Search

Early-onset neonatal sepsis (EONS), a bacterial infection that occurs within 72 h after birth, is associated with high likelihood of neonatal mortality. Latamoxef, a semi-synthetic oxacephem antibiotic developed in 1980s, has been brought back into empirical EONS treatment in recent years. In the preliminary work, we established a population pharmacokinetics (PPK) model for latamoxef in Chinese neonates. Moreover, in order to better guide clinical treatment, we conducted dose simulation and found that ascending administration frequency could improve the target rate of 70% of patients having a free antimicrobial drug concentration exceeding the MIC during 70% of the dosing interval (70% fT > MIC). Accordingly, this study is aimed to compare the 70% fT > MIC, efficacy and safety between conventional regimen and PPK model regimen for rational use of latamoxef in EONS treatment. A single-blind, multicenter randomized controlled trial (RCT) for latamoxef will be conducted in Chinese EONS patients. Neonates (≤3 days of age, expected number = 114) admitted to the hospital with the diagnosis of EONS and fulfilling inclusion and exclusion criteria will be randomized (ratio of 1:1) to either a conventional regimen (30 mg/kg q12h) or model regimen (20 mg/kg q8h) latamoxef treatment group for at least 3 days. Primary outcome measure will be 70% fT > MIC and secondary outcome indicators will be the latamoxef treatment failure, duration of antibiotic therapy, changes of white blood cell count (WBC), C-reactive protein (CRP) and procalcitonin (PCT), blood culture results during administration and incidence of adverse event (AE)s. Assessments will be made at baseline, initial stage of latamoxef treatment (18–72 h) and before the end of latamoxef treatment. Ethical approval of our clinical trial has been granted by the ethics committee of the Beijing Children’s Hospital (ID: 2020-13-1). Written informed consent will be obtained from the parents of the participants. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR 2000040064).It is hoped that our study will provide a clinical basis for the rational clinical use of latamoxef in EONS treatment.

BackgroundThis meta-analysis of prospective observational studies and randomized controlled trials (RCTs) was carried out to explore the association between selenium and the risk of cardiovascular disease (CVD) and all-cause mortality.Methods and Study DesignWe searched the PubMed, EMBASE and Web of Science database for eligible studies which included the relationship between selenium and the outcomes of interest. 25 prospective observational studies and 9 RCTs were included in our meta-analysis.ResultsThe observational studies showed that there was a significant inverse association between serum selenium and the risk of CVD (RR: 0.78; 95% CI: 0.68–0.89), coronary heart disease (CHD) (RR: 0.75; 95% CI: 0.58–0.95) and all-cause mortality (RR: 0.77; 95% CI: 0.71–0.84). We also found a significant inverse association between selenium supplements and the risk of total CVD (RR: 0.78; 95% CI: 0.62–0.98) and all-cause mortality (RR: 0.81; 95% CI: 0.65-1.00) in RCTs studies.ConclusionsOur meta-analysis found a significant inverse association between selenium and CVD, CHD, and all-cause mortality in prospective observational studies and RCTs, which indicate the selenium has protective effect in cardiovascular disease and all-cause mortality.

Renal impairment (RI) is known to influence the pharmacokinetics of nonrenally eliminated drugs, although the mechanism and clinical impact is poorly understood. We assessed the impact of RI and single dose oral rifampin (RIF) on the pharmacokinetics of CYP3A, OATP1B, P-gp, and BCRP substrates using a microdose cocktail and OATP1B endogenous biomarkers. RI alone had no impact on midazolam (MDZ), maximum plasma concentration (Cmax ), and area under the curve (AUC), but a progressive increase in AUC with RI severity for dabigatran (DABI), and up to ~2-fold higher AUC for pitavastatin (PTV), rosuvastatin (RSV), and atorvastatin (ATV) for all degrees of RI was observed. RIF did not impact MDZ, had a progressively smaller DABI drug-drug interaction (DDI) with increasing RI severity, a similar 3.1-fold to 4.4-fold increase in PTV and RSV AUC in healthy volunteers and patients with RI, and a diminishing DDI with RI severity from 6.1-fold to 4.7-fold for ATV. Endogenous biomarkers of OATP1B (bilirubin, coproporphyrin I/III, and sulfated bile salts) were generally not impacted by RI, and RIF effects on these biomarkers in RI were comparable or larger than those in healthy volunteers. The lack of a trend with RI severity of PTV and several OATP1B biomarkers, suggests that mechanisms beyond RI directly impacting OATP1B activity could also be considered. The DABI, RSV, and ATV data suggest an impact of RI on intestinal P-gp, and potentially BCRP activity. Therefore, DDI data from healthy volunteers may represent a worst-case scenario for clinically derisking P-gp and BCRP substrates in the setting of RI.

Background Recent studies have shown that amyloid-β (Aβ) burden influenced white matter (WM) integrity before the onset of dementia. Objective To assess whether the effects of Aβ burden on WM integrity in cognitively normal (CN) individuals were regionally specific. Methods Our cohort consisted of 71 CNs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database who underwent both AV45 amyloid-PET and diffusion tensor imaging. Standardized uptake value ratio (SUVR) was computed across four bilateral regions of interest (ROIs) corresponding to four stages of in vivo amyloid staging model (Amyloid stages I-IV). Linear regression models were conducted in entire CN group and between APOEɛ4 carriers and non-carriers. Results Our results indicated that higher global Aβ-SUVR was associated with higher mean diffusivity (MD) in the entire CN group (p = 0.023), and with both higher MD (p = 0.015) and lower fractional anisotropy (FA) (p = 0.026) in APOEɛ4 carriers. Subregion analysis showed that higher Amyloid stage I-II Aβ-SUVRs were associated with higher MD (Stage-1: p = 0.030; Stage-2: p = 0.016) in the entire CN group, and with both higher MD (Stage-1: p = 0.004; Stage-2: p = 0.010) and lower FA (Stage-1: p = 0.022; Stage-2: p = 0.014) in APOEɛ4 carriers. No associations were found in APOEɛ4 non-carriers and in Amyloid stage III-IV ROIs. Conclusions Our results indicated that the effects of Aβ burden on WM integrity in CNs might be regionally specific, particularly in Amyloid stage I-II ROIs, and modulated by APOEɛ4 status.

Using a sandwich-type immunoassay, a novel electrochemical immunosensor based on the successful preparation of a hexestrol (HEX) monoclonal antibody was successfully constructed to detect four phenolic oestrogens: HEX, diethylstilboestrol (DES), dienestrol (DE) and bisphenol A (BPA). An innovative strategy to design the HEX monoclonal antibody/mercapto acetic acid (MACA)/nanogold immunosensor was developed by combining a nanosized effect, self-assembly and specific immune technology. The differential pulse voltammetry (DPV) response for four phenolic oestrogens was in the order BPA > DE > HEX > DES with detection limits of 0.037, 0.047, 0.052 and 0.060 ng mL−1, respectively (S/N = 3). This immunosensor exhibits superior electrochemical properties with a wide linear range, low detection limit, excellent reproducibility and high selectivity. Compared with a high-performance liquid chromatography method, a high accuracy of DES detection in beef, duck and milk powder samples was achieved by the immunosensor proposed, which exhibits great potential for the detection of phenolic oestrogens in applications in environmental and food safety.

Lipopolysaccharide (LPS) can induce bone loss by stimulating osteoclast formation. Colony-stimulating factor 1 receptor (CSF 1R) inhibitors have great potential for the treatment of rheumatoid arthritis and tumor-related bone erosion. However, its role in LPS-induced bone loss is still not clarified. In this study, we observed the effects of CSF 1R inhibitor, PLX3397, on LPS-induced bone damage in an animal model. The models were established by LPS administration in male Sprague-Dawley rats. PLX3397 (30 mg/kg body weight) was given by oral gavage. MicroCT analysis, biomechanical properties, biomarker assay, histological examination, and mRNA expression of osteoclast differentiation-related genes (Traf6, Fra1, c-fos and NFATc1) were performed on the 8th week. LPS induced bone loss was shown as the decrease in bone volume fraction and trabecular number and increase in trabecular separation (p

Mutant Huntingtin (mtHtt) causes neurodegeneration in Huntington's disease (HD) by evoking defects in the mitochondria, but the underlying mechanisms remains elusive. Our proteomic analysis identifies valosin-containing protein (VCP) as an mtHtt-binding protein on the mitochondria. Here we show that VCP is selectively translocated to the mitochondria, where it is bound to mtHtt in various HD models. Mitochondria-accumulated VCP elicits excessive mitophagy, causing neuronal cell death. Blocking mtHtt/VCP mitochondrial interaction with a peptide, HV-3, abolishes VCP translocation to the mitochondria, corrects excessive mitophagy and reduces cell death in HD mouse- and patient-derived cells and HD transgenic mouse brains. Treatment with HV-3 reduces behavioural and neuropathological phenotypes of HD in both fragment- and full-length mtHtt transgenic mice. Our findings demonstrate a causal role of mtHtt-induced VCP mitochondrial accumulation in HD pathogenesis and suggest that the peptide HV-3 might be a useful tool for developing new therapeutics to treat HD., Mitochondria defects caused by mutant huntingtin (mtHtt) have been implicated in Huntington's disease. Here authors show that VCP binds to mtHtt on the mitochondria, and that treatment with a peptide that disrupts this interaction reduces the cellular and behavioural deficits in mouse models of HD.

Chronic hepatitis B virus (HBV) infection (CHB) is a major cause of cirrhosis and hepatocellular carcinoma (HCC). Although the availability of HBV vaccines effectively reduces the incidence of HBV infection, the healthcare burden from CHB remains high. Several antiviral agents, such as (pegylated-) interferon-α and nucleos(t)ide analogs are approved by US FDA for chronic HBV infection management. Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have been recommended as the first-line anti-HBV drugs for excellent viral suppression with a low risk of antiviral resistance, but the cost and need for essentially life-long treatment are considerable challenges. And none of these current treatments can eradicate the intracellular virus. Given these issues, there is still an unmet medical need for an efficient HBV cure. We summarize here the key developments of antivirals against hepatitis B virus, including HBV replication cycle inhibitors and host immune regulators.

Since December 2019, there has been an outbreak of novel coronavirus (2019-nCoV) infection in China. Two cases of neonates with positive 2019-nCoV tests have been reported. Due to the immature immune system and the possibility of vertical transmission from mother to infant, neonates have become a high-risk group susceptible to 2019-nCoV, which emphasize a close cooperation from both perinatal and neonatal pediatrics. In neonatal intensive care unit (NICU), to prevent and control infection, there should be practical measures to ensure the optimal management of children potentially to be infected. According to the latest 2019-nCoV national management plan and the actual situation, the Chinese Neonatal 2019-nCoV expert working Group has put forward measures on the prevention and control of neonatal 2019-nCoV infection.

In this paper, using a indirect competitive immunoassay, a electrochemical immunosensor based on hexestrol (HEX)-2-aminoethanethiol hydrochloride (AET)-gold nanoparticles (Au NPs)-glassy carbon electrode (GCE) was favorably prepared to simultaneous detection four phenolic estrogens: HEX, diethylstilbestrol (DES), dienestrol (DE) and bisphenol A (BPA). The HEX-AET-Au NPs-GCE was characterized by scanning electron microscopy (SEM), infrared spectrum (IR) and electrochemical impedance spectroscopy (EIS). A design strategy of HEX-AET-Au NPs-GCE was introduced by nano-sized effect, self-assembly and specific immune technology. The amperometric response sequence was DES > DE > BPA > HEX by differential pulse voltammetry (DPV) with detection limits of 0.25, 0.15, 0.20 and 0.25 ng⋅mL−1, respectively (S/N = 3), which indicates satisfactory linear range and selectivity. Compared with HPLC-MS/MS method, the accuracy of DE detection in real samples was carried out by the HEX-AET-Au NPs-GCE, which displays potential applications in phenolic estrogens detection of environment and food.

Hepatitis B virus (HBV) belongs to the Hepadnaviridae family. HBsAg, greatly outnumbered mature virion, has been mysterious since the discovery of HBV. A novel benzimidazole derivative, BM601, is identified inhibiting the secretion of HBV virions and HBsAg, with 50% effective concentration of 0.6μM and 1.5μM, as well as 50% cytotoxicity concentration of 24.5μM. It has no effect on transcription, protein production, nucleocapsid formation or intracellular HBV DNA synthesis. Immunofluorescence analysis suggests that BM601 might inhibit virion and HBsAg secretion by interfering surface protein aggregation in trans Golgi apparatus. Furthermore, BM601 does not trigger cellular stress response or affect HBeAg or host protein secretion. We hypothesize that BM601 is a secretion inhibitor functioning at the level of virion and HBsAg secretion pathway.

The capsid of hepatitis B virus (HBV) plays a vital role in virus DNA replication. Targeting nucleocapsid function has been demonstrated as an effective approach for anti-HBV drug development. A high-throughput screening and mechanism study revealed the hit compound 4a as an HBV assembly effector (AEf), which could inhibit HBV replication by inducing the formation of HBV DNA-free capsids. The subsequent SAR study and drug-like optimization resulted in the discovery of the lead candidate 4r, with potent antiviral activity (IC50 = 0.087 ± 0.002 μM), low cytotoxicity (CC50 = 90.6 ± 2.06 μM), sensitivity to nucleoside analogue-resistant HBV mutants, and synergistic effect with nucleoside analogues in HepG2.2.15 cells.

To improve the properties of gelatin, oxidized starch (OS) with different carbonyl content was introduced into the gelatin. In this study, we researched the influence of the carbonyl content of OS on the rheological characteristics, swelling behavior, thermal properties, and wettability of the modified gelatin film (MGF). The MGF samples were prepared by the casting of a 10% w/w solution of gelatin and OS with 18.9, 38.7, and 49.3% carbonyl content, respectively. The results of the dynamic viscosity demonstrated that the influence of the temperature on the rheological characteristics of native gelatin film (NGF) was more obvious than that of MGF. Meanwhile, the viscosity of the samples decreased with increasing carbonyl content in OS. Both the differential scanning calorimetry and thermogravimetry curves indicated that the denaturation and pyrogenic decomposition temperatures of the MGF samples were higher than those of NGF; this meant that the crosslinking between NGF and OS improved the physicochemical properties of gelatin. Compared with the NGF sample, MGF was less hydrophilic because the hydrophilic groups of gelatin could be shielded by OS. Meanwhile, the acid–base and salt sensitivity of the MGF samples were very obvious; therefore, the MGF samples could potentially be used as biomedical materials. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 3809–3815, 2013

Using hydrogen peroxide as oxidant, the chitin has been oxidized under a certain conditions. And then the IR and SEM of product has been tested, and the results show that hydroxyl group can be transform carbonyl group. What’s more, the oxidation reaction occurred not only in the surface of chitin, but also in its interior. Owing to the reaction of carbonyl group in the oxidation product, this chitin derivatives was applied to cross link with gelatin material, and the properties of modified gelatin film then has been tested. The results of Differential Scanning Calorimeter (DSC) show that the denaturation temperature of composite gelatin film has been enhanced to 109.8°C, and its swelling rate also has been slow, which ensure the stability as a kind of biomaterials, such as microcapsule and microspheres. And the time of native gelatin film achieving equilibrium swelling state is 9 minutes, and the time is 14 minutes for composite film, which means the oxidized chitin can delay the complete swelling rate. And the equilibrium swelling ratio of native gelatin film is larger than that of composite film. Therefore, the composite film will have a good prospects as a kind of potential biomedical.

In the present study, we investigated the effect of classic PDE4 inhibitor rolipram and novel PDE4 inhibitor ZL-n-91 on LPS-induced acute lung injury (ALI) in mice and its mechanism. ALI was induced in ICR mice by instilling intratracheally with LPS, and mice were divided into seven groups: control (Saline), LPS group, ZL-n-91 (3 microg, 10 microg, and 30 microg kg(-1), ip), Rolipram (1.0 mg kg(-1), ip) and dexamethasone (0.5 mg kg(-1), ip). After the 6h of instilling intratracheally with LPS in mice, total leukocyte number, neutrophil number and protein content in BALF increased rapidly, a large number of neutrophil infiltration around the pulmonary vessel and airway, the lung wet weight/dry weight (w/d)ratio raised significantly. MPO activity, TNF-alpha level and cAMP-PDE, PDE4 activity in lung homogenate raised significantly. P(a)O(2), P(a)CO(2) and PH value in peripheral arterial blood also changed obviously, P(a)O(2) and PH value dropped slightly and P(a)CO(2) increased significantly in LPS group. ZL-n-91 (3 microg, 10 microg, 30 microg kg(-1)) dose-dependently reduced the total leukocyte number, neutrophil number and total protein content in BALF, MPO activity, TNF-alpha level and cAMP-PDE, PDE4 activity in lung homogenate, but the effect of ZL-n-91 in pathological changes and lung wet w/d ratio is slight; Rol and Dex significantly reduced lung wet w/d ratio and improved pathological changes, neutrophil around the pulmonary vessel and airway significantly reduced, symptoms of lung edema relieved; The PH value, P(a)O(2) and P(a)CO(2) in ZL-n-91 high dosage group and Rol group had changes, but there was no significant difference compared with LPS group or saline group; After the administration, the righting reflex recovery time significantly shorten in every group of ZL-n-91. the righting reflex recovery time of Rol group was similar with ZL-n-91 30 microg kg(-1) group, while Dex group was similar with saline group. The present study confirms that the inhibitory effect of ZL-n-91(30 microg kg(-1)) on the inflammatory reactivity, including inhibition of inflammatory cell and protein exudation, MPO and PDE4 activity, improvement of the blood gas, those effects were equivalent with rolipram 1 mg kg(-1), and suggested that ZL-n-91 was stronger than rolipram in PDE4 inhibition. So we speculated that ZL-n-91 may have stronger therapeutic potential for treatment of inflammatory disease than rolipram, meantime have stronger nervous system effect than rolipram.

This study aims to investigate the protective role of crocetin, a natural antioxidant, against cytotoxicity produced by exposure to norepinephrine (NE) in primary cultured rat cardiac myocytes. Reactive oxygen species (ROS) and Ca(2+) in cells were evaluated by fluorescence microplate reader using 6-carboxy-2',7'-dichlorofluorescein and fluoro-3-acetoxymethyl ester, respectively. Lipid peroxidation was quantified using thiobarbituric acid-reactive substances. The activities of superoxide dismutase (SOD) and contents of glutathione (GSH) were detected by xanthine/xanthime oxidase-mediated ferricytochrome c reduction assay, and recycling effection of glutathione disulfide with GSH reductase and NADPH, respectively. The apoptotic cells were assayed by fluorescein diacetate (FDA)-ethidium bromide (EB) two-staining method. Intracellular accumulation of ROS, Ca(2+), and products of lipid peroxidation resulting from NE were significantly reduced by crocetin. Preincubation of primary cultured rat cardiac myocytes with crocetin remarkably prevented the decrease in SOD activity and quantities of GSH induced by NE. The percentage of NE-induced apoptosis in the cells was decreased by FDA-EB two-staining assay after pretreated with crocetin. The results showed that crocetin may ameliorate NE-induced injury in cardiac myocytes by enhanced SOD activity and increased quantities of GSH, decreased lipid peroxidation and Ca(2+) in cells, and apoptosis death ratio that may represent the cellular mechanisms for its cardioprotective role.

Here we first identified a novel pyridazinone derivative, compound 3711, as a nonnucleosidic hepatitis B virus (HBV) inhibitor in a cell model system. 3711 decreased extracellular HBV DNA levels by 50% (50% inhibitory concentration [IC 50 ]) at 1.5 ± 0.2 μM and intracellular DNA levels at 1.9 ± 0.1 μM, which demonstrated antiviral activity at levels far below those associated with toxicity. Both the 3TC/ETV dually resistant L180M/M204I mutant and the adefovir (ADV)-resistant A181T/N236T mutant were as susceptible to 3711 as wild-type HBV. 3711 treatment induced the formation of genome-free capsids, a portion of which migrated faster on 1.8% native agarose gel. The induced genome-free capsids sedimented more slowly in isopycnic CsCl gradient centrifugation without significant morphological changes. 3711 treatment decreased levels of HBV DNA contained in both secreted enveloped virion and naked virus particles in supernatant. 3711 could interfere with capsid formation of the core protein (Cp) assembly domain. A Cp V124W mutant, which strengthens capsid interdimer interactions, recapitulated the effect of 3711 on capsid assembly. Pyridazinone derivative 3711, a novel chemical entity and HBV inhibitor, may provide a new opportunity to combat chronic HBV infection.

During the hepatitis B virus (HBV) life cycle, nucleocapsid assembly is essential for HBV replication. Both RNA reverse transcription and DNA replication occur within the HBV nucleocapsid. HBV nucleocapsid is consisted of core protein (HBcAg), whose carboxy-terminal domain (CTD) contains an Arg-rich domain (ARD). The ARD of HBcAg does contribute to the encapsidation of pregenomic RNA (pgRNA). Previously, we reported a small-molecule, NZ-4, which dramatically reduced the HBV DNA level in an in vitro cell setting. Here, we explore the possible mechanisms by which NZ-4 inhibits HBV function. As an HBV inhibitor, NZ-4 leads to the formation of genome-free capsids, including a new population of capsid that runs faster on agarose gels. NZ-4's activity was dependent on the presence of the ARD I, containing at least one positively charged amino acid. NZ-4 might provide a new option for further development of HBV therapeutics for the treatment of chronic hepatitis B.

This paper indicated that inactivatedBordetella pertussis(iBp) can enhance the lung airway hyperreactivity of the rats sensitized and challenged with OVA. The mechanisms were involved in the upregulation of cAMP-PDE activity and PDE4A, PDE4D, and PDE3 gene expression in the lungs. But only PDE4 activity was different between the OVA and OVA+iBp groups, and PDE4D expression was significantly increased in iBp rats alone. So, our data suggested that cosensitization with OVA and iBp affects lung airway reactivity by modulating the lung cAMP-PDE activity and PDE4D gene expression.

To investigate the protective effects of Sapindus saponins in spontaneously hypertensive rats, and the possible cellular and molecular mechanisms. Thirty-two 16-week-old spontaneously hypertensive rats were randomly divided into four groups (8 in each group): model group (placebo), positive control group (27 mg/kg of Captopril Tablets), Sapindus saponins groups (27 mg/kg and 108 mg/kg, respectively). Another 8 healthy Wistar-Kyoto strain (WKY) rats were used as the normal group. The animals were treated for 8 weeks. Blood pressure of rats was determined by non-invasive blood pressure meter (BP-6). Furthermore, the contents of angiotensin II (Ang II) in plasma and myocardial tissue were determined by enzyme-linked immunosorbent assay (ELISA), the gene expression of receptor angiotensin type 1 (AT1R) in aorta was determined by quantitative realtime polymerase chain reaction (qRT-PCR). The protein expression of transforming growth factor-β1 (TGF-β1) and AT1R in heart was determined by immunohistochemical staining. The protein expression of p-phosphorylation of p38 mitogen-activated protein kinase (p-p38MAPK) was determined by Western blotting. The contents of interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF) in serum were determined by radioimmunoassay. And the histopathological and morphological changes of aorta and heart tissue samples were assessed semi-quantitatively by hematoxylin-eosin (HE) or Masson staining. Thirty minutes after single or continuous treatment, systolic blood pressure (SBP) was reduced significantly in Sapindus saponins groups. And the contents of AngII, IL-1, IL-6 and TNF-α in serum, the expression of AT1R mRNA, p-p38MAPK and TGF-β1 were significantly suppressed dose-dependently (P

OBJECTIVE To investigate the regulation on endothelial function of sapindus saponins in spontaneously hypertensive rats by studying the reactivity on different vasoconstrictor and dilator, and the content of the active substances. METHOD Forty 16-week-old spontaneously hypertensive rats were randomly divided into five groups, one with placebo as model group, one with captopril tablets (27 mg x kg(-1)) as positive control, one with low-dose sapindus saponins (27 mg x kg(-1)), one with medium-dose (54 mg x kg(-1)), one with high-dose (108 mg x kg(-1)). And another eight healthy Wistar-Kyoto strain (WKY) rats were used as the normal group. The animals were treated for eight weeks, and the indicators to be detected were as follows: (1) the response of thoracic aorta on different vasoconstrictors Ang II (1 x 10(-9) -1 x 10(-5) mol x L(-1)), PE (1 x 10(-8) 1 x 10(-4) mol x L(-1)), KCl (20 -120 mmol x L(-1)); (2) the endothelium-dependent or non-endothelium-dependent vasodilation response of thoracic aorta on Ach (1 x 10-(10)-1 x 10(-5) mol x L(-1)) or SNP (1 x 10(-8)-1 x 10(-3) mol x (L(-1); (3) the content of NO, 6-KPG1alpha, ET-1 and TXB2 in serum was determined by Elisa. RESULT In SHR model group, the response of thoracic aorta on Ang II, PE and KCl was increased, the endothelium-dependent vasodilation on Ach was reduced, but the effects on SNP was not obvious, the content of ET-1 and TXB2 was increased, and the content of NO and 6-KPG1alpha was reduced, Vs the normal control group, there were significant differences (P < 0.05 or P < 0.01); in the treatment groups, the response of thoracic aorta on Ang II, PE and KCl was reduced, the endothelium-dependent vasodilation of thoracic aorta on Ach was improved, the content of ET-1 and TXB2 was reduced, and the content of NO and 6-KPG1alpha was increased, Vs the SHR model group, there were significant differences (P < 0.05 or P < 0.01). CONCLUSION Our findings suggested that sapindus saponins protected the endothelial function in SHR, the mechanisms were relevant to the protection of endothelial function.

The present study was undertaken to investigate the protective effects of saponin on a hypertensive target organ (the kidney) in spontaneously hypertensive rats (SHRs) and also to explore the effect of saponin on the renin-angiotensin-aldosterone system (RAAS). A total of 24, 14-week-old SHRs were randomly divided into three groups; the first was administered low-dose saponin, the second with high-dose saponin and the third with a placebo as the control group. An additional eight healthy male Wistar rats were used as the normal group. The blood pressures (BPs) of the rats were determined using an animal BP-6 non-invasive blood pressure tester. Furthermore, the gene expression of TGFB1, collagen I and prorenin receptor (PRR) was determined by quantitative real time (qRT)-PCR. The histopathological and morphological features of the tissue samples were assessed semi-quantitatively. The content of saponin in the renal samples was lower in SHRs than in the normal healthy rats, but the plasma levels of saponin were similar. Mean arterial pressure (MAP) was reduced 5 days subsequent to saponin treatment by 36±3 and 51±4 mmHg in the low- and high-dose saponin groups, respectively. The anti-hypertensive effect of saponin was dose-related during the first 4 weeks of treatment. The gene expression of TGFB1 and collagen I in the renal samples was significantly suppressed in the low- and high-dose saponin groups compared with that in the control group. The gene expression of PRR was significantly and dose-dependently increased in the saponin-treated groups. These findings suggested that saponin reduced systemic BP and blocked the circulating and tissue RAAS.

A procedure for simultaneous identification and quantification of canrenone and its biotransformed product 11- α-hydroxy-canrenone by high-performance liquid chromatography with ultraviolet detector (HPLC-UVD) and mass spectrometry (LC-MS) methods was proposed. The optimal determination variables on the HPLC-UVD or LC-MS coupled with a ZORBAX Eclipse XDB-C18 column (150 mm × 4.6 mm, 5 μm) were set as follows: detection wavelength of 280 nm, mobile phase of water and methanol gradient elution, temperature for the chromatographic column of 30°C, flow rate of mobile phase of 0.8 mL/min, sample injection volume of 5 μL, and elution time of 40 min. The MS conditions were set as follows: the flow rate of sheath gas, aux gas, and sweep gas were kept at 35 arb, 5 arb, and 0 arb, respectively. The temperature of capillary was held at 300°C, and capillary voltage was set at 30.00 V. Tube lens were performed at 100.00 V. The proposed method was validated by linearity ( 𝑟 2 ≥ 0.9910), average recovery (94.93%, RSD1.21%), precision (RSD ≤ 1.31%), limit of detection, and limit of quantification (LOD 0.1~0.12 mg/L, LOQ 0.5~0.67 mg/L), which proved to be affordable for simultaneously determining canrenone and its bio-transformed product 11- α-hydroxy-canrenone.

Chronic obstructive pulmonary disease (COPD) is defined as a disease state characterized by poorly reversible airflow limitation induced by cigarette smoking and/or other noxious particle and gases. Phosphodiesterase (PDE) 4 inhibitors are known to elevated cAMP concentrations in inflammatory cells, leading to inhibition of inflammatory response, relaxation of smooth muscle in the airway, and modulation of sensory nerves in the lung as well. To investigate whether Zl-n-91, a new selective PDE4 inhibitor, could decrease inflammation and improve lung function in a COPD-like rat model, male Sprague-Dawley rats are used to challenge with lipopolysaccharide (LPS) and cigarette smoking (CS) exposure to induce COPD-like animal model. Administration of Zl-n-91 at different dosages results in decreases of inflammatory cell in bronchoalveolar lavage fluid (BALF) as compared with vehicle treatment. Zl-n-91 at 0.03, 0.3 or 3mg/kg not only dose-dependently inhibited PDE4 activity, but also decreased MMP-9 level in lungs and improved dynamic compliance (C(dyn)) as compared with vehicle treatment. Therefore, Zl-n-91 could inhibit inflammatory responses in rats after cigarette smoking exposure and LPS challenge, and it could be of some therapeutic potential as an alternative medicine in treatment of pulmonary diseases such as COPD.

Objectives. It is commonly held that Haemophilus influenzae pneumonia among children in Asia is mostly caused by serotypes other than b (Hib). If so, Hib conjugate vaccines would play little role in the prevention of pneumonia. In two prospective series of children hospitalized for pneumonia in China, the causative agents were searched for with a wide panel of microbiologic assays. Methods. In the university hospitals of Beijing and Hefei, 156 consecutive children 3 months of age and older with symptoms and signs of pneumonia were studied. Blood culture, chest radiograph, nasopharyngeal aspirate for viral antigen detection and paired sera for 20 microbiologic assays were taken. Severity was graded, and the course of illness was monitored uniformly. Results. In Beijing only likely contaminants grew from blood cultures, and in Hefei pathogens were identified in two cases. In combined series evidence for bacterial, mixed and viral etiology was obtained in 30, 7 and 21% of cases, respectively. The dominant bacteria were pneumococcus, Hib, Mycoplasma pneumoniae and Chlamydia pneumoniae, responsible for 13, 10, 8 and 8% of cases, respectively. Most patients were treated with extended spectrum antimicrobials such as piperacillin, cefotaxime or ceftriaxone, alone or in combination. One child died. Conclusions. As in most other series from other countries, the leading agent causing childhood pneumonia was pneumococcus but, in line with our previous experience from Beijing, the second most common agent detected was Hib. This observation suggests great potential for pneumococcal and Hib vaccinations in China. Because no evidence supported the need for routine use of extended spectrum antimicrobials, narrower spectrum agents would be safer for patients, would be cheaper for the community and would offer a way to address increasing resistance problems.

Background Little is known of the etiology of childhood acute lower respiratory infections in China, where the use of antimicrobials is indiscriminate. Trials to change such a policy require etiologic data, especially on the bacteria most relevant to these common diseases. Methods. One hundred consecutive infants and children from 3 months to 14 years of age with symptoms and signs compatible with acute lower respiratory infections were studied prospectively in the largest pediatric hospital in Beijing from February to May, 1997. Blood culture, thorax radiography and paired sera for 20 microbiologic assays were taken, and the course of illness was monitored uniformly. Disease severity was graded. Results. In 24 cases there was evidence only of bacterial etiology, and in 5 solely viral agents were found; 3 children probably had a mixed bacterial-viral infection. Surprisingly no pneumococcal infection was detected, Mycoplasma pneumoniae (n = 21), Haemophilus influenzae type b (n = 8) and Chlamydia pneumoniae (n = 7) being the dominant bacteria. All children recovered. Conclusions. Routine use of antimicrobials for these patients seems unjustified. Serologic evidence for the H. influenzae type b etiology is encouraging in terms of vaccination, but confirmatory studies are needed.