weekly. At the end of the experiment, blood samples, visceral fat and tumors were collected for measuring VEGF expression using ELISA and intratumoral microvessel density (IMD) using CD31 immunochemistry. Body weight was significantly increased in OVX/HF mice, compared to OVX/LF group (55.3 ± 1.7 vs. 41.5 ± 1.5 g; p < 0.01). There was a two-fold increase in the ratio of visceral fat/BW in OVX/HF mice, compared to those in OVX/LF group (0.062 ± 0.005 vs. 0.032 ± 0.003; p < 0.01). Postmenopausal obesity significantly increased breast tumor weight over the control (4.62 ± 0.63 vs. 1.98 ± 0.27 g; p < 0.01) and IMD (173 ± 3.7 vs. 139 ± 4.3 IM#/mm2; p < 0.01). Tumor VEGF levels were higher in OVX/HF mice, compared to OVX/LF group (73.3 ± 3.8 vs. 49.5 ± 4.3 pg/mg protein; p < 0.01). Plasma VEGF levels (69 ± 7.1 vs. 48 ± 3.5 pg/ml) and visceral fat VEGF levels (424.4 ± 39.5 vs. 208.5 ± 22.4 pg/mg protein) were significantly increased in OVX/HF mice, compared to OVX/LF group, respectively (n = 6; p < 0.01). Interestingly, adipose tissue primary culture showed that subcutaneous fat released more VEGF, compared to visceral fat (6.77 ± 1.14 vs. 0.94 ± 0.16 pg/mg tissue; n = 6; p < 0.01). These findings support the hypothesis that postmenopausal obesity promotes tumor angiogenesis and breast cancer progression, possibly through increased adipose tissue mass and adipokines such as VEGF that could systemically and locally affect breast cancer progression.

Epidemiological studies suggest that obesity increases the risk of developing several cancers, including melanoma. Obesity increases the expression of angiogenic factors, such as leptin, that may contribute to tumor growth. However, a direct cause and effect relationship between obesity and tumor growth has not been clearly established and the role of leptin in accelerating tumor growth is unclear. Our objective in the present study was to examine the rate of melanoma tumor growth in lean and obese mice with leptin deficiency or high levels of plasma leptin. We injected 1 x 10(6) B16F10 melanoma cells subcutaneously into lean wild type (WT), obese melanocortin receptor 4 knockout (MC4R(-/-)), which have high leptin levels, obese leptin-deficient (ob(-/-)), pair fed lean ob(-/-), and lean ob(+/-) mice. Mean body weights were 29.7 +/- 0.3 g (WT), 46.3 +/- 1.9 g (MC4R(-/-)), 63.7 +/- 0.9 g (ob(-/-)), 30.5 +/- 1.0 g (pair fed ob(-/-)) and 31.6 +/- 1.7 g (ob(+/-)). Tumors were much larger in the obese leptin deficient ob(-/-) (5.1 +/- 0.9 g) and obese MC4R(-/-) (5.1 +/- 0.7 g) than in lean WT (1.9 +/- 0.3 g) and ob(+/-) (2.8 +/- 0.7 g) mice. Prevention of obesity by pair feeding ob(-/-) mice dramatically reduced tumor weight (0.95 +/- 0.2 g) to a level that was significantly lower than in WT mice of the same weight. Tumor VEGF levels were the highest in the obese mouse tumors (p0.05), regardless of the host leptin levels. Except for the lean ob(+/-), MC4R(-/-) and ob(-/-) melanomas had the highest VEGF receptor 1 and VEGF receptor 2 protein expression (p0.01 and p0.05), respectively. These results indicate that obesity markedly increases melanoma tumor growth rate by mechanisms that may involve upregulation of VEGF pathways. Although tumor growth does not require host leptin, melanoma tumor growth may be accelerated by leptin.

Clinical evidence links the inhibition of VEGF to hypertension. However, the mechanisms by which VEGF affects the pathogenesis of hypertension remain in question. We determined 1) whether administration of VEGF receptor inhibitor SU5416 enhances dietary salt-induced hypertension in Sprague-Dawley (SD) rats, and 2) whether VEGF or SU5416 directly affects proliferation of cultured human renal proximal tubular epithelial cells (HRPTEC) and endothelial nitric oxide synthase (eNOS) expression in cultured human glomerular microvessel endothelial cells (HGMEC). Ten 10-wk-old male SD rats received a high sodium diet (HS; 8%) and the other 10 SD rats received a normal sodium diet (NS; 0.5%) for 4 wks. After 2 wks of the dietary program, five rats were administered with SU5416 at 10 mg·kg−1·day−1ip or DMSO (vehicle) for 14 days in HS and NS groups. Mean arterial pressure was significantly higher in rats treated with SU5416, as opposed to those treated with DMSO and fed with HS for 4 wk (157.6 ± 3.9 vs. 125.9 ± 4.3 mmHg, P < 0.01). Increased proteinuria and albuminuria were associated with marked renal histological abnormalities in HS group with SU5416 administration, compared with those in the vehicle HS group. 3H-thymidine incorporation assay showed that SU5416 blocked the actions of both exogenous and endogenous VEGF on the proliferation of HRPTEC. VEGF (10 ng/ml) significantly increased eNOS protein levels by 29% in cultured HGMEC, but its action was completely abolished by SU5416. These results suggest that VEGF receptor inhibition enhances dietary salt-induced hypertension and kidney injury, possibly by direct damage on renal cells and decreasing NO production by eNOS.

The role of angiostatic factors, including endostatin, in regulating physiological angiogenesis is poorly understood. We used normal adult rats under physiological resting conditions to examine the relationship between tissue endostatin, VEGF, and capillary density (CD) in the heart (high metabolic activity) versus the skeletal muscle (relatively low metabolic activity). The heart (left ventricle, LV) and skeletal muscle (anterior tibialis, AT) were dissected from 12-week-old male Sprague-Dawley rats. Transverse cryosections of LV and AT were stained with FITC-conjugated GS-I-lectin. CD was determined by analysis of randomly acquired digital images of the cryosections using Optimas software. Tissue protein levels of endostatin and VEGF were determined by ELISA assays. Tissue endostatin levels were lower in the LV and higher in the AT (135 +/- 39 vs. 663 +/- 114 pg/mg) and VEGF levels were higher in the LV and lower in the AT (41 +/- 3 vs. 27 +/- 4 pg/mg), respectively (n = 7, P < 0.01). CD in LV and AT were 3632 +/- 428 and 437 +/- 44/mm2, respectively (P < 0.01). We demonstrated that an 8.3-fold greater capillary density is related to a 4.9-fold lower level of tissue endostatin and a 1.5-fold higher level of tissue VEGF in the heart (LV) versus the skeletal muscle (AT) of normal rats under physiological resting conditions. Also, exercise training increased capillary density, decreased tissue endostatin and increased tissue VEGF in the skeletal muscle (AT). These findings suggest that tissue endostatin content correlates inversely with capillary network in the muscle tissues with different metabolic activity, and that tissue endostatin may play a very important role in the metabolic control of angiogenesis under physiological conditions.

Melanoma is a highly malignant cancer with a potent capacity to metastasize distantly and has a higher mortality. There is no effective therapy for high risk melanoma patients to prevent relapse or distant metastasis. Therefore effective chemoprevention strategies are needed. The present study mainly evaluates the effects of EGCG on melanoma angiogenesis, growth, and capillary density (CD) in the heart and skeletal muscles of mice. 5 x 10^5 B16F10 cells were inoculated into the right proximal dorsal of the back in the eight week old male mice (n=12). Then, 6 mice received EGCG at 50-100 mg/kg/d in drinking water for 4 weeks and 6 control mice received drinking water only. Tumor size was monitored using dial calipers. At the end of the experiment, blood samples, tumors, hearts, and limb muscles were collected and measured for VEGF expression using ELISA and capillary density (CD) using CD31 immunohistochemistry. Compared to the control, EGCG treatment significantly reduced tumor weight (2.9±0.5 vs. 5.9±1.1 g; P

Abstract —The mechanisms of sodium-induced myocardial hypertrophy and vascular hypertrophy are poorly understood. We tested the hypothesis that a high sodium concentration can directly induce cellular hypertrophy. Neonatal rat myocardial myoblasts (MMbs) and vascular smooth muscle cells (VSMCs) were cultured in a 50:50 mixture of DMEM and M199 supplemented with 10% fetal bovine serum. When the monolayers reached ≈80% confluence, normal sodium medium (146 mmol/L) was replaced with high sodium media (152 mmol/L, 160 mmol/L, and 182 mmol/L) for up to 5 days. Increasing sodium from a baseline concentration of 146 mmol/L to the higher concentrations for 5 days caused dose-related increases in cell mean diameter, cell volume, and cellular protein content in both MMbs and VSMCs. Increasing the sodium concentration by only 4% (from 146 mmol/L to 152 mmol/L) caused the following respective changes in MMbs and VSMCs: 8.5% and 8.7% increase in cell mean diameter, 27.6% and 27.0% increase in cell volume, and 55.7% and 46.7% increase in cellular protein content. The rate of protein synthesis, expressed as [ 3 H]leucine incorporation, increased by 87% and 99% in MMbs after exposure to 152 mmol/L and 160 mmol/L sodium, respectively, compared with the 146-mmol/L sodium control group. Exposure of MMbs to medium with a sodium concentration of 10% above normal, ie, 160 mmol/L, caused a significant decrease (range, 26% to 44%) in the rate of protein degradation at multiple time points over a 48-hour period compared with normal sodium control cells. The increase in cellular protein content caused by 160 mmol/L sodium returned to normal within 3 days after MMbs were returned to a normal sodium medium. These findings support the hypothesis that sodium has a direct effect to induce cellular hypertrophy and may therefore be an important determinant in causing myocardial and/or vascular hypertrophy in subjects with increased sodium concentration in the extracellular fluid.

Background Basic fibroblast growth factor (bFGF) is a mitogenic polypeptide that demonstrates enhanced expression and promotes angiogenesis in animal models of myocardial ischemia and infarction. Elevated levels of bFGF are present in the urine of humans with metastatic tumors, but its expression in human myocardial ischemia is unknown. Thus, we sought to determine whether urine levels of bFGF are altered by exercise-induced ischemia in humans. Methods and Results Eighty-six patients underwent exercise thallium studies for evaluation of anginal symptoms. Urine levels of bFGF (corrected for urine creatinine) were determined by ELISA immediately before and between 2 and 4 hours after exercise. The change in urine bFGF level was compared between 43 patients with and 43 patients without exercise-induced ischemia. Patients with ischemia had an increase in urine bFGF compared with nonischemic patients (1052±245 versus −278±130 pg/g creatinine, P P P P Conclusions Significantly increased levels of bFGF are detected in the urine within hours of exercise-induced ischemia. Further studies are warranted to determine whether bFGF might serve as a useful circulating marker of myocardial ischemia in humans.

We previously reported that postmenopausal obesity is associated with increased angiogenesis in adipose tissue. The Present study determines whether Sunitinib is effective in treating postmenopausa...

The role of EGCG, a major green tea catechin in breast cancer therapy is poorly understood. The present study tests the hypothesis that EGCG can inhibit the activation of HIF-1α and NFκB, and VEGF expression, thereby suppressing tumor angiogenesis and breast cancer progression. Sixteen eight-wk-old female mice (C57BL/6 J) were inoculated with 10^6 E0771 (mouse breast cancer) cells in the left fourth mammary gland fat pad. Eight mice received EGCG at 50–100 mg/kg/d in drinking water for 4 weeks. 8 control mice received drinking water only. Tumor size was monitored using dial calipers. At the end of the experiment, blood samples, tumors, heart and limb muscles were collected for measuring VEGF expression using ELISA and capillary density (CD) using CD31 immunohistochemistry. EGCG treatment significantly reduced tumor weight over the control (0.37 ± 0.15 vs. 1.16 ± 0.30 g; P

SU11248 is a selective inhibitor of certain protein kinases including VEGFR types 1–3 that are expressed in human breast cancer. The present study determines whether the anti-tumor activity of SU11248 results from the inhibition of angiogenesis, as well as direct anti-proliferation and anti-migration effects on breast tumors. Eight-wk old female mice (C57BL/6) were given SU11248 at 20–40 mg/kg/d in drinking (distilled) water for 4 wks. Control mice received drinking water only. In the 2nd wk, 106 E0771 (mouse breast cancer) cells were injected in the left fourth mammary gland. Tumor size was monitored using dial calipers. At the end, tumors were isolated for measuring tumor size and intratumoral microvessel density (IMD) using CD31 immunohistochemistry. SU11248 significantly reduced tumor weight over the control (1.22 ± 0.28 vs. 3.28 ± 0.31 g; n = 8; p < 0.01) and IMD (111 ± 10 vs. 155 ± 6 IM#/mm2; p < 0.01). RT-PCR indicated that VEGFR1 and R2 were expressed in cultured E0771 cells. VEGF (10 ng/ml) caused a 42% increase in proliferation of E0771 cells, compared to the control (p < 0.01; n = 8), and there was a significant decrease in proliferation of E0771 cells treated with VEGF plus SU11248 (10 µmol/L) vs. the control (65%, p < 0.01). VEGF caused a 2-fold increase in the proliferation of HUVEC vs. the control (p < 0.01; n = 8), but its action was completely eradicated by SU11248. Neither VEGF nor SU11248 had any effect on the proliferation of cultured HAS MC. Migration assay showed that SU11248 (10 µmol/L) significantly inhibited the migration of cultured E0771 cells. SU11248 significantly inhibited the proliferation of MCF-7 and MDA-MB-231 cells in a dose-related manner. These findings support the hypothesis that the anti-tumor activity of SU11248 on breast cancer is possibly mediated by targeting the paracrine and autocrine effects of VEGF on breast cancer to suppress tumor angiogenesis, proliferation and migration.

CP-74,667, a 6-fluoro-7-bridged piperazinyl-1-cyclopropyl-4 quinolone, inhibited 90% of staphylococci, β-hemolytic streptococci, enterococci, Enterobacteriaceae, and Pseudomonas aeruginosa at ≤ 2 μ g/ml. Ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus had minimum inhibitory concentration (MIC 50 ) of 4 μg/ml and an MIC 90 of 8 μg/ml. CP-74,667 was fourfold more active than ciprofloxacin against Streptococcus pneumoniae and St. pyogenes , but equal or less active than tosufloxacin against Gram-positive species. The MIC 90 for P. aeruginosa was 5 μg/ml similar to temafloxacin. The CP-74,667 MIC 90 for Bacteroides fragilis was 2 μg/ml, equal to tosufloxacin and temafloxacin. Activity was eight- to 16-fold less at pH 5.5 compared with pH 7.4 and also eight- to 16-fold less in urine. Magnesium ions markedly increased the CP-74,667 minimum bactericidal concentrations (MBCs). The development of resistance to CP-74,667 was similar to that found for other fluoroquinolones.

The in vitro activity of cefquinome, a new aminothiazolyl cephalosporin with a C-3 bicyclic pyridinium group, was compared with ceftazidime, cefpirome, and cefepime. Cefquinome inhibited members of the Enterobacteriaceae at less than or equal to 0.5 microgram/ml for Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Citrobacter diversus, Salmonella Shigella, Proteus mirabilis, Morganella, and Providencia. Although most Citrobacter freundii and Enterobacter cloacae were inhibited by less than 2 micrograms/ml, some strains resistant to ceftazidime were resistant, [minimum inhibitory concentration (MIC) greater than 16 micrograms/ml]. Serratia marcescens were inhibited by less than 1 microgram/ml and Pseudomonas aeruginosa by 8 micrograms/ml similar to the activity of cefepime. The majority of Haemophilus influenzae and Neisseria gonorrhoeae were inhibited by less than 0.25 microgram/ml. Most enterococci had cefquinome MICs of 4-8 micrograms/ml. Cefquinome was extremely active against group-A streptococci and Streptococcus pneumoniae with MICs less than 0.12 microgram/ml. 90% of methicillin-susceptible Staphylococcus aureus 90% were inhibited by 2 micrograms/ml. Overall, the in vitro activity of cefquinome was comparable with aminothiazolyl cephalosporins. It inhibited some Enterobacter and Citrobacter freundii resistant to ceftazidime as did cefpirome and cefepime. Cefquinome was not destroyed by the common plasmid beta-lactamases TEM-1, TEM-2, SHV-1, or by the chromosomal beta-lactamases of Klebsiella, Branhamella, and Pseudomonas, but it was hydrolyzed by TEM-3, TEM-5, and TEM-9. Its activity was not adversely decreased in different medium or protein, and minimum bactericidal concentrations (MBCs) for most species except for Enterobacter were within a dilution of MICs.

The present study examines whether a long-term high salt diet causes hypertension and renal injury in normal subjects [Sprague-Dawley (SD) rats] and alters renal cytokine-related gene expression profiles.Four 10 week old male SD rats received a high salt diet (HS, 8%) and the other 4 SD rats received a normal salt diet (NS, 0.5%) for 8 weeks. Mean arterial pressure (MAP) and renal damages such as albuminuria and histological renal injury were determined. The relative mRNA levels of 514 cytokine-related genes (normalized by beta-actin) in rat kidneys following NS or HS were determined quantitatively through analysis of 4 sets of gene expression profiles using the mouse cDNA membrane microarrays.We demonstrated that 8 weeks of HS diet increased MAP [(140.0+/-5.3) vs (112.0+/-2.2) mmHg; 1 mmHg=0.133 kPa, P0.01], albuminuria [(41.4+/-3.2) vs (20.1+/-4.5) mg/d; P0.01], and caused histological renal injury in SD rats, compared to NS group. Of the 514 genes in the array, there were 27 (5.25%) genes with significantly different expression in the kidney of SD rats with HS compared to those of SD rats with NS. Functional clustering analysis indicated the following functional pathways related to high salt diet-induced hypertension: (1) pro-inflammatory response ( upward arrowIL-17, CCL28; downward arrow NFkappabib); (2) endothelial dysfunction ( downward arrowVEGF-A, VEGF-B, endoglin); (3) pro-matrix formation ( upward arrowosteopontin, IGFBP-5; downward arrow IFN-gamma); and (4) attenuated cell survival and differentiation ( downward arrowCNTF, IGF-II R, ephrin-B1). Northern blot confirmed that 8 weeks of HS diet significantly decreased renal expression of VEGF mRNA, compared to NS group (P0.01). ELISA showed that HS diet significantly decreased renal protein levels of VEGF and CCL28.These findings support the hypothesis that hypertension can be induced in normal rats by a long-term high salt diet, which is associated with increased renal injury and marked changes in renal cytokine gene expression profiles that are closely related to the pro-inflammatory response, pro-matrix formation, endothelial dysfunction, and attenuated cell survival and differentiation.

The progression of breast cancer is associated with oxidative stress. However, the effects of pyrrolidine dithiocarbamate (PDTC), a known antioxidant, on the development of breast cancer are poorly understood. The present study evaluates the effects of PDTC on tumor growth, the expression of vascular endothelial growth factor (VEGF), and angiogenesis of breast cancer in female mice. Eight week old female mice (C57BL/6J) were given PDTC at 100 to 200 mg/kg/day for 3 weeks (n=10). The control mice received regular drinking water only. In the 2nd wk, 5x10^5 E0771 (mouse breast cancer) cells were injected in the pad of the fourth mammary gland of the mice. Tumor size was monitored using dial calipers. At the end of the experiment, the tumors were isolated and measured for tumor size, intratumoral microvessel (IM) density using CD31 immunohistochemistry staining, NFκB activation using EMSA, and VEGF protein levels using ELISA. PDTC treatment caused a significant decrease in tumor weight compared to the control (0.64±0.22 vs. 1.43±0.31 g; n=8; P0.01), and a significant decrease in IM density (66.1±5.3 vs. 84.2±9.4 IM# /mm^2; P0.01). There was a significant decrease in tissue protein levels of VEGF (22.6±2.1 vs. 32.4±2.6 pg/mg) and a 43% reduction NFκB activation in the breast tumors of mice treated with PDTC compared to the control group (P0.01). Western blot indicated that estrogen receptor-α (ERα), VEGF receptor-1 (Flt-1), and VEGF receptor-2 (Flk-1) were expressed in E0771 cells. VEGF receptor inhibitor SU5416 and PDTC synergistically suppressed the proliferation of E0771 cells. PDTC also significantly inhibited the migration of cultured E0771 cells. These results support the hypothesis that PDTC suppresses tumor angiogenesis, growth, and migration of breast cancer via inhibiting autocrine and paracrine effects of VEGF through the reduction of NFκB activation and VEGF expression.

We seek to determine: 1) whether a long-term high salt diet induces hypertension and renal injury in Sprague-Dawley (SD) rats and 2) whether the high salt diet-induced hypertension and renal injury are associated with decreased renal VEGF expression. Twelve 10-wk-old male SD rats received a high salt diet (HS, 8%) and twelve SD rats received a normal salt diet (NS, 0.5 %) for 8 weeks. Using a tail cuff, weekly monitoring showed that blood pressure increased significantly after 6, 7, & 8 wks in HS group, compared to NS group (P

The serum bactericidal activity of clarithromycin in six normal human volunteers was determined after oral doses of 500 mg. The mean plasma levels of clarithromycin plus 14-hydroxy clarithromycin were 2.11 micrograms/mL after the second dose and 4.36 micrograms/mL after the sixth dose. The mean serum bactericidal titer against Haemophilus influenzae after the second dose was 1:8 and after the sixth dose 1:16 when unheated serum was used. Similar values were obtained when serum to which clarithromycin and 14-hydroxy clarithromycin was added was tested. Mean serum bactericidal titers against H. influenzae determined in Haemophilus test broth or heated serum were 1:2 and 1:4, respectively. Against Streptococcus pneumoniae and Streptococcus pyogenes, there was greater than 1:16 serum bactericidal levels at 12 hours after the sixth dose of clarithromycin.

OCP 9-176 is an oxycephem antibiotic that contains a 2-aminothiazolyl, carboxypropyl side chain at C-7 and a pyridinium thiomethyl group at C-3. OCP 9-176 was generally twofold less active than its sulfur-containing analog ME 1228 against Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Providencia stuartii, Proteus vulgaris, and Serratia marcescens. Activity against Enterobacter cloacae and Citrobacter freundii was equivalent. OCP 9-176 was twofold less active than ME-1228 against Pseudomonas aeruginosa and Acinetobacter species. Activity of the two agents was similar against Staphylococcus aureus and Staphylococcus epidermidis. Although OCP 9-176 inhibited E. coli containing TEM-1 and TEM-2, it was less active than ME-1228. Klebsiella organisms with SHV-1 and K-2 beta-lactamases were inhibited, but TEM-3-containing isolates had MICs of 16 micrograms/ml. OCP 9-176 was minimally hydrolyzed by TEM-1, PSE-1, K-1, and P99, and it was a poor inhibitor of P99. Replacement of sulfur with oxygen does not increase the activity of compounds with sulfopyridinium methyl groups at C-3.

Sparfloxacin, a new fluoroquinolone, inhibited the majority of members of the family Enterobacteriaceae at less than or equal to 1 microgram/ml. It was less active than ciprofloxacin but more active than ofloxacin. Against Pseudomonas aeruginosa, it was less active than ciprofloxacin but twofold more active than ofloxacin. It inhibited Staphylococcus aureus and most Streptococcus pneumoniae and Streptococcus pyogenes isolates at 0.25 micrograms/ml, whereas ciprofloxacin and ofloxacin inhibited these isolates at 2 micrograms/ml. Bacteroides fragilis was inhibited by less than or equal to 2 micrograms/ml. Sparfloxacin was less active at an acidic pH and in the presence of Mg2+. Resistance to sparfloxacin was produced by repeated exposure, although the frequency of single-step mutants was less than 10(-9).

GR69153, a new parenteral cephalosporin, inhibited 90% of Escherichia coli, Klebsiella oxytoca, Proteus mirabilis, Citrobacter diversus, shigellae, and salmonellae at less than 0.25 micrograms/ml (MIC90). It had activity comparable to those of ceftazidime, cefpirome, cefepime, and E-1040. Against cephalosporinase-producing Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens, MICs ranged from 0.12 to greater than 32 micrograms/ml, and cefpirome and cefepime were the most active agents against these species. Pseudomonas aeruginosa was highly susceptible to GR69153, and for this organism the MIC90 was less than or equal to 2 micrograms/ml, which was similar to the E-1040 MIC90, but most Pseudomonas cepacia and Xanthomonas maltophilia isolates were resistant. GR69153 inhibited Haemophilus influenzae and Moraxella branhamella at less than or equal to 0.5 micrograms/ml. For Staphylococcus aureus GR69153 MICs were similar to those of ceftazidime and E-1040. Enterococci and listeriae were resistant to GR69153, but Streptococcus pyogenes and Streptococcus pneumoniae were inhibited by 0.5 micrograms/ml. The activity of GR69153 was not affected by serum. GR69153 was not inactivated by the beta-lactamases of Staphylococcus aureus, TEM-1, TEM-2, SHV-1, and BRO-1, but it was hydrolyzed by TEM-3, TEM-9, and morganellae. GR69153 had overall activity comparable to those of commercially available parenteral cephalosporins or those found in clinical investigations. It is more active against bacteroides than most available aminothiazolyl parenteral cephalosporins are. GR69153 is hydrolyzed by the new plasmid beta-lactamases, and thus, its primary value may be related to its pharmacological properties.

Ceftibuten is a new beta-lactamase-stable 3-aminothiazolyl cephalosporin that lacks activity against staphylococci and group-B streptococci. We determined the effect of the combination of ceftibuten with SCH 29482, an orally absorbed penem. The combination of the two agents was additive for 25% or indifferent for 57% of the Gram-positive species, Haemophilus, and Moraxella tested with a mean fractional inhibitory concentration (FIC) index of 0.75. The combination of ceftibuten and SCH 29482 was also indifferent for Bacteroides fragilis and other Bacteroides species, all of which were inhibited by less than or equal to micrograms/ml of SCH 29482. Antagonism of the combination was found for 80% of Serratia marcescens and for 30% of Citrobacter freundii and Enterobacter cloacae. Overall, the combination of ceftibuten and SCH 29482 at concentrations that can be achieved in serum after ingestion of 400 and 50 micrograms/ml, respectively, provided antibacterial activity against most Gram-positive aerobic and anaerobic species that cause upper respiratory, intraabdominal, and urinary infections.

Recent studies show that certain tyrosine kinase inhibitors target both tumor vasculature and tumor cell. We determine whether the mouse breast cancer cells (E0771) express VEGF receptor-1 and 2, a...

The mechanisms of alcohol-induced cancer in humans are unclear. We used the immunocompetent mice implanted with B16F10 cells to evaluate the effects of physiologically relevant EtOH intake on tumor growth and angiogenesis of melanoma. Six-wk-old male mice (C57BL/6J) were given 1% EtOH in drinking water for 12-hrs during the night which was then replaced with regular water during the remaining 12-hrs each day for 4 wks (n = 10). The control mice received regular drinking water only. In the second week, all mice were inoculated subcutaneously on the right proximal dorsal with 5 x 10(5) B16F10 cells. In the end, the tumors were isolated for measuring tumor size, average microvascular density (AMVD) using CD31 immunohistochemistry, and the expression of VEGF and its receptor (Flt-1) using Northern blot, ELISA, and immunohistochemistry. EtOH intake caused a 2.16-fold increase in tumor weight over the control (4.81 +/- 0.39 vs. 2.23 +/- 0.48 g; n = 10; p = 0.003), a 2.02-fold increase in AMVD (60.63 +/- 5.56 vs. 30.01 +/- 7.41/mm(2); p = 0.0014), and a significant increase in VEGF mRNA and protein expression plus Flt-1 protein levels in melanoma compared to the control group (p < 0.01). These results suggest that progression of melanoma growth and angiogenesis may be mediated by upregulation of VEGF and Flt-1, especially under the influence of EtOH.