Parametric analysis of craniocerebral injury mechanism in pedestrian traffic accidents based on finite element methods.

PURPOSE: The toughest challenge in pedestrian traffic accident identification lies in ascertaining injury manners. This study aimed to systematically simulate and parameterize 3 types of craniocerebral injury including impact injury, fall injury, and run-over injury, to compare the injury response outcomes of different injury manners. METHODS: Based on the Total Human Model for Safety (THUMS) and its enhanced human model THUMS-hollow structures, a total of 84 simulations with 3 injury manners, different loading directions, and loading velocities was conducted. Von Mises stress, intracranial pressure, maximum principal strain, cumulative strain damage measure, shear stress, and cranial strain were employed to analyze the injury response of all areas of the brain. To examine the association between injury conditions and injury consequences, correlation analysis, principal component analysis, linear regression, and stepwise linear regression were utilized. RESULTS: There is a significant correlation observed between each criterion of skull and brain injury (p < 0.01 in all Pearson correlation analysis results). A 2-phase increase of cranio-cerebral stress and strain as impact speed increases. In high-speed impact (> 40 km/h), the Von Mises stress on the skull was with a high possibility exceed the threshold for skull fracture (100 MPa). When falling and making temporal and occipital contact with the ground, the opposite side of the impacted area experiences higher frequency stress concentration than contact at other conditions. Run-over injuries tend to have a more comprehensive craniocerebral injury, with greater overall deformation due to more adequate kinetic energy conduction. The mean value of maximum principal strain of brain and Von Mises stress of cranium at run-over condition are 1.39 and 403.8 MPa, while they were 1.31, 94.11 MPa and 0.64, 120.5 MPa for the impact and fall conditions, respectively. The impact velocity also plays a significant role in craniocerebral injury in impact and fall loading conditions (the p of all F test < 0.05). A regression equation of the craniocerebral injury manners in pedestrian accidents was established. CONCLUSION: The study distinguished the craniocerebral injuries caused in different manners, elucidated the biomechanical mechanisms of craniocerebral injury, and provided a biomechanical foundation for the identification of craniocerebral injury in legal contexts.

Importance of optimizing duration of adjuvant immune checkpoint inhibitor therapy to treat postoperative hepatocellular carcinoma after conversion therapy: a case report.

Patients with hepatocellular carcinoma at high risk of recurrence after hepatic resection or local ablation often undergo adjuvant immunotherapy with immune checkpoint inhibitors for 1 year in randomized controlled trials, but the appropriateness of this duration is controversial, especially given the risk of adverse events. Here we report the case of a 52-year-old Chinese man with initially unresectable multinodular recurrent hepatocellular carcinoma who underwent two cycles of transarterial chemoembolization, followed by hepatic resection and 24 months of adjuvant therapy with the PD-1 inhibitor tislelizumab. The patient achieved a recurrence-free survival time of 24 months, but he experienced elevated alpha fetoprotein, Grade 2 hypothyroidism and pruritus while on adjuvant therapy. This case highlights the need to optimize the duration of adjuvant immunotherapy after curative treatment for hepatocellular carcinoma in order to minimize risk of not only recurrence but also adverse events.

Asymmetric gradient orbital interaction of hetero-diatomic active sites for promoting C - C coupling.

Diatomic-site catalysts (DACs) garner tremendous attention for selective CO2 photoreduction, especially in the thermodynamical and kinetical mechanism of CO2 to C2+ products. Herein, we first engineer a novel Zn-porphyrin/RuCu-pincer complex DAC (ZnPor-RuCuDAC). The heteronuclear ZnPor-RuCuDAC exhibits the best acetate selectivity (95.1%), while the homoatomic counterparts (ZnPor-Ru2DAC and ZnPor-Cu2DAC) present the best CO selectivity. In-situ spectroscopic measurements reveal that the heteronuclear Ru-Cu sites easily appear C1 intermediate coupling. The in-depth analyses confirm that due to the strong gradient orbital coupling of Ru4d-Cu3d resonance, two formed *CO intermediates of Ru-Cu heteroatom show a significantly weaker electrostatic repulsion for an asymmetric charge distribution, which result from a side-to-side absorption and narrow dihedral angle distortion. Moreover, the strongly overlapped Ru/Cu-d and CO molecular orbitals split into bonding and antibonding orbitals easily, resulting in decreasing energy splitting levels of C1 intermediates. These results collectively augment the collision probability of the two *CO intermediates on heteronuclear DACs. This work first provides a crucial perspective on the symmetry-forbidden coupling mechanism of C1 intermediates on diatomic sites.

SrCl2·6H2O: An Alkaline-Earth-Metal Chloride Hexahydrate as Deep-Ultraviolet Nonlinear-Optical Crystal with the {[Sr(H2O)6]2+}∞ Cationic Framework.

Exploring deep-ultraviolet (DUV) nonlinear-optical (NLO) materials is significant for the conversion of high-frequency laser. Herein, two alkali-earth-metal halide hexahydrates, SrX2·6H2O (X = Cl, Br), were obtained, and the centimeter-sized single crystals of SrCl2·6H2O were grown by a slow evaporation method. Both of them crystallize in the trigonal space group P321, and their crystal structures show {[Sr(H2O)6]2+}∞ cationic chains, with isolated Cl- or Br- anions interspersed between the chains. SrCl2·6H2O exhibits a moderate second-harmonic-generation response (0.4 × KDP) at 1064 nm and can realize phase matching. Importantly, SrCl2·6H2O has a short ultraviolet cutoff edge (<200 nm). Crystal growth, crystal structures, optical performances, and theoretical calculations of the title and related compounds have been discussed in this work. This study enriches the understanding of metal halide hydrates as NLO materials in the DUV region.

Detection of multiple biomarkers associated with satellite cell fate in the contused skeletal muscle of rats for wound age estimation.

From the perspective of forensic wound age estimation, experiments related to skeletal muscle regeneration after injury have rarely been reported. Here, we examined the time-dependent expression patterns of multiple biomarkers associated with satellite cell fate, including the transcription factor paired box 7 (Pax7), myoblast determination protein (MyoD), myogenin, and insulin-like growth factor (IGF-1), using immunohistochemistry, western blotting, and quantitative real-time PCR in contused skeletal muscle. An animal model of skeletal muscle contusion was established in 30 Sprague-Dawley male rats, and another five rats were employed as non-contused controls. Morphometrically, the data obtained from the numbers of Pax7 + , MyoD + , and myogenin + cells were highly correlated with the wound age. Pax7, MyoD, myogenin, and IGF-1 expression patterns were upregulated after injury at both the mRNA and protein levels. Pax7, MyoD, and myogenin protein expression levels confirmed the results of the morphometrical analysis. Additionally, the relative quantity of IGF-1 protein > 0.92 suggested a wound age of 3 to 7 days. The relative quantity of Pax7 mRNA > 2.44 also suggested a wound age of 3 to 7 days. Relative quantities of Myod1, Myog, and Igf1 mRNA expression > 2.78, > 7.80, or > 3.13, respectively, indicated a wound age of approximately 3 days. In conclusion, the expression levels of Pax7, MyoD, myogenin, and IGF-1 were upregulated in a time-dependent manner during skeletal muscle wound healing, suggesting the potential for using them as candidate biomarkers for wound age estimation in skeletal muscle.

Assessment of probiotic adhesion and inhibitory effect on Escherichia coli and Salmonella adhesion.

In this study, we screened bacterial strains to identify specific probiotics to treat pig diarrhea caused by Escherichia coli or Salmonella. The potential probiotics were assayed for their survival in gastrointestinal solution, their antimicrobial activity, cell-surface properties, adhesion to Caco-2 cells, and inhibition of pathogen adhesion. Nine out of the 20 strains tested showed high tolerance of a simulated gastrointestinal environment and six strains exerted antagonistic effects against enterohemorrhagic E. coli (EHEC) O157:H7 and Salmonella Typhimurium MQ. Lactobacillus johnsonii pDX1e exhibited a higher potent antibacterial activity. Four strains (pDX1a, pDX1e, pDX3a, and pDX5a) displayed auto-aggregation, hydrophobicity, and adhesion to Caco-2 cells similar to those of the reference strain Lacticaseibacillus rhamnosus GG (LGG). Enterococcus durans pDX5a showed the highest adhesion capacity (13.86%), followed by the reference strain LGG (11.20%). All the tested strains competitively suppressed the attachment of pathogens to Caco-2 cells (by 30.73-55.18%); L. johnsonii pDX1e and Ent. durans pDX5a significantly inhibited the adhesion of pathogens by substitution and exclusion, respectively. Therefore, pDX1e and pDX5a were selected as probiotic strains for further investigation and application.

Determination of urinary carnitine levels as a potential indicator of uterine fibroids caused by nonylphenol exposure.

Our previous studies have shown that uterine fibroids are associated with nonylphenol (NP) exposure, and the changes of carnitines in critical reproductive tissues and body fluids could be used to indicate the female reproductive toxicity caused by NP exposure. In this work, on the basis of further clarifying the correlation between NP exposure level and uterine fibroids, the possibility of the urinary carnitine levels as a potential indicator of uterine fibroids caused by NP exposure was discussed. The urine samples were collected from 84 female volunteers: the control group of 34 healthy women without gynecological disease and 50 uterine fibroids patients, respectively. Methods were respectively established for the determination of NP and eight carnitines in human urine samples by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The results showed that the NP level of uterine fibroids group was significantly higher than that of control group (P = 0.002), indicating that NP exposure was an important environmental factor in the occurrence of uterine fibroids. It was further found that in urine samples of the uterine fibroids group, the levels of L-Carnitine (C0), L-Acetyl-carnitine (C2), L-Octanoyl-carnitine (C8), Tetradecanoyl-carnitine (C14), Oleoyl-carnitine (C18:1) and Linoleoyl-carnitine (C18:2) had obviously increased compared with those in the control group (P < 0.001; < 0.001; < 0.001; = 0.003; < 0.001; = 0.010). The concentrations of L-Hexanoyl-carnitine (C6) and L-Palmitoyl-carnitine (C16) in the uterine fibroids group were also higher than those in the control group, although the difference was not statistically significant (P > 0.05). The results suggested that the changes in urinary carnitine levels might be a potential indicator to help to warn of the risk of uterine fibroids caused by NP exposure at the early stage.

Sleep quality and health service utilization in Chinese general population: a cross-sectional study in Dongguan, China.

OBJECTIVES: The aims of this study were to explore the Pittsburgh Sleep Quality Index (PSQI) and health service utilization in Chinese general population, to investigate the association between PSQI and health service utilization and to identify the independent contributions of social demographic variables, health related factors and PSQI to health service utilization. METHODS: In a cross-sectional community-based health survey using a multi-instrument questionnaire, 4067 subjects (≥15 years old) were studied. The Chinese version of the PSQI was used to assess sleep quality. Health service utilization was measured by recent two-week physician visit and annual hospitalization rates. RESULTS: Higher PSQI scores were associated with more frequent health service utilization. Higher scores in subjective sleep quality were associated with higher rate of recent two-week physician visit (adjusted OR = 1.24 per SD increase, P = 0.015). Higher scores in habitual sleep efficiency (adjusted OR = 1.24 per SD increase, P = 0.038) and sleep disturbances (adjusted OR = 2.09 per SD increase, P < 0.001) were associated with more frequent annual hospitalization. The independent influence of PSQI on the risk of recent two-week physician visit was 0.7%, and that of annual hospitalization 31.4%. CONCLUSIONS: Poorer sleep quality predicted more frequent health service utilization. The independent contribution of PSQI on health service utilization was smaller than social demographic variables.

[FTIR spectra study on the swellbility and controlled-release mechanism of polyurethane coated urea].

The nutrient release experiment of polyurethane coated urea (PCU) was carried out in pure water at 25 degrees C. With the release of urea, the structural variation of polyurethane coating was investigated by Fourier transform infrared spectroscopy (FTIR), then a series of curves were collated and compared so as to better reflect the relation between diffusion rate of urea and coating structure. It was found that when the nutrient was released by 50% wt, new absorption peaks at 3 435, 3 342, 1 671, 1 621, 1 448 and 1 159 cm(-1) appear in the FTIR spectra of polyurethane coating, moreover, the height of these absorption peaks was increased gradually when the nutrient was released by 70% wt, more importantly, these new absorption peaks are consistent with the characteristic absorption peaks of urea fertilizer, the spectra of urea were mainly characterized by bands at 3 440, 3 346, 1 672, 1 621 and 1 461 cm(-1). The results show that the IR spectra variation was caused by the content of urea, existing in the polyurethane coating, and was increased gradually, The more the urea content, the greater the swelling degree of the polyurethane coating. The swelling of polyurethane coating leads to the pores size change, and release rate is increased, so the "S" pattern curve of the nitrogen accumulative release is formed.

[Study on immune status of patients with schistosomiasis japonica in Poyang Lake region I characterization of antigen-specific antibody isotype responses to Schistosoma japonicum].

OBJECTIVE: To understand the characterization and levels of antibody isotype responses to soluble egg antigen (SEA) and adult worm antigen (AWA) of Schistosoma japonicum in schistosomiasis patients in Poyang Lake region. METHODS: Antibody isotype IgG, IgG1, IgG2, IgG3, IgG4, IgE, IgM and IgA responses to SEA and AWA in the sera of individuals from endemic and non-endemic areas were determined by indirect ELISA. RESULTS: The levels of antigen-specific antibody isotypes in the sera of patients with egg positive were significantly higher than those of people with egg negative and normal control population from non-endemic area (P < 0.001), and except for anti-SEA IgG2 and anti-AWA IgG4 and IgE antibodies, the levels of antibody isotypes in the sera of people with egg negative in endemic area were significantly higher than those of normal control population from non-endemic area (P < 0.05). In the population with egg positive, children had higher levels of anti-SEA IgM and IgG1 and anti-AWA IgM antibody, and lower AWA specific IgG than adults. There was no significant difference between the male and female except for the male had higher levels of IgG (F = 4.677, P = 0.032) and IgG1 (F = 5.55, P = 0.020)against AWA. Three months post-treatment, the levels of IgG1, IgG3, IgG4 antibody responses to SEA deceased significantly (P < 0.001, P = 0.029, P = 0.044), and almost all the antibody levels decreased significantly (P < 0.05) twelve months post-treatment, except for SEA specific IgE and IgM and AWA specific IgG4 and IgM antibodies. CONCLUSIONS: The levels of antigen-specific antibody isotypes in the sera of patients with egg positive are significantly higher than those of people with egg negative and normal control population from non-endemic area. Almost all of antibody levels decrease significantly twelve months post-treatment. The levels of antibody isotypes in the sera of people with egg negative in endemic area are significantly higher than those of population from non-endemic area, giving a clue that the selection of negative control of schistosomiasis diagnostic kit should be noticed.

[Surveillance of schistosomiasis in Zhuxi Village, Xingzi County, 2005-2010].

OBJECTIVE: To understand the effect of schistosomiasis control in Zhuxi Village, Xingzi County, Jiangxi Province. METHODS: According to the national scheme of schistosomiasis surveillance, we investigated the schistosomiasis epidemic in Zhuxi Village from 2005-2010. The epidemic data of schistosomiasis on the humans, farm cattle, and Oncomelania snails were collected, respectively and analyzed by using the method of Cochran-Armitage test. RESULTS: Human infections and snail infections showed dynamic fluctuations (Z = 3.35, P = 0.000 8) and the density of alive snails tended to decrease gradually. The majority of the infections were peasants and students. The infection rates of farm cattle were 12.31%, 3.23%, 2.94%, 3.33%, 4.44% and 2.15%, respectively from 2005-2010. CONCLUSION: The effect of schistosomiasis control is very fine and schistosomiasis has been well controlled.

[FTIR spectra study on the film of polyurethane coated urea controlled-release fertilizer].

The polyurethane films were prepared to wrap the urea in order to achieve a desirable release rate by mixing isocyanate, polyols and wax. The effect of wax, urea and isocyanate on the structure and properties of the films was investigated by FTIR. The structural changes were monitored as the polyurethane films together with the wrapped urea were immersed into ammonia water for 28 days, which is used to model soil conditions. The FTIR results showed that the width and intensity of the NH-free band increased remarkably with time, and all kinds of carbonly bands shifted to high wavenumber and their intensity increased obviously. The results suggest that the structure of the polyurethane films was destroyed more heavily in soil than in water, and this explains the relatively fast release rate of urea in soil. It was observed that the increase in the chemical crosslinking density in the polyurethane films can effectively decrease the release rate of the urea nitrogen in soil.

[Evaluation on application of common diagnosis methods for schistosomiasis japonica in endemic areas of China. III. Analysis and evaluation of underestimation of prevalence of Schistosoma japonicum infection by routine Kato-Katz technique].

OBJECTIVE: To understand the rates of underestimation of Schistosoma japonicum infection by Kato-Katz technique with different stool samples and different smears in field site. METHODS: With 27 Kato-Katz thick smears (3 stool samples with 9 thick smears each) for 3 consecutive years as a "gold standard", the rates of underestimation of schistosome infection by Kato-Katz technique with different stool samples and different smears were evaluated in a schistosomiasis endemic village. RESULTS: The examined rates of schistosome infection increased and the rates of underestimation decreased gradually with the increase of the number of Kato-Katz thick smears examined. The rates of underestimation of 3 smears were 40.98%-50.80% and the rates of underestimation of 6 smears were 25.48%-32.39%. The rates of schistosome infection based on the reading of 27 Kato-Katz thick smears were 10.96% in 2008, 8.54% in 2009 and 3.73% in 2010 respectively, but the rates of underestimation of various Kato-Katz thick smears were similar. There were no significant differences among the readings of 3, 6, and 9 smears of 1 stool sample, 3, 6 and 9 smears of 3 stool samples, 6 smears of 2 stool samples, 6 smears of 1 stool sample, and 6 smears of 3 stool samples. CONCLUSIONS: In a community with low-intensity of schistosome infection, the rate of underestimation is big by Kato-Katz technique with the reading of 3 smears of 1 stool sample. It suggested that it is better to increase smears rather than the number of stool samples examined.

[Mutation analysis of the eda-A1 gene for hypohidrotic ectodermal dysplasia and construction of recombined eukaryotic expression vector].

OBJECTIVE: The purpose of this study was to clone and analyze mutation in the eda-A1 gene for hypohidrotic ectodermal dysplasia (HED), and to construct a new recombined eukaryotic expression vector (mutant M, wild W) as a basis for further study on the genetic function. METHODS: After total mRNA was extracted from peripheral blood lymphocytes from the HED affect patient and control, eda-A1 gene was amplified by reverse transcription polymerase chain reaction (RT-PCR) with a pair of specific primers containing the constriction enzyme sites of BamH I and Hind III. When the vector pcDNA3.1(-) and eda-A1 (M/W) were digested by BamH I and Hind III respectively, eda-A1 (M/W) fragment was then ligated to vector pcDNA3.1 (-) and the new vector was named as pcDNA3.1 (-)-eda-A1-M/W. RESULTS: eda-A1 gene was successfully cloned and a novel missence mutation was identified, which changes the codon 306 from glutamine to proline. PCR, restrictive endonuclease analysis and DNA sequencing were then performed to identify the recombinant eukaryotic expression vector pcDNA3.1 (-)-eda-A1-M/W, and the results were surely confirmed. CONCLUSION: Our result indicates that the novel missense mutation in eda is associated with the isolated tooth agenesis and provide preliminary explanation for the abnormal clinical phenotype at a molecular structural level. And also, the recombinant eukaryotic expression vector pcDNA3.1 (-)-eda-A1-M/W was successfully constructed, which will be thereafter taken use of further study on eda gene in odontogenesis.

Controlled immobilization of chondroitin sulfate in polyacrylic acid networks.

Novel semi-interpenetrating polymer networks (semi-IPNs) of chondroitin sulfate (ChS) and acrylic acid (AA) were prepared with the aim of obtaining a hydrogel for use as a colon-specific drug carrier. By controlling the concentrations of cross-linking agent, diethylene glycol dimethacrylate (DEGDA), as well as the reaction solvent, high swelling percentages were obtained (approx. 1600%). However, the highest sol percent obtained for these hydrogels was approx. 70%, and most of the chondroitin sulfate remained soluble and could be extracted. Therefore, an alternative approach was adopted: methacrylate-grafted ChS (ChSMA) was synthesized and then co-polymerized with acrylic acid (AA) at a molar ratio of 1:5 with various concentrations of AA. The sol content of these ChSMA-AA hydrogels was reduced to approx. 20%, and the cross-linking densities were almost 100-fold higher than those of the semi-IPNs. FT-IR spectra showed that the H-bonding interactions between ChS and PAA and the spectra of the semi-IPNs were similar to that of PAA itself after sol extraction. In contrast, the FT-IR spectra of ChSMA-AA remained intact after sol extraction. Ketoprofen was used as a model drug to test the sustained release behavior of these hydrogels.

Effects of serum containing Xinlikang on angiotensin ii induced hypertrophy in cultured neonatal rat cardiomyocytes.

OBJECTIVE: To evaluate the effects of Xinlikang (XLK) on angiotensin II (Ang II) induced hypertrophic cultured neonatal rat's cardiomyocyte (CMC). METHODS: Primary cultured neonatal rat's CMCs with the purity certified by immunohistochemical technique, were divided into three groups. Rats in the normal control group were untreated; those in the model group were established into hypertrophic models but underwent no treatment; and those in the XLK group were established to hypertrophic models and treated with XLK containing serum obtained from rats with aorta coarctation after 8 days of feeding with XLK. MTT and phase-contrast microscope were used to evaluate the effect of XLK on cell activity, pulsating rhythm and surface area; Atrial natriuretic peptide (ANP) expression was determined by radioimmunoassay; Protein content was determined by Bradford method; and DNA synthesis was detected by flow cytometric assay. RESULTS: Immunohistochemistry results showed that more than 90% of the cells were alpha-sarcometin actin stained positive cells. No significant effect of XLK on normal CMC was found. Ang II could significantly induce hypertrophy in CMCs, and XLK could significantly decrease the increased surface area and the accelerated pulsating rate in them. ANP expression was 780 +/- 38 microg/L in the model group, and 430 +/- 23 microg/L in the control group, and the elevated expression of ANP in model rats was significantly decreased in the XLK group; The DNA content in the G0/G1 and G2/M phases was significantly enhanced and at the same time it was accompanied with increase of total protein content in the model rats after being stimulated by Ang II for 24 h, showing that serum-containing XLK could also significantly suppress total protein synthesis (P < 0.05). CONCLUSION: XLK could improve Ang II mediated pathological growth of CMCs without influencing the growth of normal CMCs, suggesting that XLK is probably an effective drug for treatment of myocardial hypertrophy and heart failure.

Mesenteric artery remodeling and effects of imidapril and irbesartan on it in spontaneously hypertensive rats.

AIM: To investigate the remodeling of mesenteric artery and the expression of TGF-beta1, c-Jun in mesenteric artery and effects of imidapril and irbesartan on the remodeling in spontaneously hypertensive rats (SHR). METHODS: Thirty SHR (male/female, 21/9), aged 13 wk, were randomly divided into 3 groups (7 male rats and 3 female rats each group): SHR group, imidapril group (imidapril 3 mg/kg.d was given in drinking water for 14 wk), and irbesartan group (irbesartan 50 mg/kg.d was given in drinking water foe 14 wk). Ten homogeneous Wistar Kyoto rats, 5 males and 5 females, weighing 206+/-49 g, were selected as normal control group (WKY group). Systolic pressure was measured on d 1, 2, 4, 6, 8, 10, 12 and 14 during the experiment and the rats were killed at the end of the experiment. Angiotensin II (Ang II) level in plasma and mesenteric arteries was measured by radioimmunoassay. The morphology of the secondary branches of mesenteric artery were examined by light microscopy and electron microscopy. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of transforming growth factor TGF-beta1 and c-Jun mRNA. RESULTS: Compared with imidapril group and irbesartan group, the blood pressure was remarkably increased in SHR group. Ang II level in plasma and mesenteric arteries in SHR group was the same or lower than that in WKY group, and was higher in irbesartan group and lower in imidapril group. The remodeling of mesenteric arteries in SHR group was mostly obvious among the 4 groups. The ratio of TGF-beta1 absorbed light value to GAPDH absorbed light value in the SHR group was 0.887+/-0.019, which was significantly higher than that in WKY group, imidapril group, and irbesartan group with the ratios of 0.780+/-0.018, 0.803+/-0.005, and 0.847+/-0.017, respectively (P<0.01). Ang II level in plasma and mesenteric arteries in imidapril group was significantly lower than that in irbesartan group (P<0.05). The c-Jun absorbed light value/GAPDH absorbed light value of mesenteric arteries in the SHR group was 0.850+/-0.015, which was significantly higher than that in the WKY, imidapril, and irbesartan groups (0.582+/-0.013, 0.743+/-0.012, and 0.789+/-0.013, respectively, P<0.01), and was significantly lower in imidapril group than in irbesartan group (P<0.05). CONCLUSION: Imidapril and irbesartan can not only control blood pressure but also inhibit mesenteric arteries remodeling and mRNA expression of TGF-beta1, c-Jun in SHR. Imidapril is more effective than irbesartan.

Diverse effects of long-term treatment with imidapril and irbesartan on cell growth signal, apoptosis and collagen type I expression in the left ventricle of spontaneously hypertensive rats.

To compare diverse effects of angiotensin II type 1 receptor antagonists (irbesartan) and angiotensin converting enzyme inhibitors (imidapril) on left ventricular remodeling in spontaneously hypertensive rats (SHR). Thirty male SHR were randomly divided into three groups: SHR-IR (treated with irbesartan, 50 mg/kg), SHR-IM (imidapril, 3 mg/kg), SHR-C (placebo). Ten male Wistar Kyoto rats (WKY) treated with placebo acted as the control. All treatments were administered once daily from 14 to 27 weeks of age. Imidapril and irbesartan have the similar inhibitor effects on blood pressure and left ventricular mass indexes in SHR. Despite both drugs suppressed ERK-1 protein expression, decreased cardiomyocytes apoptosis index, blocked collagen type I deposition, reduced TGF-beta(1) gene expression in SHR, imidapril elicits a stronger inhibitory effect. Irbesartan had little effect on MKP-1 protein expression, but imidapril decreased it significantly. As a result, the ERK-1/MKP-1 ratio in SHR-IR was significantly greater than that in SHR-IM (P < 0.05). These results suggest that the balance between MKP-1 and ERKs in myocardial tissue is important for cardiac cell proliferation and growth. They also indicate that the similar efficacy of antihypertensive treatment in reducing blood pressure does not predict the similar capacity to control the individual facet of left ventricular remodeling. Irbesartan is more effective in regressing the homeostasis between ERK-1 and MKP-1, however imidapril is superior in suppressing apoptosis and collagen synthesis in cardiac tissue.

Effect of angiotensin II receptor 1 antisense oligodoexynucleotides on physiological and pathophysiological growth of cardiomyocytes.

AIM: To evaluate the role of angiotensin II receptor 1 antisense oligodexynucleotides (AT1R-AS-ODNs) on physiological and pathophysiological growth of cardiomyocytes from normotensive rats. METHODS: Cardiomyocytes were transfected with AT1R-AS-ODNs (200 nmol/L) followed by treatment with or without angiotensin II (1 micromol/L). In situ hybridization and Western blot were used for AT1R mRNA and protein detection, respectively. c-Jun N-terminal protein kinase (JNK) activity was characterized by immune complex kinase assay. c-Jun protein expression was examined by immunocytochemistry. DNA content was detected by flow cytometric assay. Atrial natriuretic factor (ANF) expression was identified by radioimmunoassay. RESULTS: Treatment with AT1R-AS-ODNs for 24 h resulted in 51.2 % decrease in AT1R mRNA and 60.7 % in protein (P<0.05 vs control). However, the basal level of JNK activity, c-Jun protein expression, and DNA content were not altered by AT1R-AS treatment in absence of overactive hormonal system. After treatment with angiotensin II for 30 min, both p46JNK and p54JNK were robustly activated. By 2 h, c-Jun protein expression was increased. By 24 h, angiotensin II caused a marked increase both in G0/G1 and G2/M DNA content, and increased ANF expression by 1.8-fold. All these were inhibited by AT1R-AS-ODNs pretreatment. In contrast, sense sequence was ineffective. CONCLUSION: Decrease of AT1R expression by AS-ODNs did not interfere with normal growth, but protected cardiomyocytes from angiotensin II-dependent pathophysiological growth.

In vivo protective effect of protocatechuic acid on tert-butyl hydroperoxide-induced rat hepatotoxicity.

Increasing evidence regarding free-radical generating agents and the inflammatory process suggests that accumulation of reactive oxygen species (ROS) can involve hepatotoxicity. Previously, we found that protocatechuic acid (PCA), a polyphenolic compound from Hibiscus sabdariffa L. possessing free radical-scavenging capacity, protected against oxidative damage induced by tert-butylhydroperoxide (t-BHP) in rat primary hepatocytes. In this study, first PCA was evaluated by its capacity of inhibiting xanthine oxidase (XO) and lipoxygenase (LO) activity in vitro, then it was used to induce hepatotoxicity to assess the antioxidant and anti-inflammatory bioactivity of PCA in vivo. Our investigation showed that pretreatment with PCA (50-100 mg/kg) by gavage for 5 days before a single dose of t-BHP (ip; 0.2 mmol/kg ) significantly lowered serum levels of the hepatic enzyme markers lactate dehydrogenase (LDH) and alanine (ALT) and aspartate (AST) aminotransferase, and reduced oxidative stress of the liver by evaluating malondialdehyde (MDA) and glutathione (GSH). Histopathological evaluation of the rat livers revealed that PCA reduced the incidence of liver lesions, including hepatocyte swelling, leukocyte infiltration, and necrosis induced by t-BHP. In addition, PCA inhibited t-BHP-induced tyrosine phosphorylation, an implication of the activation of a stress signal pathway, in the liver. These results indicate that PCA protects against t-BHP-induced hepatotoxicity by its antioxidant and anti-inflammatory characteristics accompanied by blocking of stress signal transduction.