ABSTRACT
Importance: Epidural anesthesia is a primary choice for cesarean delivery, but supplemental analgesics are often required to relieve pain during uterine traction. Objective: To investigate the sedative and analgesic effects of intravenous esketamine administered before childbirth via cesarean delivery with the patient under epidural anesthesia. Design, Setting, and Participants: This multicenter, double-blind randomized clinical trial assessed 903 women 18 years or older who had full-term single pregnancy and were scheduled for elective cesarean delivery with epidural anesthesia in 5 medical centers in China from September 18, 2021, to September 20, 2022. Intervention: Patients were randomized to receive intravenous injection of 0.25 mg/kg of esketamine or placebo before incision. Main Outcomes and Measures: The coprimary outcomes included scores on the numeric rating scale of pain (an 11-point scale, with 0 indicating no pain and 10 indicating the worst pain; a difference of ≥1.65 points was clinically meaningful) and Ramsay Sedation Scale (a 6-point scale, with 1 indicating restlessness and 6 indicating deep sleep without response; a difference of ≥2 points was clinically meaningful) immediately after fetal delivery. Secondary outcomes included neonatal Apgar score assessed at 1 and 5 minutes after birth. Results: A total of 600 women (mean [SD] age, 30.7 [4.3] years) were enrolled and randomized; all were included in the intention-to-treat analysis. Immediately after fetal delivery, the score on the numeric rating scale of pain was lower with esketamine (median [IQR], 0 [0-1]) than with placebo (median [IQR], 0 [0-2]; median difference, 0; 95% CI, 0-0; P = .001), but the difference was not clinically important. The Ramsay Sedation Scale scores were higher (sedation deeper) with esketamine (median [IQR], 4 [3-4]) than with placebo (median [IQR], 2 [2-2]; median difference, 2; 95% CI, 2-2; P < .001). The neonatal Apgar scores did not differ between the 2 groups at 1 minute (median difference, 0; 95% CI, 0-0; P = .98) and at 5 minutes (median difference, 0; 95% CI, 0-0; P = .27). Transient neurologic or mental symptoms were more common in patients given esketamine (97.7% [293 of 300]) than in those given placebo (4.7% [14 of 300]; P < .001). Conclusions and Relevance: For women undergoing cesarean delivery under epidural anesthesia, a subanesthetic dose of esketamine administered before incision produced transient analgesia and sedation but did not induce significant neonatal depression. Mental symptoms and nystagmus were common but transient. Indications and the optimal dose of esketamine in this patient population need further clarification, but study should be limited to those who require supplemental analgesia. Trial Registration: ClinicalTrials.gov Identifier: NCT04548973.
Subject(s)
Analgesia, Epidural , Cesarean Section , Pregnancy , Infant, Newborn , Humans , Female , Adult , Cesarean Section/adverse effects , Pain Management , PainABSTRACT
OBJECTIVE: To investigate the regulatory effect of zyxin on the distribution of platelet cytoskeleton. METHODS: Platelets were isolated from zyxin-knockout (Zyx-/-) and wild type (WT) mice respectively and corresponding platelet cytoskeleton components were separated. The expressions of ß-actin, α-actinin, filamin A and myosin â ¡A in cytoskeleton components were detected by Western blot. Actin polymerization was induced by the actin polymerization inducer Jasplakinolide (Jas) in WT and Zyx-/- platelets. Also, the expressions of the cytoskeleton proteins in cytoskeleton components were detected by Western blot. WT and Zyx-/- platelets were allowed to spread on fibrinogen-coated surface. Platelet F-actin was labeled with Alexa Fluor 488-conjugated phalloidin and the fluorescent intensity was compared between WT and Zyx-/- platelets. RESULTS: After zyxin gene was knockout, the expressions of cytoskeleton proteins ß-actin, α-actinin, filamin A, and myosin â ¡ A in resting and Jas-induced platelets were significantly increased. In the platelet spreading on fibrinogen surface, F-actin was increased in Zyx-/- platelets as compared with that in WT platelets. CONCLUSION: Zyxin significantly regulates the distribution of platelet cytoskeleton, which plays an important role in maintaining platelet cytoskeleton homeostasis.
Subject(s)
Blood Platelets , Cytoskeleton , Actinin , Actins , Animals , Mice , ZyxinABSTRACT
OBJECTIVE: To investigate the inducing effect of PKA inhibitor H89 of different concentrations on platelet apoptosis and its mechanism. METHODS: Platelets were isolated from peripheral venous blood of healthy volunteers. Different concentrations gradient PKA inhibitor H89 were co-incubated with washing platelets, and the effects of PKA inhibitor H89 at different concentrations on platelet mitochondrial membrane potential, phosphatidylserine and reactive oxygen species(ROS) were determined by ELISA and flow cytometry. RESULTS: Different concentration of PKA inhibitor H89 could induce the depolarization of mitochondrial membrane potential and PS exposure of platelet. However, high concentration(100 µmol/L) PKA inhibitor H89 could induce the production of ROS in platelets, but medium and low concentrations did not induce the production of ROS in platelets. And several ROS inhibitors could inhibit the apoptosis induced by high concentration PKA inhibitor H89. CONCLUSION: High concentration H89 can induce platelet apoptosis, however the mechanism of platelet apoptosis caused by H89 of high concentration is different from H89 at medium and low concentrations.
Subject(s)
Blood Platelets , Intracellular Signaling Peptides and Proteins , Apoptosis , Humans , Membrane Potential, MitochondrialABSTRACT
OBJECTIVE: To investigate electrocardiographic (ECG) characteristics and radiofrequency catheter ablation (RFCA) efficacy for premature ventricular complexes (PVCs) and idiopathic ventricular tachycardias (IVTs) originating from ventricular septum areas adjacent to atrioventricular annulus (VS-AVA). METHODS: Among 1,505 consecutive PVCs/IVTs cases, 106 (7.04%) were confirmed as origin of VS-AVA guided by both fluoroscopy and three-dimensional mapping system during RFCA. Characteristics of surface 12-lead ECG were analyzed. RESULTS: The overall success rate for RFCA of PVCs/IVTs originating from VS-AVA was 82.08% (87/106), common ECG characteristics were: mainly positive R wave on lead I; dominant-positive R on aVL (91/106, 85.85%) for most, r (1/106, 0.94%) or qr (14/106, 13.21%) in few; QS or qs on aVR; and decreasing R wave amplitude and increasing S wave depth on II, III, and aVF from superior to inferior septum; and S wave on at least one inferior lead (generally III). Distinctive ECG features were: precordial transition zone before or after V2 for septum adjacent to mitral (MA, 19/19, 100.0%) or tricuspid (TA, 74/87,85.05%) annulus origin; initial r wave and rS on V1 for superior septum near TA (above His bundle) origin (9/10, 90.0%) with no initial r wave for most other origins; and QS on V1 for mid-inferior septum near TA origin (73/77, 94.81%) and QR (Qr, qR or qr) on V1 for septum near MA origin (17/19, 89.47%). CONCLUSION: Distinctive ECG characteristics of PVCs/IVTs originating from VS-AVA aid in origin localization guiding effective RFCA.
Subject(s)
Bundle of His/physiopathology , Catheter Ablation/methods , Electrocardiography/methods , Tachycardia, Ventricular/physiopathology , Ventricular Septum/physiopathology , Adolescent , Adult , Aged , Aged, 80 and over , Bundle of His/diagnostic imaging , Bundle of His/surgery , Child , Female , Follow-Up Studies , Heart Conduction System/diagnostic imaging , Heart Conduction System/physiopathology , Humans , Male , Middle Aged , Retrospective Studies , Tachycardia, Ventricular/diagnostic imaging , Tachycardia, Ventricular/surgery , Treatment Outcome , Ventricular Septum/diagnostic imaging , Ventricular Septum/surgery , Young AdultABSTRACT
BACKGROUND: Cervical cancer is a significant public health issue in Xinjiang China. In order to provide scientific basis for cervical cancer intervention in Xinjiang, women's knowledge of cervical cancer was investigated in this study. Besides, relations between Uyghur women's awareness and their age, educational background, yearly household were evaluated. METHODS: Questionnaire survey was conducted to 7100 Uyghur women from Karkax Hotan and Payzivat Kashgar during 2008 and 2009. Women aged 21 to 70 years, had sexual activity, no history of cervical lesion or cervical cancer were considered to be eligible to the study. Information include participants' socio-demographic background, personal data, awareness about Pap smear, about cervical cancer and HPV, sources of information acquisition was investigated. RESULTS: 65.1% of the 7100 respondents with primary education level, and 95.0% participants were farmers. Only 7.4% had undertaken Pap smears before, not aware of the importance of the test (97.4% of 7100) was the main reason for not performing Pap smears. 29.3% of total participants had heard about cervical cancer, and only 0.14% (10 out of 7100) had heard about HPV. Top three route of knowledge acquire were television advertises (39.1%), neighbors (21.0%) and health care providers (15.0%). Women younger than 40 years, with higher educational levels and higher income had better awareness of cervical cancer and more willing to accept regular Pap smears. CONCLUSIONS: Uyghur women in Xinjiang had poor knowledge of cervical cancer and HPV infection. Low awareness of women was associated with less household income and lower educational levels. TV shows and education from health care providers may increase women's participation in cervical cancer control and prevention.
Subject(s)
Ethnicity/psychology , Health Knowledge, Attitudes, Practice , Papanicolaou Test/psychology , Uterine Cervical Neoplasms/psychology , Vaginal Smears/psychology , Adult , Aged , China , Female , Humans , Middle Aged , Surveys and Questionnaires , Young AdultABSTRACT
The long noncoding RNA nuclear enrich abundant transcript 1 (NEAT1) has been identified to be carcinogenic in various cancers and elevated NEAT1 expression was tightly linked to tumorigenesis and progression. However, the mechanism has not been revealed in progression of thyroid cancer. Tumor xenograft mouse model was established and tumor size was evaluated. Arg1, NEAT1 and miR214 expression in CBMs, TAMs, BMDMs and RAW 264.7 cell lines were detected. TPC1 cells were subjected to siNEAT1 transfection in vitro for cell viability study. A direct target of miRNA214 (ßcatenin) was assessed, cell survival and invasion in TAMs were investigated. NEAT1, Arg1 was highly expressed and miRNA214 had lower expression in patients with thyroid cancer. NEAT1 knockout inhibited thyroid cancer cell survival, migration and invasion, along with reduced ßcatenin (a direct target of miRNA214) protein expression. Furthermore, NEAT1 significantly accelerated thyroid cancer cell growth and metastasis in vitro and increased tumor size in vivo. Upregulation of NEAT1 decreased the expression of miRNA214, presenting a reciprocal repression correlation. In conclusion, these results suggest that high expression of NEAT1 promoted the onset of thyroid carcinoma. In addition, NEAT1 promoted the malignant progression of thyroid cancer through regulating miRNA214 expression, which adds to our understanding of the molecular mechanisms in thyroid carcinoma.
Subject(s)
Arginase/genetics , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Thyroid Neoplasms/pathology , Animals , Cell Line, Tumor , Cell Proliferation , Cell Survival , Disease Progression , Gene Expression Regulation, Neoplastic , Humans , Mice , RAW 264.7 Cells , Thyroid Neoplasms/geneticsABSTRACT
BACKGROUND: The aim was to examine the association between 6 single nucleotide polymorphisms (SNPs) of peroxisome proliferator-activated receptors α (PPAR α) poly morphisms and C-reactive protein (CRP) level, as well as additional gene-gene interaction among the 6 SNPs. METHODS: A total of 1260 subjects (583 men, 677 women), with a mean age of 41.3 ± 14.6 years old, were selected. Six SNPs of PPAR α were selected for genotyping in the study including: rs135539, rs135551, rs135549, rs1800206, rs1800243 and rs4253623. Linear regression analysis was performed to verify the polymorphism association between SNP with CRP levels. Generalized MDR (GMDR) was employed to analysis the interaction among six SNPs. RESULTS: Linear regression results indicated a significant negative correlation between mutation of rs1800206 and CRP level. The carriers of the V allele (LV + VV) of rs1800206 were associated with a significant decreased level of CRP (regression coefficients was -0.533, standard error was 0.148 (P < 0.001)). However, the other 5 SNPs in PPAR α were not significantly associated with CRP level before or after covariate adjustment. GMDR model indicated that there was a significant two-locus model (P = 0.0107) involving rs1800206 and rs135539, indicating a potential gene-gene interaction between rs1800206 and rs135539. Overall, the two- locus models had a cross-validation consistency of 10 of 10, respectively, and had the testing accuracy of 55.9%, respectively. CONCLUSIONS: Our results support an important association between rs1800206 minor allele (V) of PPAR α and lower CRP level. The interaction analysis showed a combined effect between rs1800206 and rs135539 on the lower CRP level.
Subject(s)
C-Reactive Protein/analysis , Epistasis, Genetic , PPAR alpha/genetics , Polymorphism, Single Nucleotide , Adult , Alleles , Asian People/genetics , China , Cross-Sectional Studies , Female , Genotype , Humans , Linear Models , Male , Middle Aged , MutationABSTRACT
A major goal of aging research now is to find pharmacological manipulations in healthspan extension. Icariin is a flavonol isolated from medicinal herbal tonics. We have previously reported that icariin extended the healthspan of invertebrate models. Here, we showed that long-term treatment with icariin starting at 12months of age extended healthspan and mean lifespan in C57BL/6 mice. In all our assays associated with healthspan, such as behavioral tests and bone density analysis, we found that icariin boosted healthy features in mice. We also presented data indicating that such beneficial effects of icariin were due to at least two mechanisms: reduced oxidative stress indicated by the induction of antioxidant protein superoxide dismutase (SOD) activity and the decrease of oxidative marker malondialdehyde (MDA); maintained the genomic stability indicated by a reduction in DNA double-stranded breaks and down-regulation of DNA damage response genes. Our results indicated that icariin, a safe and widely used natural flavonol, extended healthspan and maintained genomic stability in a mammalian system.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Flavonoids/pharmacology , Longevity , Oxidative Stress/drug effects , Aging , Animals , Antioxidants/pharmacology , Down-Regulation/drug effects , Flavonols/pharmacology , Life Expectancy , Longevity/drug effects , Longevity/physiology , Male , Malondialdehyde/metabolism , Mice , Superoxide Dismutase/metabolism , Treatment OutcomeABSTRACT
Dyslipidemia increases the risks for atherosclerosis in part by impairing endothelial integrity. Endothelial progenitor cells (EPCs) are thought to contribute to endothelial recovery after arterial injury. Oxidized low-density lipoprotein (ox-LDL) can induce EPC dysfunction, but the underlying mechanism is not well understood. Human EPCs were cultured in endothelial growth medium supplemented with VEGF (10 ng/mL) and bFGF (10 ng/mL). The cells were treated with ox-LDL (50 µg/mL). EPC proliferation was assayed by using CCK8 kits. Expression and translocation of nuclear factor-kabba B (NF-κB) were evaluated. The level of reactive oxygen species (ROS) in cells was measured using H2DCF-DA as a fluorescence probe. The activity of NADPH oxidase activity was determined by colorimetric assay. Ox-LDL significantly decreased the proliferation, migration, and adhesion capacity of EPCs, while significantly increased ROS production and NADPH oxidase expression. Ox-LDL induced NF-κB P65 mRNA expression and translocation in EPCs. Thus ox-LDL can induce EPC dysfunction at least by increasing expression and translocation of NF-κB P65 and NADPH oxidase activity, which represents a new mechanism of lipidemia-induced vascular injury.
Subject(s)
Endothelial Cells/cytology , Endothelial Cells/metabolism , Lipoproteins, LDL/pharmacology , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , NF-kappa B/metabolism , Cells, Cultured , Endothelial Cells/drug effects , Female , Fetal Blood/cytology , Humans , Mesenchymal Stem Cells/drug effects , Oxidative Stress/drug effects , Oxidative Stress/physiologyABSTRACT
OBJECTIVE: To study the distribution of HLA-DRB1 allele polymorphism in Uyghur women with family history of cervical cancer, and provide theoretical evidence for detection and follow-up of high risk persons for cervical cancer by detection of HLA-DRB1 allele polymorphism. METHODS: The HLA-DRB1 13 alleles were detected in 1000 Uyghur women, all from Hotan Moyu county Karsay village by using polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) assay. RESULTS: The frequencies of HLA-DRB1*15 in women with family history of cervical cancer (17.3%), mother (18.0%) and other relatives except mother (17.0%) who had suffered from cervical cancer were significantly higher than that in the control group (9.7%, all P < 0.05). The frequencies of HLA-DRB1*04 in women with family history (16.8%) and other relatives except mother (20.7%) were significantly higher than that in the control group (12.7%, all P < 0.05). The frequencies of HLA-DRB1*03 in women with family history (2.6%) and other relatives except mother (1.1%) were significantly lower than that in the control group (6.3%, all P < 0.01). The frequencies of HLA-DRB1*12 in women with family history of cervical cancer (2.3%) and mother suffered from cervical cancer (1.5%) were significantly lower than that in the control group (5.7%, all P < 0.05). The frequencies of HLA-DRB1*14 in women with family history of cervical cancer (5.4%) and mother who suffered from cervical cancer (3.0%) were significantly lower than that in the control group (8.4%, all P < 0.05). CONCLUSIONS: There are similarity and difference in distribution of HLA-DRB1 allele polymorphisms between the Uyghur women with family history of cervical cancer from Hotan Moyu county and those from southern Xingjiang area. In general, the distribution of HLA-DRB1 allele polymorphism in women with family history of cervical cancer is similar to that reported in abroad. The results of this study support the role of susceptible and protective HLA gene detection in screening high risk persons for this cancer among Uyghur women from cervical cancer high risk areas in Xinjiang.
Subject(s)
Alleles , HLA-DRB1 Chains/genetics , Polymorphism, Genetic , Uterine Cervical Neoplasms/genetics , Asian People/ethnology , Asian People/genetics , China/ethnology , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Uterine Cervical Neoplasms/immunologyABSTRACT
OBJECTIVE: To study the distribution of human papilloma virus (HPV) subtypes in Uyghur people from the high risk region of cervical cancer in Xinjiang. METHODS: 21 subtypes of HPV from 400 cases of men's swabs of penile and 400 cases of women's cervix swabs were detected, using flow-through hybridization and gene chip technology. RESULTS: (1) The positive rate of HPV among the 400 women cases was 14.25%, with HPV16 the most common type. In women whose HPV was positive, the positive rate of HPV16 was 66.67%. The ranking of frequencies on the HPV subtypes in women were:HPV16, 58, 39, 18, 33, 52, 43, 66, CP8304, HPV6 and 11. (2) Among the 400 male cases, the positive rate of HPV was 8.00%, with HPV16 the most common type. In men whose HPV was positive, the rate of HPV16 was 44.44%. The ranking of HPV subtypes in men were HPV16, 43, 33, 39, 6 (HPV39 and 6 are equivalent) and 53. (3) Both wives and husbands were infected by different subtypes of HPV, the positive rate was relatively low among men whose wife's HPV were positive. However, the HPV positive rate was relatively low among women whose husband's HPV were positive. The concordance infection rate of women and men were 7.02% and the concordance infection rate of men and women were 9.38%. CONCLUSION: The HPV positive rates were relatively low in both men and women living in the region with high risk of cervical cancer in Xinjiang. However, the positive rate of high risk types HPV and HPV16 in both men and women were relatively high. Uyghur men seemed to have played a certain role related to the carcinogenesis of cervical cancer. HPV16 was the main type in both men and women in Xinjiang.
Subject(s)
Papillomaviridae/classification , Uterine Cervical Dysplasia/virology , Uterine Cervical Neoplasms/virology , Adult , Aged , Cervix Uteri/virology , China/epidemiology , Female , Humans , Male , Middle Aged , Papillomaviridae/isolation & purification , Papillomavirus Infections/ethnology , Surveys and Questionnaires , Uterine Cervical Neoplasms/ethnology , Young Adult , Uterine Cervical Dysplasia/ethnologyABSTRACT
Compounds that delay aging might also postpone age-related diseases and extend healthspan in humans. Icariin is a flavonol extracted from several plant species of the Epimedium family. The icariin and its metabolic derivatives have been shown to exert wide protective effects in age-related diseases. However, whether icariin and its derivatives have the potency of delaying aging remains unclear. Here, we report that icariin and its derivative icariside II extend C. elegans lifespan. Using HPLC, we found high level of icariside II in the animals treated with icariin, suggesting icariside II is the bioactive form in vivo of icariin. Icariside II also increased the thermo and oxidative stress tolerance, slowed locomotion decline in late adulthood and delayed the onset of paralysis mediated by polyQ and Aß(1-42) proteotoxicity. The lifespan extension effect of icariside II is dependent on the insulin/IGF-1 signaling (IIS) since the daf-16(mu86) and daf-2(e1370) failed to show any lifespan extension upon icariside II treatment. Consistently, icariside II treatment upregulates the expression of DAF-16 targets in the wild-type. Moreover, our data suggests that the heat shock transcription factor HSF-1 has a role in icariside II-dependent lifespan extension further implicating the IIS pathway. In conclusion, we demonstrate a novel natural compound, icariside II as the bioactive form of icariin, extends the healthspan via IIS pathway in C. elegans.
Subject(s)
Caenorhabditis elegans/metabolism , Flavonoids/pharmacology , Insulin-Like Growth Factor I/metabolism , Insulin/metabolism , Longevity , Animals , Caenorhabditis elegans Proteins/metabolismABSTRACT
OBJECTIVE: To investigate the association between HPV infection and HLA-DQB1 alleles polymorphism in the cervical carcinogenesis in Uyghur women in southern Xinjiang. METHODS: Twenty-one subtypes of HPV and the 5 alleles of HLA-DQB1 were detected from cervical tissues of 190 cervical cancer cases and 190 normal subjects by flow-through hybridization and gene chip (HybriMax) assay and polymerase chain reaction sequence-specific oligonucleotide technique (PCR-SSO). RESULTS: (1) The positive rate of HPV in cervical cancer and control groups were 70.0% and 8.9%, respectively. HPV16 was the most common type in HPV positive cervical cancer patients with a rate of 64.7%, followed by HPV18 (2.6%), HPV68 (2.1%), HPV45 (1.6%), HPV58 (1.6%), HPV39 (1.6%), HPV31 (1.1%), HPV56 (1.1%), HPV59 (0.5%), HPV53 (0.5%) and HPV6 (0.5%), respectively. The positive rates of HPV and HPV16 in the cervical cancer group were significantly higher than that in the control group. (2) The frequency of HLA-DQB1*03 was significantly lower than that in the control group (OR = 0.683, 95%CI = 0.505 - 0.923). The frequency of other HLA alleles had no significant differences between the cervical cancer group and the control group. (3) In the cervical cancer group, the frequency of HLA-DQB1*06 in both HPV positive and HPV16 positive cases were significantly higher than that in both the HPV and HPV16 negative cases. CONCLUSION: HPV16 is the most common type in both the cervical cancer and control groups. It appears that HLA-DQB1*03 may be a protective gene in the cervical carcinogenesis in southern Xinjiang Uyghur women, and the HLA-DQB1*06 is a susceptibility gene to HPV/HPV16 infection in Uyghur women. The study of HLA alleles in the cervical carcinogenesis in Uyghur women may play an important role in the intervention research of cervical cancer.
Subject(s)
HLA-DQ Antigens/genetics , Papillomaviridae/isolation & purification , Papillomavirus Infections/genetics , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/virology , Adult , Aged , Alleles , China/ethnology , Ethnicity/genetics , Female , Gene Frequency , Genetic Predisposition to Disease , HLA-DQ beta-Chains , Human papillomavirus 16/isolation & purification , Humans , Middle Aged , Polymorphism, Genetic , Uterine Cervical Neoplasms/immunology , Young AdultABSTRACT
OBJECTIVE: To study the optimal combined ratio of baicalin, icariin and Astragalus saponin I from a Chinese herbal compound Biminne. METHODS: Firstly, a mouse model of allergic rhinitis was established by intraperitoneal injection of ovalbumin (OVA) and aluminum hydroxide gel suspension, and the effective dose range of baicalin, icariin and Astragalus saponin I was detected by 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt method. Secondly, 10 groups of combinations of baicalin, icariin and Astragalus saponin I assembled by U(10)(10(8)) form were employed to determine the optimal combination by means of analyzing of the inhibitory effect on the splenocyte proliferation. Finally, the effects of each effective ingredient and the optimal combination were compared by observing the splenocyte proliferation, the contents of interleukin-4 (IL-4), IL-5, interferon-gamma (IFN-gamma) in supernatant of the splenocyte cultures and the ratio of IL-4 to IFN-gamma in order to verify the result. RESULTS: Baicalin or icariin at concentrations ranging from 2 to 10 micromol/L, and Astragalus saponin I from 1 to 10 micromol/L effectively suppressed the splenocyte proliferation. When the proportion of baicalin, icariin and Astragalus saponin I was 1:2.14:2.65, the inhibitory effect was most remarkable. Further research confirmed the rationality of the optimal combination. CONCLUSION: An optimal combination of the major effective ingredients from Chinese herbal compound Biminne most effectively suppresses the proliferation of splenocytes from sensitized mice and regulates the cytokine secreting.
Subject(s)
Astragalus Plant/chemistry , Drugs, Chinese Herbal/administration & dosage , Flavonoids/administration & dosage , Animals , Cell Line , Cell Proliferation/drug effects , Cytokines/metabolism , Disease Models, Animal , Drug Combinations , Drug Design , Drug Incompatibility , Male , Mice , Mice, Inbred BALB C , Rhinitis/immunology , Spleen/cytology , Spleen/immunologyABSTRACT
OBJECTIVE: To investigate the effects of Biminne, a traditional Chinese herbal formula, in regulating the endocrine-immune function in mice with airway allergy. METHODS: Forty BALB/c mice were randomly divided into four groups: control group, untreated group, Biminne group, and dexamethasone (Dex) group. The murine model of airway allergy was established by intraperitoneal injection sensitization and intranasal challenge with ovalbumin (OVA). On day 28, the mice were sacrificed and the sera were collected. The lung tissue of mice was removed for haematoxylin-eosin staining and the pathological changes were observed. The spleen cells of mice were isolated and the ratio of Th2/Th1 was determined by flow cytometry. The isolated spleen cells were also cultured in 24-well plates in the presence of concanavalin A and the supernatants were collected after 72-hour culture. Levels of interleukin-4 (IL-4), IL-5 and interferon-gamma (IFN-gamma) in the supernatants and the corticosterone level in sera were analyzed by enzyme-linked immunosorbent assay. RESULTS: Biminne significantly relieved the inflammatory reaction in the lung tissue of airway allergic mice. Compared with the control group, the Th2 cells in the untreated group increased, while the IFN-gamma level decreased and the ratio of Th2/Th1 increased significantly, showing a Th2 response priority. Biminne treatment could down-regulate the Th2 cells and their cytokines IL-4 and IL-5, and up-regulate the Th1 cells and their cytokine IFN-gamma. So the ratio of Th2/Th1 decreased significantly, shifting to the control level. In addition, Biminne also inhibited the reduction of the serum corticosterone of sensitized mice. CONCLUSION: The Chinese herbal formula Biminne can reverse the functional disorder of the endocrine-immune system, which may explain its therapeutic effects on airway allergic disease.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Hypersensitivity/metabolism , Th1 Cells/drug effects , Th2 Cells/drug effects , Animals , Drugs, Chinese Herbal/therapeutic use , Hypersensitivity/drug therapy , Hypersensitivity/immunology , Inflammation , Interferon-gamma/metabolism , Interleukin-4/metabolism , Interleukin-5/metabolism , Lung/pathology , Mice , Mice, Inbred BALB C , Phytotherapy , Th1 Cells/metabolism , Th2 Cells/metabolismSubject(s)
Neurofibroma , Pharyngeal Neoplasms , Humans , Male , Middle Aged , Neurofibroma/pathology , Pharyngeal Neoplasms/pathologyABSTRACT
OBJECTIVE: To investigate the effect and mechanism of Biminne, a Chinese herbal compound preparation, for treatment of allergic rhinitis (AR). METHODS: AR model of mouse was induced by intraperitoneal injection of ovalbumin (OVA), and the changes in behavior, proliferative activity of splenic lymphocyte, serum levels of total IgE and OVA specific IgE were observed. RESULTS: Biminne showed effects in reducing the frequency of sneezing and nasal rubbing, inhibiting the proliferation of splenic lymphocyte stimulated by phyto-hemagglutinin (PHA) and OVA, and lowering the levels of serum total IgE and OVA specific IgE. CONCLUSION: Biminne could inhibit the proliferation of splenic lymphocyte and reduce serum level of IgE in mice with AR.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Rhinitis, Allergic, Perennial/drug therapy , Animals , Cell Proliferation , Immunoglobulin E/blood , Lymphocytes/drug effects , Lymphocytes/immunology , Lymphocytes/pathology , Male , Mice , Mice, Inbred BALB C , Ovalbumin , Phytotherapy , Random Allocation , Rhinitis, Allergic, Perennial/chemically induced , Rhinitis, Allergic, Perennial/immunologyABSTRACT
OBJECTIVE: To investigate the haemodynamic and respiratory changes following intravenous administration with midazolam, pavulon or both of them in the patients having incoordination between spontaneous breathing and mechanical ventilation. METHODS: Thirty patients having incoordination between spontaneous breathing and mechanical ventilation were randomly assigned to receiving intravenous injection of pavulon (group 1), midazolam (group 3), and both (group 2) respectively with 10 cases in each group. The degree of coordination between spontaneous breathing and mechanical ventilation, blood pressure (BP), heart rate (HR), respiration frequency (RF), oxygen saturation of pulse (SpO(2)) were observed before the medication and at 5, 15, 30 and 60 minutes following the administration of drugs in all the patients. RESULTS: Incoordination between spontaneous breathing and mechanical ventilation, fast RF, decreased SpO(2) were observed before the drug in all patients. Improvement of respiratory was significant in group 2. Patients in group 2 were in excellent coordination between spontaneous breathing and mechanical ventilation, reaching 100% within 30 minutes after administration, and lasting longer. The haemodynamics maintained stable and a significant improvement in respiration and SpO(2) were found. BP and HR were elevated significantly, and RF and hypoxemia were improved, and the degree of coordination between spontaneous breathing and mechanical ventilation reached 100% 5 minutes after the drug, but with shorter duration in group 1. There were no obvious changes in BP, HR, RF and hypoxemia, and the degree of coordination between spontaneous breathing and mechanical ventilation was lowest in group 3. CONCLUSION: The combined use of midazolam and pavulon has little influence on circulation, and it also can maintain the coordination between spontaneous breathing and mechanical ventilation. It is suggested that the combined use of midazolam and pavulon is an optimal way to improve the ventilatory function in mechanical ventilation.