ABSTRACT
Objective: To evaluate the effects of language awakening nursing and thermal insulation nursing on anesthesia in elderly patients undergoing spinal fracture surgery. Methods: Randomized control method was used in this study, 200 elderly patients who underwent spinal fracture surgery under general anesthesia between January and December 2022. Among the patients, 100 cases were selected as the observation group, and the other 100 cases were included in the control group by the random number table method. The control group was treated with thermal insulation nursing, and the observation group was given language arousal nursing (a type of care that helps patients regain consciousness after surgery or anesthesia) combined with thermal insulation nursing (A nursing method for maintaining a patient's body temperature in a medical setting). Results: After the intervention, the observation group showed shorter extubation time, awaking time, eye-opening time, and respiratory recovery time compared to the control group (P < .05). Systolic, diastolic, and MAP decreased in both groups after the intervention, with the observation group showing lower values (P < .05). Heart rate at 5 and 10 minutes after extubation decreased in both groups, with the observation group having a lower heart rate than the control group (P < .05). There were no significant differences in SPO2 between the groups after intervention (P > .05). The observation group reported milder pain and a lower incidence of anesthesia-related adverse reactions (P < .05). These findings suggest that language arousal nursing combined with heat preservation nursing improves anesthesia recovery in elderly patients undergoing spinal fracture surgery, leading to better outcomes and reduced adverse events. Conclusion: Combining language arousal and thermal insulation nursing enhances anesthesia recovery in elderly spinal fracture surgery patients, leading to optimized blood pressure, heart rate, reduced pain, and fewer anesthesia-related adverse events.
Subject(s)
Spinal Fractures , Humans , Aged , Oxygen Saturation , Anesthesia, General/adverse effects , Anesthesia, General/methods , Pain , ArousalABSTRACT
BACKGROUND: Coffee consumption has been associated with several adverse pregnancy outcomes, although data from randomized-controlled trials are lacking. We investigate whether there is a causal relationship between coffee consumption and miscarriage, stillbirth, birthweight, gestational age and pre-term birth using Mendelian randomization (MR). METHODS: A two-sample MR study was performed using summary results data from a genome-wide association meta-analysis of coffee consumption (N = 91â462) from the Coffee and Caffeine Genetics Consortium. Outcomes included self-reported miscarriage (N = 49â996 cases and 174â109 controls from a large meta-analysis); the number of stillbirths [N = 60â453 from UK Biobank (UKBB)]; gestational age and pre-term birth (N = 43â568 from the 23andMe, Inc cohort) and birthweight (N = 297â356 reporting own birthweight and N = 210â248 reporting offspring's birthweight from UKBB and the Early Growth Genetics Consortium). Additionally, a one-sample genetic risk score (GRS) analysis of coffee consumption in UKBB women (N up to 194â196) and the Avon Longitudinal Study of Parents and Children (N up to 6845 mothers and 4510 children) and its relationship with offspring outcomes was performed. RESULTS: Both the two-sample MR and one-sample GRS analyses showed no change in risk of sporadic miscarriages, stillbirths, pre-term birth or effect on gestational age connected to coffee consumption. Although both analyses showed an association between increased coffee consumption and higher birthweight, the magnitude of the effect was inconsistent. CONCLUSION: Our results suggest that coffee consumption during pregnancy might not itself contribute to adverse outcomes such as stillbirth, sporadic miscarriages and pre-term birth or lower gestational age or birthweight of the offspring.
Subject(s)
Abortion, Spontaneous , Stillbirth , Pregnancy , Child , Humans , Female , Birth Weight , Stillbirth/epidemiology , Stillbirth/genetics , Coffee/adverse effects , Abortion, Spontaneous/epidemiology , Gestational Age , Longitudinal Studies , Mendelian Randomization Analysis , Genome-Wide Association Study , Term BirthABSTRACT
The present study was conducted to investigate the effects of supranutritional selenium nanoparticles (SeNPs) on immune and antioxidant capacity in rats. Forty male Sprague-Dawley (SD) rats were randomly divided into four groups and given intragastric administration of SeNPs at doses of 0, 0.2, 0.4, and 0.8 mg Se/kg BW, respectively, for 2 weeks. Serum immune parameters, serum and organic tissues (liver, heart, kidney) antioxidant indices, and liver mRNA expression of glutathione peroxidase 1 (GPx1) and glutathione peroxidase 4 (GPx4) were examined. The results showed that supranutritional doses of 0.4 and 0.8 mg Se/kg BW SeNPs promoted the immune responses in serum. SeNPs administration improved antioxidant capacity in the liver and kidney, and the best improvement on antioxidant capacity was found in the kidney. Furthermore, intragastric administration of SeNPs upregulated mRNA expression of GPx1 and GPx4 in the liver. The results obtained indicated that SeNPs administration at supranutritional levels had beneficial effects on immune and antioxidant capacity and supplemental SeNPs at dose of 0.4 mg Se/kg BW exhibited the best response in SD rats.
Subject(s)
Nanoparticles , Selenium , Animals , Antioxidants , Liver , Male , Rats , Rats, Sprague-Dawley , Selenium/pharmacologyABSTRACT
The effects of selenium nanoparticles (SeNPs) on the antioxidant capacity in Sprague-Dawley (SD) rats were investigated. The rats were given intragastric administration of an SeNP suspension at doses of 0, 2, 4, and 8 mg Se/kg BW for two weeks. The antioxidant capacity in serum and organic tissues (liver, heart, and kidney) and the gene expression levels of glutathione peroxidase 1 (GPX1) and glutathione peroxidase 4 (GPX4) in the liver were measured. Buffalo rat liver (BRL) cell lines were further constructed to explore the cytotoxicity mechanism induced by SeNPs through the determination of antioxidant capacity; cell activity; apoptosis; and Caspase-3, Caspase-8, and Caspase-9 family activities. The results showed that SeNP administration over 4.0 mg Se/kg BW decreased the antioxidant capacities in the serum, liver, and heart and downregulated mRNA expression of GPX1 and GPX4 in the liver. The BRL cell line experiments showed that treatment with over 24 µM SeNPs decreased the viability of the cells and damaged the antioxidant capacity. Flow cytometry analysis showed that decreased cell viability induced by SeNPs is mainly due to apoptosis, rather than cell necrosis. Caspase-3 and Caspase-8 activities were also increased when BRL cells were treated with 24 µM and 48 µM SeNPs. Taken together, a nonlethal level of SeNPs could impair the antioxidant capacity in serum and organic tissues of rats, and the liver is the most sensitive to the toxicity of SeNPs. A pharmacological dose of SeNPs could lead to cytotoxicity and induce cell death through apoptosis and extrinsic pathways contributing to SeNP-induced apoptosis in BRL cells.
Subject(s)
Hepatocytes/pathology , Liver/pathology , Metal Nanoparticles/chemistry , Selenium/pharmacology , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , Apoptosis/drug effects , Caspases/metabolism , Cell Death/drug effects , Cell Line , Cell Survival/drug effects , Glutathione Peroxidase/genetics , Glutathione Peroxidase/metabolism , Hepatocytes/drug effects , Hepatocytes/ultrastructure , Liver/drug effects , Liver/ultrastructure , Male , Metal Nanoparticles/ultrastructure , Organ Specificity/drug effects , Oxidation-Reduction , Phospholipid Hydroperoxide Glutathione Peroxidase/genetics , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats, Sprague-Dawley , Glutathione Peroxidase GPX1ABSTRACT
The study was conducted to evaluate the effects of replacing inorganic trace minerals (ITMs) with respective low-dose complexed glycinate minerals (CGMs) on their bioavailability and retention during peak laying period of broiler breeders. In this experiment, 648 ZhenNing broiler breeders (23 weeks old) were randomly allocated to four treatments with six replicates (27 birds/replicate) and fed for 14 weeks including 2 weeks adaptation period. The treatments were T1-ITM, commercially recommended levels of ITMs (Cu, Zn, Fe, and Mn sulphates); T2-MIX, half of the minerals were supplemented with ITMs and half with CGMs; T3-L-CGMs, minerals were supplemented with CGMs (50% level of T1); and T4-M-CGMs, minerals were supplemented with CGMs (70% level of T1). The results showed that birds fed on ITM had lower bioavailability of Fe, Mn, and Zn (P < 0.05) than those fed on L-CGMs, but the highest (P < 0.01) bioavailability of Cu was found in those fed on MIX. Mineral retention (in serum, muscle, bone, and tissues) was not affected by reducing supplementation levels of trace minerals up to 50% of ITMs, but Zn (in serum, liver, kidney, heart, and albumen) and Fe (in serum and the yolk) retention was negatively affected (P < 0.05). In conclusion, replacing dietary ITMs with low-dose complexed glycinate minerals increases the apparent bioavailability of Fe, Mn, and Zn without compromising the mineral retention rates in most of the tissues tested.
Subject(s)
Chickens , Trace Elements , Animal Feed/analysis , Animals , Biological Availability , Diet/veterinary , Dietary Supplements , MineralsABSTRACT
BACKGROUND: This study evaluated the effects of dietary zinc oxide nanoparticles (nano-ZnOs) on growth performance, zinc status, intestinal morphology, microflora population, and immune response in weaned piglets. A total of 150 weaned piglets (9.37 ± 0.48 kg) were randomly allotted to five dietary treatments and fed with a basal diet (control), or the basal diet supplemented with nano-ZnOs at 150, 300, or 450 mg kg-1 , and 3000 mg kg-1 ZnO for 21 days. After a feeding test, six pigs from the control, 450 mg kg-1 nano-ZnOs and 3000 mg kg-1 ZnO groups were slaughtered. RESULTS: Compared with the control, dietary supplements of nano-ZnOs and ZnO could improve (P < 0.05) average daily weight gain (ADG), average daily feed intake (ADFI), and villus height to crypt depth ratio in the duodenum and jejunum, and decrease (P < 0.05) diarrhea incidence. Zinc retention in the serum, heart, liver, spleen and kidney of pigs supplemented with nano-ZnOs and ZnO was increased (P < 0.05). Nano-ZnOs decreased (P < 0.05) the zinc excretion compared with conventional ZnO. Lower Escherichia coli counts in the cecum, colon, and rectum were observed (P < 0.05) in the nano-ZnOs group compared with the other groups. Compared with the control, ZnO and nano-ZnOs increased (P < 0.05) the serum concentration of IgA, IL-6, and TNF-α, and decreased (P < 0.05) the concentration of IgM. CONCLUSION: These results indicated that low doses of nano-ZnOs can have beneficial effects on growth performance, intestinal morphology and microflora, and immunity in weanling pigs, which are similar to the effects of pharmacological dosages of conventional ZnO. Nano-ZnOs may reduce mineral excretion, which may reduce environmental challenges. © 2018 Society of Chemical Industry.
Subject(s)
Gastrointestinal Microbiome , Intestines/growth & development , Nanoparticles/metabolism , Swine/immunology , Zinc Oxide/metabolism , Animals , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Dietary Supplements/analysis , Female , Intestines/anatomy & histology , Intestines/immunology , Intestines/microbiology , Male , Nanoparticles/microbiology , Swine/growth & development , Swine/metabolism , Swine/microbiology , WeaningABSTRACT
This study investigated the effects of replacement of inorganic trace minerals (ITMs) by organic trace minerals (OTMs) on tissue mineral retention and fecal excretion in "Zhen Ning" yellow feather broiler breeders. Six hundred hens (initial BW: 1.70 ± 0.07 kg) aged 40 weeks were randomly divided into five treatments, with four replicates of 30 broiler breeders each. Experimental treatments were as follows: (1) ITM (Cu, Zn, Fe, Mn, Se providing commercially recommended concentrations), (2) L-ITM (50% of the ITM, except for Se), (3) VL-OTM (37.5% of the ITM, except for Se), (4) L-OTM (equivalent to L-ITM), and (5) OTM (62.5% of the ITM, except for Se). The duration of the study was 10 weeks including 2 weeks for adaptation. Compared with the L-ITM treatment, high-level supplementation of minerals in ITM and OTM increased the concentration of serum Mn and Se, pectoral Fe and pancreas Cu, and Fe (P < 0.05). Birds fed with OTM dietary exhibited comparable mineral retention in muscle compared with ITM. Differences were observed between L-ITM and L-OTM in serum Mn and Se, pectoral Fe, Zn, and Se, and heart Se with L-OTM retaining higher mineral concentrations than L-ITM (P < 0.05). L-OTM retained identical concentration with ITM treatment, except for the pancreatic Fe. All three organic diets reduced the Zn in excreta compared with the two inorganic diets (P < 0.05). This study indicates that replacement of dietary ITMs by OTMs improved mineral deposition in tissues and reduced fecal mineral excretion in broiler breeders under the conditions of this study.
Subject(s)
Feces/chemistry , Minerals/analysis , Minerals/metabolism , Trace Elements/analysis , Trace Elements/metabolism , Animals , Chickens , Dietary Supplements , FemaleABSTRACT
Aberrant activation of phosphatidylinosito-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT) signaling in cancer has led to pursuit of inhibitors for targeting this pathway. However, inhibitors of PI3K and AKT have failed to yield efficacious results without adverse effects. Here, we screened a library containing 441 authenticated traditional chinese medicine (TCM) plant extracts by examining their effect on cell viability of a human mammary epithelial cell line HMEC-PIK3CAH1047R, which expresses mutant PIK3CAH1047R and has constitutively active AKT signaling. We found that Oridonin, an extract from Rabdosia rubescens, reduced cell viability to the greatest extent. Oridonin binds to AKT1 and potentially functions as an ATP-competitive AKT inhibitor. Importantly, Oridonin selectively impaired tumor growth of human breast cancer cells with hyperactivation of PI3K/AKT signaling. Moreover, Oridonin prevented the initiation of mouse mammary tumors driven by PIK3CAH1047R. Our results suggest that Oridonin may serve as a potent and durable therapeutic agent for the treatment of breast cancers with hyperactivation of PI3K/AKT signaling.
ABSTRACT
BACKGROUND: High platelet reactivity (HPR) during clopidogrel treatment predicts postpercutaneous coronary intervention (PCI) ischemic events strongly and independently. Tongxinluo capsules (TCs) are a traditional Chinese medicine formulation used as antiplatelet treatment. However, its efficacy against HPR is not known. The aim of the present study was to evaluate the effects of TCs in acute coronary syndrome (ACS) patients with HPR. METHODS: This multicenter, randomized, double-blind, placebo-controlled study prospectively analyzed 136 ACS patients with HPR who underwent PCI. The patients were enrolled from November 2013 to May 2014 and randomized to receive placebo or TCs in addition to standard dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. The primary end points were the prevalence of HPR at 30 days and the mean change in P2Y12reaction units (PRUs) between baseline and 30 days. Survival curves were constructed with Kaplan-Meier estimates and compared by log-rank tests between the two groups. RESULTS: Both groups had a significantly reduced prevalence of HPR at 30 days versus baseline, but the TC group, compared with the placebo group, had greater reduction (15.8% vs. 24.8%, P = 0.013), especially among patients with one cytochrome P450 2C19 loss of function (LOF) allele (χ2 = 2.931, P = 0.047). The TC group also had a lower prevalence of HPR (33.3% vs. 54.2%, t = 5.284, P = 0.022) and superior performance in light transmittance aggregometry and higher levels of high-sensitivity C-reactive protein (hsCRP), but the composite prevalence of ischemic events did not differ significantly (χ2 = 1.587, P = 0.208). CONCLUSIONS: In addition to standard DAPT with aspirin and clopidogrel, TCs further reduce PRU and hsCRP levels, especially in patients carrying only one LOF allele. The data suggest that TCs could be used in combination therapy for ACS patients with HPR undergoing PCI.
Subject(s)
Acute Coronary Syndrome/drug therapy , Drugs, Chinese Herbal/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Aged , Aspirin/therapeutic use , Blood Platelets/drug effects , Capsules/therapeutic use , Clopidogrel , Double-Blind Method , Female , Humans , Male , Middle Aged , Percutaneous Coronary Intervention , Platelet Aggregation/drug effects , Ticlopidine/analogs & derivatives , Ticlopidine/therapeutic useABSTRACT
Triptolide (TPL) is an active compound extracted from a Chinese herbal medicine tripterygium wilfordii Hook. f. (Celastraceae), which has been used as an anti-inflammatory drug for years. It also inhibits the growth and proliferation of different types of cancer cells. The inhibitory effect of TPL on angiogenesis after chemical-induced corneal inflammation was studied in vivo. The effects of TPL on the proliferation, apoptosis, migration, and tube formation of rat aortic endothelial cells (RAECs) were studied in vitro. Cell proliferation and apoptosis were measured by MTT assay and flow cytometry, respectively. Migration was analyzed using the scratch wound healing assay and transwell assay. Tube formation assay was used to examine angiogenesis. Real-time PCR and Western blot were used to determine the expression of vascular endothelial growth factor A (VEGFA) and VEGFC. To study the in vivo effects of TPL, the mouse model of alkali burn-induced corneal angiogenesis was used. The angiogenesis was analyzed by determining the density of the newly generated blood vessels in corneas. We found that TPL induced apoptosis and inhibited the proliferation of RAECs in a dose-dependent manner. TPL inhibited migration and tube formation of RAECs and decreased the expression of VEGFA and VEGFC in vitro. Furthermore, TPL suppressed alkali burn-induced corneal angiogenesis and inhibited the expression of VEGFA and VEGFC in corneas in vivo. In conclusion, topical TPL as a pharmacological agent has the ability to reduce angiogenesis in cornea and may have clinical indications for the treatment of corneal angiogenesis diseases which have to be further explored. Anat Rec, 300:1348-1355, 2017. © 2017 Wiley Periodicals, Inc.
Subject(s)
Alkalies/toxicity , Corneal Neovascularization/prevention & control , Diterpenes/pharmacology , Eye Burns/prevention & control , Neovascularization, Pathologic/prevention & control , Phenanthrenes/pharmacology , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor C/metabolism , Animals , Cell Movement/drug effects , Cell Proliferation/drug effects , Corneal Neovascularization/chemically induced , Corneal Neovascularization/metabolism , Epoxy Compounds/pharmacology , Eye Burns/chemically induced , Eye Burns/metabolism , Female , Mice , Mice, Inbred BALB C , Neovascularization, Pathologic/chemically induced , Neovascularization, Pathologic/metabolism , RatsABSTRACT
BACKGROUND: Preoperative platelet rich plasma (PRP) harvest has been used in cardiopulmonary surgery for more than 10 years. There is no previous study dealing with PRP in bilateral total hip replacement. This study was to investigate the effects of PRP on blood saving and blood coagulation function in patients with bilateral total hip replacement. PATIENTS AND METHODS: A prospective, randomized, clinical trial was conducted. Sixty patients were enrolled, including 30 patients undergoing PRP in the PRP group and 30 controls. The surgery time, total transfusion volume, blood loss, allogenic blood transfusion, autologous blood transfusion, urine volume, drainage volume, some blood parameters (including Fibrinogen, D-dimer, Prothrombin time, international normalizedratio, activated partial thromboplastin time, Platelet, Haemoglobin B), thrombelastogram (TEG) and blood-gas parameters were studied in the perioperative stage. The measurement data were analyzed statistically. RESULTS: There was no statistical difference between the two groups in baseline characteristics, surgery time, total transfusion volume, blood loss, autologous blood transfusion, etc. Allogenic blood transfusion in the PRP group was less than the control group with statistical difference (p = 0.024). Fibrinogen in the PRP group was higher than the control group (p = 0.008). Among the TEG indicators, activated clotting time and coagulation time K in the PRP group were less than the control group. Clotting rate and maximum amplitude in the PRP group were higher. The blood-gas parameters presented no statistical difference. CONCLUSION: The results suggested that PRP probably played a positive role in blood coagulation function as well as blood saving in patients with bilateral total hip replacement.
Subject(s)
Arthroplasty, Replacement, Hip , Blood Loss, Surgical/prevention & control , Blood Transfusion, Autologous/methods , Platelet Transfusion/methods , Plateletpheresis/methods , Preoperative Care/methods , Adult , Aged , Blood Coagulation , Blood Coagulation Tests , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Hemoglobins/analysis , Humans , Male , Middle Aged , Prospective Studies , Single-Blind MethodABSTRACT
PURPOSE: This study was designed to investigate the risk of local anesthetic toxicity and efficacy of simultaneous bilateral axillary brachial plexus block performed under the guidance of ultrasound or a neurostimulator. METHODS: One hundred and twenty patients who were anesthetized with bilateral axillary plexus block simultaneously between February 2012 and March 2014 were enrolled in the study. The patients were anesthetized under the guidance of a neurostimulator (group N, n = 60) or ultrasound (group U, n = 60). The block performance time, procedure-related pain, adverse events, total and free plasma concentrations of ropivacaine, and other data were recorded. The comparison was analyzed statistically. RESULTS: The block performance time, and onset of the sensory and motor block, of group N was longer than that of group U (p < 0.001). The procedure-related pain of group N was more serious than that of group U (p < 0.05). The patient satisfaction rate of group U was higher than that of group N (p < 0.05). The total plasma concentrations of ropivacaine in group N were comparable to those of group U, except for the value at 50 min after injection (p < 0.05). The free plasma concentrations of ropivacaine of group N at 5 min were significantly higher than that of group U (p < 0.001). No apparent serious adverse events were observed perioperatively in both groups. CONCLUSIONS: Simultaneous bilateral axillary brachial plexus block guided by neurostimulator or ultrasound in bilateral distal upper extremity surgery seems to have a low risk of local anesthetic toxicity and to be effective. The ultrasound-guided block is superior in terms of providing the same degree of anesthesia with shorter duration, less pain, and faster onset of sensory and motor blockades, which is important in clinical practice.
Subject(s)
Amides/administration & dosage , Anesthesia, Local/methods , Brachial Plexus Block/methods , Adult , Female , Humans , Injections , Male , Middle Aged , Pain/etiology , Patient Satisfaction , Prospective Studies , Ropivacaine , Time Factors , UltrasonographyABSTRACT
In order to investigate whether Yinchenhao decoction (YCHD) attenuates hepatic fibrogenesis in the bile duct ligation (BDL) model via recovering and restoring the self-regulation and balance of the renin-angiotensin system (RAS), 33 specific-pathogen-free (SPF) male Sprague-Dawley rats with common BDL and scission were randomly divided into five groups as follows: G1, the sham group (n=4); G2, BDL 7-day group (n=5); G3, BDL+YCHD 430 mg/mL (n=8); G4, BDL+losartan 0.65 mg/mL (ARB group, n=8); G5, model group (BDL without any treatment, n=8). YCHD and losartan (10 mL·kg(-1)·day(-1)) were given by gastric gavage for 16 days following BDL in G3 and G4 groups, respectively. The effect of YCHD on liver fibrosis and the detailed molecular mechanisms were assessed by liver function including total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IDBIL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Histological changes were observed by transmission electron microscopy (TEM) and Masson trichrome staining. Western blotting was used to detect the protein expression level of the renin-angiotensin system (RAS) components including angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AT1R), ACE2, angiotensin II (AngII) as well as transforming growth factor ß1 (TGFß1). The experimental data were analyzed by principle component analytical method of pattern recognition. The results showed that biochemically, serum TBIL, DBIL, IDBIL, ALT and AST levels were markedly increased following BDL as compared with the sham group (P<0.05). Serum TBIL, IDBIL and DBIL levels in G3 group were dramatically decreased as compared with G5 and G4 groups (P<0.05). Serum AST level in G3 was significantly lowered than in G5 group (P<0.05), but there was no significant difference in ALT among G3, G4 and G5 groups (P>0.05). Histologically, livers in G3 group showed less hepatocytes necrosis, less bile duct hyperplasia and less collagen formation than in G4 and G5 groups. The protein expression levels of ACE2, ACE, AngII, AT1R and TGFß1 in G2, G3 and G4 groups were significantly higher than in sham group (P<0.05), and lower than in G5 group (P<0.05). However, the differences among G2, G3 and G4 groups were not significant (P>0.05). ACE2 protein expression in G3 group was significantly higher than in G2 group (P<0.05) and there was no significant difference in comparison with G4 group (P>0.05). Moreover, the protein expression of TGFß1 in G3 group was significantly lower than in G5 and G4 groups (P<0.05). Our findings suggest that the antifibrotic effects of YCHD may be associated with the decreased classical RAS pathway components and TGFß1 downexpression so as to recover and rebuild self-regulation of the RAS by elevating the protein expression of ACE2.
Subject(s)
Drugs, Chinese Herbal/administration & dosage , Liver Cirrhosis/prevention & control , Liver/drug effects , Renin-Angiotensin System/drug effects , Animals , Disease Models, Animal , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Gene Expression Regulation/drug effects , Liver/pathology , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Liver Function Tests , Losartan/administration & dosage , Male , Rats , Rats, Sprague-DawleyABSTRACT
Icaritin (ICT) is a main aglycone and also active intestinal metabolite of prenylflavonoids from the Chinese medicine Herba Epimedii. In the present study, the oral absorption and excretion of this compound was investigated using rats for exploring its fate in the body, so as to better understanding its in vivo pharmacological activities. The free (parent) and total (parent plus conjugated metabolites) ICT concentrations in rat plasma, urine and bile, after intravenous (i.v.) and oral administration both at 5mg/kg, were determined before and after enzymatic hydrolysis with ß-glucuronidase/sulphatase, respectively, by a HPLC-UV method. The results showed that free ICT plasma concentration after i.v. dose was rapidly decreased with average t(1/2, λ) of 0.43 h, while the total ICT concentration was decreased slowly with t(1/2, λ) of 6.86 h. The area under the curve of ICT conjugated metabolites was about 11-fold higher than that of free ICT. The majority of ICT in the body was excreted from the bile with 68.05% of dose over 8 h after i.v. dosing, in which only 0.15% was in parent form. While very little amount of ICT was excreted from the urine with 3.01% of dose over 24 h, in which the parent form was 0.62%. After oral administration, very little amount of parent ICT was detected only in 0.5, 1 or 2 h plasma samples with the concentration less than LOQ, however, its total plasma concentration after enzymatic hydrolysis treatment was at relative high level with average maximum concentration of 0.49 µg/ml achieved at 1h post dose. The oral bioavailability of ICT was 35% of dose, estimated by its total plasma drug concentrations. It is concluded that ICT can be easily absorbed into the body, and then rapidly conversed to its conjugated metabolites, and finally removed from the body mainly by biliary excretion.
Subject(s)
Bile/chemistry , Drugs, Chinese Herbal/chemistry , Flavonoids/pharmacokinetics , Absorption , Administration, Oral , Animals , Biological Availability , Flavonoids/blood , Flavonoids/chemistry , Flavonoids/urine , Injections, Intravenous , Male , Rats , Rats, Sprague-DawleyABSTRACT
Effect of phosphorus on the production of microcystin was researched. The effects of soluble reactive phosphorus (SRP) on the growth of cells and on the production of Microcystin were studied. In addition, the efficiency of four different phosphorus compounds was researched. The results showed that microcystin increased with the increase of SRP, and c(TP) = 0.55 mg x L(-1) was the best growth concentration. When c(TP) < or = 0.55 mg x L(-1), the microcystin production increased with the increase of phosphorus concentration and was the lowest without phosphorus. Moreover, when c(TP) > 0.55 mg x L(-1), the microcystin was restrained by the content of phosphorus. At the same time, the effects of three inorganic substance of different phosphorus forms (K3PO4, K2HPO4, and KH2PO4) were no significant difference, but their effects on the production of microcystis were larger than organic phosphorus of sodium beta-glycerophosphate (GP).
Subject(s)
Microcystins/biosynthesis , Microcystis/metabolism , Phosphorus/pharmacology , Culture Techniques , Glycerophosphates/pharmacology , Microcystis/drug effects , Microcystis/growth & developmentABSTRACT
A highly sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of forsythiaside in rat plasma using epicatechin as internal standard. The analytes were extracted by solid-phase extraction and chromatographied on a C(18) column eluted with a gradient mobile phase of acetonitrile and water both containing 0.2% formic acid. The detection was performed by negative ion electrospray ionization in multiple reaction monitoring mode, monitoring the transitions m/z 623-->161 and m/z 289-->109 for forsythiaside and epicatechin, respectively. The assay was linear over the concentration ranges of 2.0-50.0 and 50.0-5000.0ng/mL with limits of detection and quantification of 0.2 and 1.0ng/mL, respectively. The precision was <10.8% and the accuracy was >91.9%, and extraction recovery ranged from 81.3% to 85.0%. This method was successfully applied to a pharmacokinetic study of forsythiaside in rats after intravenous (20mg/kg) and oral (100mg/kg) administration, and the result showed that the compound was poorly absorbed with an absolute bioavailability being approximately 0.5%.
Subject(s)
Chromatography, Liquid/methods , Glycosides/blood , Tandem Mass Spectrometry/methods , Animals , Area Under Curve , Catechin/analysis , Catechin/chemistry , Catechin/pharmacokinetics , Drug Stability , Drugs, Chinese Herbal/analysis , Drugs, Chinese Herbal/pharmacokinetics , Glycosides/chemistry , Glycosides/pharmacokinetics , Least-Squares Analysis , Male , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Sensitivity and Specificity , Solid Phase ExtractionABSTRACT
3,6'-Disinapoylsucrose (DSS), a major active component of traditional Chinese medicine Yuan-Zhi (the roots of Polygala tenuifolia), has significant effects for neuroprotection and improving learning memory. In order to explore the pharmacokinetic properties of DSS so as to further understand its in vivo activities, a sensitive LC-MS/MS method was developed for determination of DSS in rat plasma and applied to a pharmacokinetic study in the present study. After treatment by protein precipitation, the plasma sample was separated on a C(18) HPLC column and analyzed by a mass spectrometry under positive electrospray ionization. Multiple-reaction monitoring was employed to measure the ion transition at m/z 777.4 --> 409.2 for DSS and m/z 557.2 --> 309.1 for forsythin as internal standard. The method was linear over the studied concentration range of 0.5-1000.0 ng/mL. The precision and accuracy ranged from 1.4 to 18.4%, and from -3.7 to -9.5%, respectively, for within-day and between-day assay. Extraction recovery was higher than 86.6%. The limits of detection and quantification were 0.3 and 0.5 ng/mL, respectively. The present method was successfully applied to a pharmacokinetic study. DSS was found to have poor oral absorption with only about 0.5% bioavailability.
Subject(s)
Chromatography, High Pressure Liquid/methods , Coumaric Acids/blood , Sucrose/analogs & derivatives , Tandem Mass Spectrometry/methods , Animals , Limit of Detection , Magnetic Resonance Spectroscopy , Rats , Reproducibility of Results , Sucrose/bloodABSTRACT
This study aims to formulate and evaluate bioavailability of a self-nanoemulsified drug delivery system (SNEDDS) of a poorly water-soluble herbal active component oleanolic acid (OA) for oral delivery. Solubility of OA under different systems was determined for excipient selection purpose. Four formulations, where OA was fixed at the concentration of 20 mg/g, were prepared utilizing Sefsol 218 as oil phase, Cremophor EL and Labrasol as primary surfactants, and Transcutol P as cosurfactant. Pseudo-ternary phase diagrams were constructed to identify self-emulsification regions for the rational design of SNEDDS formulations. Sefsol 218 was found to provide the highest solubility among all medium-chained oils screened. Efficient self-emulsification was observed for the systems composing of Cremophor EL and Labrasol. The surfactant to cosurfactant ratio greatly affected the droplet size of the nanoemulsion. Based on the outcomes in dissolution profiles, stability data, and particle size profiles, three optimized formulations were selected: Sefsol 218/Cremophor EL/Labrasol (50:25:25, w/w), Sefsol 218/Cremophor EL/Labrasol/Transcutol P (50:20:20:10, w/w), and Sefsol 218/Cremophor EL/Labrasol/Transcutol P (50:17.5:17.5:15, w/w). Based on the conventional dissolution method, a remarkable increase in dissolution was observed for the SNEDDS when compared with the commercial tablet. The oral absorption of OA from SNEDDS showed a 2.4-fold increase in relative bioavailability compared with that of the tablet (p < 0.05), and an increased mean retention time of OA in rat plasma was also observed compared with that of the tablet (p < 0.01). These results suggest the potential use of SNEDDS to improve dissolution and oral bioavailability for poorly water-soluble triterpenoids such as OA.