Effect of siRNA targeting HER2/neu on the proliferation and viability of prostate cancer PC-3M cells.

The aim of this study was to investigate the effect of a small interfering RNA (siRNA) targeting human epidermal growth factor receptor 2 (HER2/neu) on the proliferation and viability of prostate cancer PC-3M cells. Chemically synthesized siRNA targeting HER2/neu was transfected into PC-3M cells by using liposomes, and cells transfected with empty liposomes, a negative siRNA sequence, or nothing (untransfected) were used as controls. mRNA and protein levels of HER2/neu were detected using reverse transcription-polymerase chain reaction and western blot, respectively. The inhibitory action of HER2/neu siRNA on the in vitro growth of PC-3M cells was assessed by the cholecystokinin 8 assay and apoptosis was detected using flow cytometry. Cells transfected with HER2/neu siRNA showed decreased mRNA and protein levels of HER2/neu compared to control groups (P < 0.05). The survival rate of PC-3M cells decreased significantly after transfection with HER2/neu siRNA compared to that of untransfected cells (55.39 ± 1.60 and 81.42 ± 0.80%, respectively; P < 0.05). The apoptosis rate in cells transfected with HER2/neu siRNA was quite high (45.60 ± 0.70%) compared to that of blank control, empty liposome, and negative siRNA sequence groups (P < 0.05). In conclusion, siRNA targeting HER2/neu inhibits HER2/neu expression in PC-3M cells, resulting in an inhibition in proliferation and an induction of apoptosis.

Untangle the Structural and Random Zeros in Statistical Modelings.

Count data with structural zeros are common in public health applications. There are considerable researches focusing on zero-inflated models such as zero-inflated Poisson (ZIP) and zero-inflated Negative Binomial (ZINB) models for such zero-inflated count data when used as response variable. However, when such variables are used as predictors, the difference between structural and random zeros is often ignored and may result in biased estimates. One remedy is to include an indicator of the structural zero in the model as a predictor if observed. However, structural zeros are often not observed in practice, in which case no statistical method is available to address the bias issue. This paper is aimed to fill this methodological gap by developing parametric methods to model zero-inflated count data when used as predictors based on the maximum likelihood approach. The response variable can be any type of data including continuous, binary, count or even zero-inflated count responses. Simulation studies are performed to assess the numerical performance of this new approach when sample size is small to moderate. A real data example is also used to demonstrate the application of this method.

Mechanisms responsible for sustained hypotension after captopril treatment.

OBJECTIVE: To investigate new aspects of the relationship between sustained reduction of blood pressure and alteration of cardiovascular structure and function after cessation of early captopril treatment. METHODS: Spontaneously hypertensive rats (SHR) were given captopril 20 mg/kg per day (n = 13) or 100 mg/kg per day (n = 12) from the intra-uterine period to age 16 weeks and then the treatment was stopped. Age-matched untreated SHR (n = 16) and Wistar-Kyoto (WKY) rats (n = 17) served as controls. The experiments were carried out at 40 weeks. RESULTS: Withdrawal of captopril treatment resulted in a rapid rebound of SBP to a level close to that of untreated SHR in the low-dose group, whereas a persistently lower SBP was maintained in the high-dose group. Both doses of captopril treatment completely prevented wall hypertrophy either of arteriolar resistance vessels or of muscular vessels. Captopril decreased left ventricular mass:body weight ratio dose-dependently. High-dose captopril improved the resting and stress systolic and diastolic function. Thoracic angiotensin converting enzyme levels were dose-dependently reduced by captopril treatment. The curves of perfusion pressure response to incremental doses of phenylephrine shifted to the right in both captopril treatment groups compared with those of the control SHR. Addition of L-NAME and L-arginine to the perfusate augmented or attenuated the vasoconstrictor activity in all of the rats, whereas high-dose captopril totally restored the abnormal hypersensitivity to L-NAME and caused less attenuation in response to L-arginine in the control SHR. CONCLUSIONS: The persistent lower blood pressure caused by early captopril treatment was ascribed mainly to its sustained normalization of structure and function of resistance vessels, which may be partly mediated by the improvement of endothelial cell function. The persistent reduction of angiotensin converting enzyme activity in blood vessel wall attenuated left ventricular hypertrophy, and the improvement of cardiac systolic and diastolic function may also contribute to the sustained hypotensive effect.

A nonlinear isobologram model with Box-Cox transformation to both sides for chemical mixtures.

The linear logistical isobologram is a commonly used and powerful graphical and statistical tool for analyzing the combined effects of simple chemical mixtures. In this paper a nonlinear isobologram model is proposed to analyze the joint action of chemical mixtures for quantitative dose-response relationships. This nonlinear isobologram model incorporates two additional new parameters, Ymin and Ymax, to facilitate analysis of response data that are not constrained between 0 and 1, where parameters Ymin and Ymax represent the minimal and the maximal observed toxic response. This nonlinear isobologram model for binary mixtures can be expressed as [formula: see text] In addition, a Box-Cox transformation to both sides is introduced to improve the goodness of fit and to provide a more robust model for achieving homogeneity and normality of the residuals. Finally, a confidence band is proposed for selected isobols, e.g., the median effective dose, to facilitate graphical and statistical analysis of the isobologram. The versatility of this approach is demonstrated using published data describing the toxicity of the binary mixtures of citrinin and ochratoxin as well as a new experimental data from our laboratory for mixtures of mercury and cadmium.

Nifedipine pharmacodynamics and pharmacokinetics in treatment of congestive heart failure.

In 22 of 27 cases of congestive heart failure (CHF) treated with nifedipine (NIF), significant improvements in resting hemodynamics were noticed. The higher the basal systemic vascular resistance (SVR) and pulmonary artery end diastolic pressure (PAEDP), the greater the magnitude of reduction was achieved (r = 0.84 and 0.77, P less than 0.01, respectively). Exercise hemodynamic investigation showed that NIF lowered SVR, PAEDP and pulmonary vascular resistance (PVR), with an increase in stroke volume (SV) at the serum concentration of 5-10 ng/ml. Maximum effect was observed at the concentration of 20 ng/ml. No further vasodilation was attainable with serum concentrations above 20 ng/ml. No remarkable deviation of NIF pharmacokinetic parameters from the normal ranges was found in CHF patients. The plasma norepinephrine level decreased markedly 2 and 7 hours after the use of NIF. It is concluded that oral NIF is beneficial to severe CHF patients with low cardiac output and high SVR.

Interactive toxicity of simple chemical mixtures of cadmium, mercury, methylmercury and trimethyltin: model-dependent responses.

Scientific and societal interest in the analysis of aggregate toxicity derives from the fact that people are seldom exposed to single chemicals, but rather to multiple agents from different sources and even to mixtures of agents from a single source. Many descriptive terms and mathematical, graphical, and statistical models have been used to evaluate the toxicity of simple mixtures. It is not very easy to distinguish clearly the intrinsic differences, distinctions and limitations of these models when applied to characterizing interactive toxicity. A series of experiments were performed to illustrate model-dependent consistencies and differences in interactive toxicity. Cultured murine renal cortical cells, target cells for metal toxicity, were treated with selected concentrations of one metal or binary mixtures of metals to give conditions of dose-additivity, response additivity, or with only one toxic member of the binary mixture. The cytotoxicity was determined at 24h by lactate dehydrogenase release. The data were analyzed graphically and mathematically by (a) Carter's statistical isobologram, (b) Barton's non-linear, and (c) Kodell and Pounds' linear models to characterize the interaction. These models were compared and contrasted for robustness, and consistency using these common data sets. The models gave generally consistent conclusions, but each model has limitations and strengths for assessing particular mixtures scenarios. This comparison illustrates the complexity of extrapolating conclusions between models, and difficulty of public health assessment from exposures to multiple chemicals in the environment.

[Mechanism of inhibition in left ventricular hypertrophy by captopril treatment in spontaneously hypertensive rats].

To explore the mechanisms by which angiotensin converting enzyme inhibitor (ACEI) prevents the development of left ventricular hypertrophy (LVH), captopril (Cap 100 mg.kg-1/d was administered orally to male spontaneously hypertensive rats from intrauterine period to 16 weeks of age. Male and age-matched untreated WKY rats and SHR were used as controls. Experiments were performed at 40 weeks of age. SBP, left ventricular weight to body weight ratio (LVW/BW), myocardial hydroxyproline (Hypro) and norepinephrine (NE) were determined. The levels of c-myc and c-fos mRNA in the left ventricle were measured by Northern blot. Early-onset Cap therapy significantly decreased SBP at 16 weeks of age. After discontinuance of treatment for 24 weeks, SBP of SHRcap was still maintained at a level lower than that of untreated SHR. LVW/BW and Hypro in SHR cap were markedly reduced. The expression of myocardial c-myc mRNA (n = 5) was decreased by 72% in SHRcap compared with that in the untreated SHR, but the expression of c-fos mRNA (n = 7) and NE was not different between the untreated SHR, SHRcap and WKY rats. These results indicate that early Cap treatment may permanently prevent the development of hypertension, inhibit myocardial hypertrophy (MH), and interstitial fibrosis. Furthermore, the prevention of MH is associated with a decrease in myocardial c-myc mRNA levels, and the development and regression of MH may be irrelevant to proto-oncogene c-fos expression.

[Study of helical CT low-contrast resolution and its influencing factors].

This paper studies the helical CT low-contrast resolution and its influencing factors by experimental analysis. The CT low-contrast resolution increased with mA, kV, slice thickness, scan time and FOV, and decreased with matrix, pitch and thickness of the scanned objective. The reconstruction algorithm of high resolution results lower low-contrast resolution. Mostly helical image low-contrast resolution is slightly lower than axial image. It's very important for us to understand CT low-contrast resolution and its influencing factors for the correct evaluation of the performance of CT scanner.

Pulse-modulation imaging-review and performance analysis.

In time-domain or pulse-modulation (PM) imaging, the incident light intensity is not encoded in amounts of charge, voltage, or current as it is in conventional image sensors. Instead, the image data are represented by the timing of pulses or pulse edges. This method of visual information encoding optimizes the phototransduction individually for each pixel by abstaining from imposing a fixed integration time for the entire array. Exceptionally high dynamic range (DR) and improved signal-to-noise ratio (SNR) are immediate benefits of this approach. In particular, DR is no longer limited by the power-supply rails as in conventional complementary metal-oxide semiconductor (CMOS) complementary metal-oxide semiconductor active pixel sensors, thus providing relative immunity to the supply-voltage scaling of modern CMOS technologies. In addition, PM imaging naturally supports pixel-parallel analog-to-digital conversion, thereby enabling high temporal resolution/frame rates or an asynchronous event-based array readout. The applications of PM imaging in emerging areas, such as sensor network, wireless endoscopy, retinal prosthesis, polarization imaging, and energy harvesting are surveyed to demonstrate the effectiveness of PM imaging in low-power, high-performance machine vision, and biomedical applications of the future. The evolving design innovations made in PM imaging, such as high-speed arbitration circuits and ultra-compact processing elements, are expected to have even wider impacts in disciplines beyond CMOS image sensors. This paper thoroughly reviews and classifies all common PM image sensor architectures. Analytical models and a universal figure of merit - image quality and dynamic range to energy complexity factor are proposed to quantitatively assess different PM imagers across the entire spectrum of PM architectures.

Dose-time-response cumulative multinomial generalized linear model.

In toxicological and pharmaceutical experiments, a type of quantal bioassay experiment is designed in which a response, such as mortality, in a group of animals is recorded over time points under different dose levels in the course of the experiment. The application of the typical logit and probit analyses is no longer valid in this situation because it neglects the dependency on time and also the possible interaction of time and dose concentration on the response in the experiment. In this paper, a dose-time-response model is proposed for this type of experiment and a cumulative multinomial generalized linear model that incorporates time and the other experimental conditions as covariates is developed by the theory of maximum likelihood estimation. Both the point estimator and confidence bands for ED50(t), the concentration of a toxicant that will kill 50% of the animals by a specific time, t; as well as LT50(d), the time to 50% mortalities for a specific concentration, d, is then formulated in closed form from the newly proposed dose-time-response model. Finally, the newly proposed model is considered for a real data set to demonstrate the application.

[Effects of clonidine on estrus, estradiol, gonadotropin, graafian follicle, and corpus luteum in rats].

Effects of clonidine (Clo) on female reproductive system were studied in rats. Blood FSH, LH, progesterone, testosterone, and estradiol were measured by radioimmunoassay and the development of secondary follicles and corpus luteum in ovary were investigated by morphometry. After Clo po 0.3 mg.kg-1.d-1 x 14 d, the estrus of rats was prolonged; FSH, LH, and progesterone increased significantly; while estradiol reduced. The development of secondary follicles in ovary was blocked at the stage of prematuration and the numerical density of corpus luteum decreased. After clonidine po 28 d, FSH and LH sustained at high levels, but the estrous cycle, estradiol and progesterone recovered.