Anti RS virus drugs

Palivizumab is one of the monoclonal antibodies for RS virus(RSV), and has been widely used to preterm infants, infants with bronchopulmonary dysplasia, and infants with congenital heart disease. Palivizumab can reduce admission rate and length of hospital stay due to lower respiratory tract infection by RSV. Palivizumab can also reduce the rate of later recurrent wheezing. Motavizumab, the 2nd generation monoclonal antibody, has 18-fold greater neutralizing capacity to RSV. Clinical trials of motavizumab finished, however, motavizumab has not been granted because of skin complication. In anti RSV drugs, ribavirin administration is not recommended because the effect is unclear. Clinical trials of some new anti RSV drugs and two live attenuated intranasal vaccines are underway.     

Vitritis and retinal vasculitis caused by pseudorabies virus

Pseudorabies virus (PRV) is a herpesvirus of swine. PRV is also called suid herpesvirus 1 and is a member of the Alphaherpesvirinae subfamily within the family Herpesviridae. The number of PRV cases worldwide is small, but in susceptible individuals, infection with this virus has a poor prognosis. Therefore, it is urgent to improve our understanding of this disease in clinical practice to avoid misdiagnosis and to identify optimal treatments. We report a patient with PRV infection who was admitted to hospital with viral encephalitis and subsequently developed intraocular infection. Because to the lack of relevant clinical experience in the treatment of this disease, we carried out experimental treatment with good therapeutic effect. This case provides a basis for clinical diagnosis and treatment of patients with PRV.     

Morphogenesis of three pseudorabies virus strains in porcine nasal mucosa.

After intranasal inoculation of pseudorabies virus in 10-week-old pigs, the morphogenesis of three pseudorabies virus strains was studied in nasal mucosa. Virulent NIA-3 virus rapidly invaded the lamina propria of the nasal mucosa. NIA-3 nucleocapsids were enveloped at the nuclear membrane. Invasion of the lamina propria was delayed after intermediate virulent 2.4N3A virus infection or absent after nonvirulent Bartha virus infection. 2.4N3A virus was mainly enveloped by membranes of the smooth endoplasmic reticulum. Bartha virus replication was delayed for at least 24 h as compared with NIA-3 virus, and Bartha virus was also enveloped by membranes of the smooth endoplasmic reticulum. The virulence of 2.4N3A and Bartha virus may be diminished because of altered envelopment and delayed viral replication and release.     

核黄素联合紫外线A照射对血浆中伪狂犬病毒的灭活效果

目的考察核黄素联合紫外线A对血浆中伪狂犬病毒的灭活效果。方法以伪狂犬病毒为模拟病毒,以Vero细胞为培养细胞,用病毒感染细胞,制备病毒增殖液;分别采用5、10、15及20J/cm2联合核黄素处理血浆,观察处理前后血浆病毒灭活的效果,筛选灭活病毒合适的紫外线剂量;将含有伪狂犬病毒血浆的样本分为实验组:采用上述筛选的紫外线强度照射联合核黄素处理;对照组1:单独采用紫外线A照射;对照组2:单独采用核黄素处理;阴性对照组:未采用紫外线照射和核黄素处理;分别在实验前后采用96孔细胞病变法,对照细胞病变效应,根据Reed-Muench公式计算病毒滴度。结果采用不同强度的紫外线联合核黄素处理血浆,紫外线强度为15及20J/cm2的灭活血浆病毒的效果明显,处理后病毒滴度分别下降4.55和4.39logs;实验组和对照组1病毒滴度分别下降4.55和4.28logs,有统计学意义(P<0.05);对照组2病毒滴度降低1.93logs,没有病毒灭活效果。结论核黄素联合紫外线可灭活血浆中伪狂犬病毒,单独紫外线照射也具有灭活血浆伪狂犬病毒的效果;而仅单独采用核黄素处理而未联合紫外线照射,对血浆中伪狂犬病毒灭活效果不明显。     

Attachment and penetration properties of bovine herpesvirus 1 recombinants expressing pseudorabies virus glycoproteins gC and gB

OBJECTIVE: Bovine herpesvirus 1 (BHV-1) has a relatively narrow host cell range in vitro and in vivo when compared to pseudorabies virus (PrV). The aim of this study was to elucidate whether homologous glycoproteins gC and gB from PrV can function in a heterologous BHV-1 background and whether the expression of these PrV glycoproteins influences the in vitro host cell specificity of BHV-1. METHODS: We constructed BHV-1 recombinants in which PrV gC and gB were expressed either individually or in combination, and examined their attachment and penetration properties in permissive Madin-Darby bovine kidney (MDBK), semipermissive hamster lung (HmLu-1) and nonpermissive murine embryo fibroblast (A31) cells. RESULTS: Two BHV-1 recombinants which expressed PrV gC exhibited remarkable competence in virus attachment to cells. The expression of PrV gB improved the virus attachment only a little but penetration, especially into HmLu-1 and A31 cells, was enhanced. CONCLUSIONS: These results indicate that PrV gC and gB can function in a BHV-1 environment and facilitate virus attachment and penetration by BHV-1.     

Anti-inflammatory activity of the aqueous extract of ficus deltoidea

Ficus deltoidea (Family Moraceae) leaves have been used traditionally by the Malays to treat ailments such as wounds, sores, and rheumatism. The aim of the present study was to determine the anti-inflammatory activity of the aqueous extract of F. deltoidea leaf (FDA) using acute and chronic inflammatory models. FDA, in the doses of 30, 100, and 300 mg/kg, was administered intraperitoneally in rats (n = 6) before the animals were subjected to the carrageenan-induced paw edema test, cotton pellet-induced granuloma test, and formalin test. The first two tests represent acute and chronic models of inflammation, respectively. The first and second phases of the formalin test represent neurogenic pain and inflammatory-mediated pain, respectively; thus, only the second phase was measured in the present study. Results showed that FDA exerted significant (p < .05) anti-inflammatory activity in all assays, with dose-response effects seen in the paw edema and formalin tests. In conclusion, the leaf of F. deltoidea possesses anti-inflammatory activity against acute and chronic inflammatory responses and against pain-associated inflammatory response. These findings justify the traditional uses of F. deltoidea leaves for treatment of inflammatory-mediated ailments.     

Combined effect of acyclovir and amphotericin B on the replication of pseudorabies virus in BHK-21 cells

Acyclovir, known as an antiherpetic agent, showed an inhibitory effect on the propagation of pseudorabies virus in BHK-21 cells. The antiviral effect of acyclovir was observed by plaque reduction, as well as by the inhibition of the virus-stimulated uptake of thymidine by BHK-21 cells. Amphotericin B potentiated the antiviral activity of acyclovir. The optimal concentrations of polyene antibiotic expressing the potentiating effect were lower than required for the induction of K+ leakage from the cells. There was no evident amphotericin B-induced stimulation of thymidine incorporation into infected BHK-21 cells. The model presented may be useful to study the potentiation phenomenon of polyene macrolide antibiotics.     

Distribution of sequences homologous to the DNA of herpes simplex virus, types 1 and 2, in the genome of pseudorabies virus

The distribution of related sequences between the genomes of pseudorabies virus (PRV) and herpes simplex virus, types 1 (HSV-1) and 2 (HSV-2), was determined. Approximately 7% of the sequences in PRV are shared by HSV-1 and HSV-2 DNAs. By means of the Southern blot technique, it was found that the homologous sequences are not sequestered in one region but are distributed throughout the PRV genome. HSV-1 and HSV-2 have the greatest homology with the long unique region of PRV DNA and the least with the inverted repeat regions of the molecule. HSV-1 DNA also has few sequences homologous to the short unique region of the PRV genome; HSV-2 DNA hybridizes well to this region. There was no homology of HSV-1 or HSV-2 DNAs with the extreme ends of the inverted repeat regions of PRV DNA.     

桑叶提取物对酪氨酸酶活性的抑制作用

目的:研究桑叶提取物对酪氨酸酶活性的抑制作用,为预防和治疗色素沉着疾病提供实验依据。方法:实验采用桑叶、酪氨酸酶、L-酪氨酸、曲酸,测定不同浓度曲酸对酪氨酸酶活性的抑制作用,以抑制率(抑制率=1-酪氨酸酶活性%)结果选择阳性对照组,测定不同浓度的桑叶提取物对酪氨酸酶活性的抑制作用,并以桑叶提取物浓度为自变量,以桑叶提取物对酪氨酸酶活性抑制率为应变量,建立回归方程,确定桑叶提取物浓度与其对酪氨酸酶活性抑制率之间的相关关系。结果:13,14,15mg/L的曲酸对酪氨酸酶活性的抑制率分别为24.7%,71.89%,85.74%,酪氨酸酶活性率为50%时曲酸质量浓度为13.65mg/L;2.3,4.7,7,9.3,11.7g/L的桑叶提取物对酪氨酸酶活性的抑制率分别为24.49%,38.22%,51.95%,74.83%,79.41%,酪氨酸酶活性率为50%时桑叶提取物质量浓度为6.4g/L。桑叶提取物浓度与其对酪氨酸酶活性抑制率呈正相关(r=0.9855,P<0.05)。结论:桑叶提取物对酪氨酸酶活性起到了与曲酸相似的抑制作用。     

Antitumor activity of hot-water extract from delipidated BCG.

The antitumor activity of hot-water extract of delipidated BCG was investigated in mice inoculated with Sarcoma-180 cells and Ehrlich carcinoma cells, respectively. The hot-water extract was found to be effective when administered after and ineffective when administered before the inoculation of tumor cells. When this extract was given with anticancer drugs, such as Mitomycin C and cyclophosphamide, a combined effect was obtained in the treatment of Sarcoma-180 and of Ehrlich carcinoma.     

Antidepressant activity of an aqueous extract from okra seeds

Faced with the increasing incidence of major depression disorder (MDD) and the unsatisfactory effect of current drugs, there has been growing attention on the relation between dietary supplements and MDD prevention. In this research, the antidepressant activity of okra seed extract (OSE) was evaluated with behavioral tests including an open field test, tail suspension test (TST), forced-swimming test (FST) and novelty suppressed feeding test (NSFT) for sub-chronic treatment and chronic sleep-interruption (CSI) animal models. The chemical constituents of OSE were identified by using UPLC-DAD/Q-TOF MS. To investigate the mechanism, the prefrontal cortex and hippocampus were collected to determine neurotransmitters, total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA). Blood serum was prepared for the determination of corticosterone (CORT) and adrenocorticotropic hormone (ACTH). Results demonstrated that OSE possessed an antidepressant effect in both sub-chronic treatment and CSI animal models through suppressing the hyperactivation of the hypothalamic–pituitary–adrenal (HPA) axis, alleviating oxidative stress and regulating neurotransmitter levels in the hippocampus and frontal cortex. Besides, chemical analysis based on the UPLC-DAD/ESI-Q-TOF MS approach showed that OSE mainly contained catechin and quercetin derivatives. The present study provided a scientific basis for developing okra seeds to be a dietary supplement for MDD prevention.

Faced with the increasing incidence of major depression disorder (MDD) and the unsatisfactory effect of current drugs, there has been growing attention on the relation between dietary supplements and MDD prevention.     

Construction and immunogenicity of a gE/gI/TK-deleted PRV based on porcine pseudorabies virus variant

Pseudorabies (PR) caused by re-emerging pseudorabies virus (PRV) variant has outbroken among PRV vaccine-immunized swine herds on many Chinese pig farms, with severe socioeconomic consequences since late 2011. Here, a gE/gI/TK-deleted recombinant virus (rPRV NY-gE⁻/gI⁻/TK⁻) was constructed based on PRV NY strain from 2012 through homologous DNA recombination and gene-editing technology termed clustered regularly interspaced palindromic repeats (CRISPR)/associated (Cas9) system. The rPRV NY-gE⁻/gI⁻/TK⁻ strain showed similar growth kinetics to the parental PRV NY strain in vitro, and was safe for mice. Sixty mice were injected subcutaneously (s.c.) twice with 10^6.0 TCID₅₀ of rPRV NY-gE⁻/gI⁻/TK⁻ and DMEM, respectively, with two-week interval. The levels of PRV gB antibodies and neutralizing antibodies against PRV NY in mice immunized with rPRV NY-gE⁻/gI⁻/TK⁻ were higher than those in the DMEM control group. The number of T lymphocyte subclasses CD3⁺, CD4⁺ and CD8⁺ in rPRV NY-gE⁻/gI⁻/TK⁻-immunized mice was higher than that in DMEM-injected mice. After challenge with 10^6.0 TCID₅₀ PRV NY at 42 dpi, all rPRV NY-gE⁻/gI⁻/TK⁻-immunized mice survived without exhibiting any pathological lesions in different tissues and intranuclear eosinophilic inclusions of the brain, and the viral genomic copy numbers in various organs of mice were obviously lower than DMEM group. These results showed the rPRV NY-gE⁻/gI⁻/TK⁻ could be a promising next-generation vaccine to control now epidemic PR in China.     

Development of a semiquantitative PCR assay using internal standard and colorimetric detection on microwell plate for pseudorabies virus

We have developed a semiquantitative PCR assay on microtitre plates for quantitation of pseudorabies virus (PRV). The test is based on co-amplification with an internal control (IC) of the target viral DNA, followed by hybridization of the biotin-amplified products on a capture probe covalently immobilized to a Covalink-NH MicroWells plate and then visualization with colorimetric enzymatic reactions. PCR was performed in the presence of uracil-N-glycolsylase (UNG) with dUTP instead of dTTP to prevent false positive results due to carry-over contamination. Our colorimetric test had a 3·5 log dynamic range with a detection level of 30 DNA copies per PCR reaction. A standard curve for quantitation of pseudorabies virus was established from co-amplification of 10 to 10⁵PRV molecules with 1000 IC molecules. Ratios of viral optical density/IC optical density were plotted against the number of PRV DNA target molecules in the PCR amplification. Integration of 96-well formats and automation using robots at different steps of the test ensured a good repeatability. Calibration of the quantitative test using samples from experimentally-infected pigs is in progress.     

Anti-RNA virus activity of polyoxometalates.

The anti-RNA virus activity of polyoxometalates (POM) is reviewed, with a special emphasis on the anti-respiratory virus activities. There are many causative agents of acute viral respiratory infections; and it is rather difficult to identify the relevant agent in a given case by rapid clinical means. During acute progress of infection before the definitive diagnosis is obtained physicians need to prescribe certain broad spectrum anti-viral drugs. A titanium containing polyoxotungstate, PM-523 exhibited potent anti-influenza virus (FluV) A and anti-respiratory syncytial virus (RSV) activities in vitro. Therapeutic effect of FluV A infected mice with aerosol inhalation of PM-523 was proven. A vanadium substituted polyoxotungstate, PM-1001 has antiviral activity against FluV A, RSV, parainfluenza virus (PfluV) type 2, Dengue fiver virus, HIV-1 and SARS coronavirus in vitro. Thus, POMs have been proven to be broad spectrum and non-toxic anti-RNA virus agents in both in vitro and in vivo experiments and are promising candidates for first-line therapeutics in acute respiratory diseases.