Continuous Intravenous Injection Research Articles

The effect of sequential perioperative intravenous tranexamic acid in reducing postoperative blood loss and hidden blood loss after posterior lumbar interbody fusion: a randomized controlled trial.

Tranexamic acid (TXA) has previously been shown to be effective in reducing intraoperative blood loss (IBL) and transfusion requirements in spine surgery. A conventional TXA regimen is a simple preoperative or intraoperative administration. However, the hyperfibrinolysis caused by surgical trauma lasts at least 24 h, and a single dose of TXA cannot cover the whole process of hyperfibrinolysis. Moreover, its ability to control postoperative blood loss (PBL) may be insufficient. Therefore, this study aimed to explore the effects and safety of sequential perioperative intravenous TXA for reducing bleeding after posterior lumbar interbody fusion (PLIF). Patients requiring PLIF were randomly divided into two groups. All patients were intravenously injected with 1 g of TXA 15 min before skin resection. Every day after the surgery, 200 ml saline was intravenously injected for 1-3 days in Group A, while Group B received 1 g of TXA instead of saline. The total blood loss (TBL), IBL, PBL, HCT, Hb, blood transfusion volume, inflammation-related indicators, and complications were recorded. TBL, PBL, and hidden blood loss (HBL) in Group B were significantly lower than those in Group A (P < 0.05). The maximum decreases in HCT and Hb in Group B were also significantly lower than those in Group A (P < 0.05), and the drainage removal time (DRT) was sooner in Group B than in Group A (P = 0.003). On the 3rd and 5th days after surgery, the level of CRP in Group B was significantly lower than that in Group A (P < 0.05). Similarly, IL-6 levels were significantly lower in Group B for the first 5 days postoperatively (P < 0.001). Sex, operation time, level of decompression, length of incision, and change in HCT were significant predictors of both TBL and HBL. TBL was also significantly associated with BMI and preoperative fibrinogen, while postoperative TXA was a significant predictor of HBL only. Intravenous injection of 1 g of TXA 15 min before skin resection combined with continuous intravenous injection of 1 g of TXA 1 to 3 days after PLIF can reduce postoperative bleeding and shorten the time to drainage tube removal. In addition, it can also inhibit the postoperative inflammatory response. ChiCTR2200056210.

Determination of the Blood Glucose Concentration of a Patient During Continuous Intravenous Injection Using Anuj Transform

Determination of the Blood Glucose Concentration of a Patient During Continuous Intravenous Injection Using Anuj Transform

Multimodal Analgesia for Accelerated Rehabilitation after Total Knee Arthroplasty: A Randomized, Double-Blind, Controlled Trial on the Effect of the Co-Application of Local Infiltration Analgesia and Femoral Nerve Block Combined with Dexmedetomidine.

Multimodal postoperative pain regimens are widely used following total knee arthroplasty (TKA). However, there are few studies on the rehabilitation of the co-application of local infiltration analgesia (LIA) and femoral nerve block (FNB) combined with dexmedetomidine (DEX) for patients undergoing TKA. This study aimed to investigate the effect of LIA plus FNB and co-application of perioperative DEX on TKA outcomes. 95 patients were randomized into two groups. Patients in group B (n = 48) received a single preoperative FNB and LIA. Patients in group A (n = 47) received FNB and LIA, as well as continuous intravenous injection of DEX starting from the induction of anesthesia to postoperative day 2. All patients were allowed patient-controlled analgesia postoperatively. Visual analog scale (VAS) scores, knee range of motion (ROM) degrees, narcotic consumption, length of hospital stay (LOS), complications, Hospital for Special Surgery (HSS) scores and Montreal Cognitive Assessment-Basic (MoCA-B) Scores were recorded. In group A, the mean VAS scores at rest and during movement were lower, the amount of rescue analgesia was decreased, first time of ambulation was reduced, ROM was improved, MoCA-B Scores were increased, LOS was shorter, HSS scores were higher postoperatively compared with group B (all p &lt; 0.05). Our study indicated multimodal analgesia involving a single FNB and LIA combined with DEX accelerates rehabilitation for patients undergoing TKA.

New-onset type 1 diabetes mellitus as a delayed immune-related event after discontinuation of nivolumab: A case report

Rationale:Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, they may cause immune-related adverse events. Although there have been a few reports of new-onset type 1 diabetes mellitus (T1DM) during ICI treatment, T1DM as a delayed immune-related event after discontinuing immunotherapy is extremely rare. Herein, we report the case of an elderly veteran who presented with diabetic ketoacidosis 4 months after the discontinuation of treatment with nivolumab.Patient concerns:A 74-year-old veteran was treated with second-line nivolumab for advanced non–small cell lung cancer. After 9 treatment cycles, the administration was discontinued due to fatigue. Four months later, he was admitted to the emergency department in a stuporous mental state and hyperglycemia, with high glycosylated hemoglobin levels (10.6%). C-peptide levels were significantly decreased, with negative islet autoantibodies.Diagnoses:We diagnosed nivolumab-induced T1DM. There were no laboratory results indicating a new thyroid dysfunction or adrenal insufficiency, which are typical endocrine adverse reactions.Interventions:Since the hypothalamic and pituitary functions were preserved and only the pancreatic endocrine capacity was impaired, we administered continuous intravenous insulin injections, with fluid and electrolyte replacement.Outcomes:His serum glucose levels decreased, and symptoms improved; hence, on the 8 day of hospitalization, we switched to multiple daily insulin injections.Lessons:The present case indicates that regular glucose monitoring and patient education are needed for diabetic ketoacidosis after the discontinuation of ICI therapy.

Propofol Regulates the TLR4/NF-κB Pathway Through miRNA-155 to Protect Colorectal Cancer Intestinal Barrier.

Surgery for colorectal cancer (CRC) can cause damage to the intestinal mucosal barrier and lead to bacterial invasion. This study mainly analyzed whether propofol (PPF) could protect the intestinal mucosal barrier damage caused by CRC surgery, and explored its molecular mechanism. A mouse CRC model was constructed using azomethane and dextran sulfate sodium. During anesthesia, continuous intravenous injection of PPF was used for intervention. The influences of PPF on intestinal mucosal permeability and bacterial invasion were detected. The levels of microRNA (miR)-155, Toll-like receptor 4 (TLR4)/NF-κB in the intestinal mucosa, and the location of miR-155 were detected by fluorescence in situ hybridization (FISH). Mouse macrophages were used to analyze the regulation of miR-155 on the secretion of inflammatory cytokines through the TLR4/NF-κB pathway. PPF treatment promoted the expression of tight junction protein in the intestinal mucosa, protected the intestinal barrier, inhibited the translocation of intestinal bacteria, and increased the level of the beneficial bacterium Lactobacillus on the mucosal surface. In addition, PPF treatment could inhibit the expression of miR-155, TLR4/NF-KB, and reverse inflammatory response. miR-155 was expressed in macrophages of intestinal mucosa tissue. Overexpression of miR-155 promoted the nuclear translocation of NF-κB and the expression of inflammatory cytokines in macrophages. The use of VIPER to inhibit TLR4 reversed the pro-inflammatory effects of miR-155. PPF might inhibit the activation of the NF-κB pathway by downregulating miR-155 expression, thereby reducing the secretion of inflammatory cytokines. This might be the mechanism by which PPF protected the intestinal barrier of CRC surgical model mice.

Central pontine myelinolysis during treatment of hyperglycemic hyperosmolar syndrome: a case report

BackgroundCentral pontine myelinolysis (CPM) is a non-inflammatory demyelinating lesion of the pons. CPM and extrapontine demyelination (EPM) are together termed osmotic demyelination syndrome (ODS), a known and serious complication of acute correction of hyponatremia. Conversely, hyperglycemic hyperosmolarity syndrome (HHS) develops in patients with type 2 diabetes who still have some insulin secretory ability due to infection, non-compliance with treatment, drugs, and coexisting diseases, and is often accompanied by ketosis. HHS represents a life-threatening endocrine emergency (mortality rate, 10–50%) associated with marked hyperglycemia and severe dehydration. HHS may develop ODS, and some cases have been associated with hypernatremia.Case presentationThe patient was an 87-year-old woman with hyperglycemia, dehydration, malnutrition, and potential thrombus formation during long-term bed rest. HHS was suspected to have developed due to progression of hyperglycemia and dehydration caused by pneumonia. Furthermore, ketoacidosis developed from ketosis and prerenal renal failure associated with circulating hypovolemia shock, which was also associated with disseminated intravascular coagulation. Treatment was started with continuous intravenous injection of fast-acting insulin and low-sodium replacement fluid. In addition, ceftriaxone sodium hydrate, heparin sodium, thrombomodulin α, human serum albumin, and dopamine hydrochloride were administered. Blood glucose, serum sodium, serum osmolality, and general condition (including vital, infection/inflammatory findings, and disseminated intravascular coagulation) improved promptly, but improvements in disturbance of consciousness were poor. Diffusion-weighted imaging of the brain 72 h after starting treatment showed no obvious abnormalities, but high-intensity signals in the midline of the pons became apparent 30 days later, leading to definitive diagnosis of CPM.ConclusionsFluctuation of osmotic pressure by treatment from hyperosmolarity due to hyperglycemia and hypernatremia in the presence of risk factors such as malnutrition, severe illness, and metabolic disorders may be a cause of CPM onset. When treating HHS with risk factors, the possibility of progression to ODS needs to be kept in mind.

Effects of nicorandil infusion on ECG parameters in patients with unstable angina pectoris and percutaneous coronary intervention.

BackgroundPercutaneous coronary intervention (PCI) is effective in treating patients with acute coronary syndrome (ACS) but is associated with some serious complications. Nicorandil is an anti‐anginal agent acting to improve microvascular circulation and to increase coronary blood flow. The objective of this article is to evaluate the effects of intracoronary injection followed with continuous intravenous injection of nicorandil on ECG parameters in patients with unstable angina pectoris (UA) undergoing PCI.MethodsA single‐center, self‐controlled clinical trial was conducted at the Second Hospital of Tianjin Medical University between January 2019 and April 2019. Sixty‐three consecutive patients with UA who received coronary angiography and selective PCI were enrolled. ECG was recorded and analyzed before and 24 hr after nicorandil infusion.ResultsPatients were divided into three groups: control group (n = 23, aged 63.43 ± 12.55 years), short‐term, and prolonged use with nicorandil group (n = 20 and 20, aged 66.45 ± 8.06 years and 65.80 ± 9.49 years, respectively). Clinical characteristics and ECG parameters were similar before PCI among three groups (p > .05). In nicorandil treatment groups, intervals of QTd and Tp‐e in patients post‐PCI were significantly shorter than that in control and pre‐PCI (p < .05).ConclusionsNicorandil infusion reduces QTd and Tp‐e interval in patients with UA. Further studies will be needed to determine whether these electrophysiological changes are associated with a reduction of ventricular arrhythmias and improved outcomes.

Symptom management in two adolescent girls with cancer who were effectively sedated by continuous intravenous injection of midazolam at home for relief of end-of-life distress

Symptom management in two adolescent girls with cancer who were effectively sedated by continuous intravenous injection of midazolam at home for relief of end-of-life distress

Study of sevoflurane/remifentanil coadministration on improving emergence and recovery characteristics of patients following general anaesthesia with sevoflurane

Objective: To investigate the effects of remifentanil infusion on emergence and recovery characteristics of patients with thoracoscopic lobectomy following general anaesthesia with sevoflurane. Methods: One hundred patients, who were aged 37 to 65 years with American Society of Anesthesiologists (ASA) physical status 1-2, and scheduled for elective thoracoscopic lobectomy under general anaesthesia in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from February 2016 to August 2016, were allocated to receive sevoflurane maintenance regimen(group S, n=50)or sevoflurane/remifentanil maintenance regimen(group SR, n=50)by random digital table. After routine induction and intubation, anaesthesia was maintained with 2% sevoflurane in group S and 1.5% sevoflurane/remifentanil(continuous intravenous injection at rate of 4 μg·kg(-1)·h(-1))coadministration in group SR respectively, with intermittent intravenous infusion of sulfentanil. Haemodynamic variables were collected at different time points and compared between two groups. Awaking time and extubation time, incidences of serious coughing and agitation were evaluated during emergence.Postoperative pain, nausea and cather-related bladder discomfort(CRBD)were evaluated in post anesthesia care unit. Results: Compared with group S, the arterial blood pressure and heart rate were significantly lower in group SR at extubation(all P<0.05). Time to awaking and to extubation in group SR were (4.2±2.1) min and (4.8±3.1)min respectively, in group S were (12.7±3.4) min and (15.4±4.1)min.The difference between two groups were statistically significant (t=-15.040, 14.582, all P<0.05). The incidences of serious coughing and agitation in group S were 48% and 58%, which were greater than those of group SR(6% and 10%). The difference were statistically significant(χ(2)=20.294, 23.574, all P<0.05). The NRS and incidence of complaining CRBD were similar in both groups(all P>0.05). Conclusion: Compared with sevoflurane maintenence, coadministration of remifentanil and sevoflurane maintenance regimen provides better emergence and recovery which are characterized by faster awakening and extubation with a lower incidence of emergence coughing and agitation.

Vascular regeneration by injection of recombinant vascular endothelial growth factor into vaginal muscular brachial plexus syndrome model via tail vein in rats

Objective To explore the effect of vascular endothelial growth factor (VEGF) on portal pressure in rats with Budd-Chiari syndrome (B-CS). Methods Male Sprague-Dawley (S-D) rats were used to make 30% narrow of the inferior vena cava by surgery. The experiments were divided into B-CS + VEGF group (group B, n=12), B-CS + normal saline group (group C, n=12) and sham operation group (group A, n=15). The animals in group B received continuous intravenous injection of VEGF (6 μg/kg body weight every day), and those in group A and C were given the same amount of normal saline for 4 weeks. The portal vein pressure was measured at 8th week postoperatively. Pathological changes of the liver were observed by HE staining. Intrahepatic vascular density was quantified by immunohistochemical staining. Results The rate of B-CS formation in rats was about 60%. B-CS rats showed obstruction of inferior vena cava and main hepatic vein, the swelling of the liver and spleen, the congestion of the mesentery, the enlargement of the abdominal vein and portal vein, and significantly elevated portal vein pressure [group A: (10.00±0.38) mmHg(1 mmHg=0.133 kPa); group B: (15.50±0.59) mmHg; group C: (17.25±0.48) mmHg, P=0.016], reduced the balloon degeneration of liver cell (P=0.007). As compared with the saline group (2.80±0.38), the collateral vessel angiogenesis was significantly increased in the liver and esophagus and gastric fundus (8.20±0.53, P=0.000). Portal vein pressure reduced, and ascites decreased, the balloon degeneration of liver cells, and liver and spleen congestion (P=0.028) alleviated in the VEGF group. Conclusion VEGF can improve the portal hypertension in B-CS rats by promoting angiogenesis in the medial and lateral branches of the liver. Key words: Budd-Chiari syndrome; Portal hypertension; Vascular endothelial growth factor

Changes of small intestinal villi microcirculation in sidestream dark-field imaging with different target blood pressure in rabbits during endotoxin shock

Changes of small intestine villus microcirculation perfusion in sidestream dark-field (SDF) imaging in the rabbits during endotoxic shock after fluid resuscitation with different target mean arterial pressure (MAP), and evaluation of feasibility of monitoring small intestine villus microcirculation by SDF were studied. Sixty standard New Zealand white rabbits were randomly divided into two groups: low target MAP group (group A, n = 30) and high target MAP group (group B, n = 30). Fistula operation of ileum was made in vitro, and lipopolysaccharide (LPS, 2 mg/kg) was injected to establish endotoxic shock model. Group A was administered with the lower dose fluid resuscitation (lactated Ringer solution, 20 mL×kg-1×h-1) for target MAP of 65 mmHg (1 mmHg = 0.133 kPa); group B was administered with the higher dose fluid resuscitation (lactated Ringer solution, 30 mL×kg-1×h-1) for MAP of 80 mmHg. Continuous norepinephrine intravenous injection (0.5-1.0 μg×kg-1×min-1) was administered only after fluid therapy couldn't reach the target MAP. The changes of small intestine villus microcirculation perfusion indexes such as vessels per villus (VV), proportion of perfused villi (PPV), microvascular flow index (MFI), borders of villus score (BVS), vessels villus score (VVS) were continuously observed and recorded before the shock, during the shock and after fluid resuscitation using SDF imaging. The differences of microcirculation perfusion were compared between two groups using the specific parameter evaluation system to determine severity of villi microcirculation and injury scores at different stages. VV and borders of villus were clear and contact before shock in two groups. After shock, VV, PPV were significantly decreased in both two groups, the borders of villus were destroyed, MFI, BVS, VVS and the total score of villi injury microcirculation were obviously and severely decreased. Partial blood flow of villous capillaries after fluid resuscitation was recovered in two groups, but the perfusion of some region was un-balanced with the outworn borders of villus. VV were rose as compared before and after fluid resuscitation in groups A and B (vessels: 1.21±0.22 vs. 0.81±0.12, 1.54±0.28 vs. 0.79±0.13), and PPV [(31±4)% vs. (12±2)%, (38±5)% vs. (13±3)%], MFI (1.55±0.09 vs. 1.09±0.03, 1.97±0.11 vs. 1.05±0.03), VVS (points: 1.22±0.08 vs. 0.89±0.02, 2.06±0.15 vs. 0.90±0.02) and the sum of MFI, BVS, VVS (3.70±0.19 vs. 2.85±0.07, 5.01±0.29 vs. 2.88±0.08) were significant rose (all P < 0.05). The recovery of group B was better than that of group A, and the injury score was reduced. But BVS were not increased in both groups compared with before and after shock (points: 0.93±0.05 vs. 0.87±0.03, 0.98±0.09 vs. 0.93±0.05, both P > 0.05). For the small intestine villus microcirculation perfusion, the higher target MAP (80 mmHg) after fluid resuscitation or/and vasoconstrictor drugs usage were probably better than the relatively lower target MAP (65 mmHg) during endotoxic shock. SDF imaging is a very promising technique for intestinal villi microcirculatory visualization and assessment.

Effects of vasodilator and esmolol-induced hemodynamic stability on early post-operative cognitive dysfunction in elderly patients: a randomized trial.

To investigate the effect of continuous intravenous injection of nicardipine and/or nitroglycerin with or without esmolol on the occurrence of early post-operative cognitive dysfunction (POCD) in elderly patients. Elderly patients (n=340) who underwent radiofrequency ablation for atrial fibrillation were randomized into five groups: A, nicardipine; B nicardipine+esmolol; C, (nitroglycerin) group; D nitroglycerin+esmolol; E (control) groups. The hemodynamic parameters were recorded, and Mini Mental State Examination was used to assess cognitive function. At 30 min and 60 minutes after anesthesia and at the conclusion of surgery, the rate pressure product value was significantly lower in Groups B (10621.1±321.7, 10544.2±321.8, and 10701.3±325.5, respectively) and D (10807.4±351.1, 10784.3±360.3, and 10771.7±345.7, respectively) than in Group E (13217.1±377.6, 13203.5±357.3, and 13119.2±379.5, respectively). The heart rate was significantly higher in Groups A (104.1±10.3, 104.9±11.1, and 103.9±11.8, respectively) and C (103.7±11.3, 105.5±10.5, and 107.7±11.7, respectively) than in Group E (89.3±12.0, 88.5±11.5, and 85.5±11.6, respectively). The incidence of POCD was significantly lower in Groups A and B than in Groups C, D, and E. Univariate regression analysis showed that regimens in Groups A, B, and E and doses of propofol and fentanyl were risk factors for POCD. Multivariate logistic regression analysis revealed significant associations between the incidence of POCD and interventions in Groups A and B. Maintenance of stable intraoperative hemodynamics using nicardipine and nitroglycerin or their combinations with esmolol, especially nicardipine with esmolol, reduced the incidence of POCD in the elderly with potential cardiovascular diseases.

Safety and efficacy of lobaplatin combined with 5-fluorouracil as first-line induction chemotherapy followed by lobaplatin-radiotherapy in locally advanced nasopharyngeal carcinoma: preliminary results of a prospective phase II trial

BackgroundDue to improvements in imaging and radiological techniques as well as the use of chemotherapy, distant metastasis has become the predominant mode of treatment failure in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). Platinum-based systemic chemotherapy has shown survival benefits and is now the standard strategy for systemic therapy in patients with LA-NPC. Notably, the third-generation platinum reagent lobaplatin has shown anti-tumor effects in several solid tumors with lower incidences of gastrointestinal, hepatic and renal toxicity relative to other platinum drugs. However, the safety and efficacy of lobaplatin as a first-line regimen in patients with LA-NPC are undetermined.MethodsPatients with stage III–IVa-b NPC received lobaplatin at a dose of 30 mg/m2 on days 1 and 22 combined with a continuous 120-h intravenous injection of 5-fluorouracil at a dose of 4 g/m2 followed by lobaplatin at a dose of 50 mg/m2 on days 43 and 64 concomitant with intensity-modulated radiation therapy. Objective response rates and acute toxicity were assessed based on RECIST (1.1) and CTCAE v.3.0, respectively. Kaplan-Meier analysis was used to calculate survival rates.ResultsFifty-nine patients were enrolled, and 44 patients (74.6%) received allocated cycles of chemotherapy. The objective response rates were 88.1% (95% confidence interval [CI], 0.77 to 0.95) and 100% after induction chemotherapy (ICT) and concurrent chemoradiotherapy (CRT), respectively. With a median follow-up period of 44 months, the 3-year estimated progression-free survival and overall survival were 86.4% (95% CI, 69.8 to 98.8) and 94.9% (95% CI, 89.5 to 100), respectively. The most common grade 3–4 toxicities were neutropenia (8.5%) and thrombocytopenia (40.7%) after ICT and CRT, respectively.ConclusionLobaplatin combined with 5-fluorouracil followed by lobaplatin-RT treatment showed encouraging anti-tumor effects with tolerable toxicities in patients with LA-NPC. Randomized controlled trials of lobaplatin in patients with LA-NPC are warranted.Trial registrationThis trial was registered with the Chinese Clinical Trials Registry and approved on March 31st, 2012, number ChiCTR-ONC-12002060.

Controllable continuous sub-tenon drug delivery of dexamethasone disodium phosphate to ocular posterior segment in rabbit

Corticosteroids have been used for treatment of posterior segment eye diseases, but the delivery of drug to the posterior segments is still a problem to resolve. In our study, we explore the feasibility of Sub-tenon’s Controllable Continuous Drug Delivery to ocular posterior segment. Controllable continuous sub-tenon drug delivery (CCSDD) system, intravenous injections (IV) and sub-conjunctival injections (SC) were used to deliver dexamethasone disodium phosphate (DEXP) in rabbits, the dexamethasone concentration was measured in the ocular posterior segment tissue by Shimadzu LC-MS 2010 system at different time points in 24 h after first dose injection. Levels of dexamethasone were significantly higher at 12, 24 h in CCSDD than two other approaches, and at 3, 6 h in CCSDD than IV in vitreous body (p < 0.01); at 6, 12, 24 h in CCSDD than two other approaches, and at 1, 3 h in CCSDD than IV in retinal/choroidal compound (p < 0.01); at 3, 6, 12, 24 h in CCSDD than two other approaches, and at 1 h in CCSDD than IV in sclera (p < 0.05). The AUC0–24 in CCSDD group is higher than two other groups in all ocular posterior segment tissue. Our results demonstrated that dexamethasone concentration could be sustained moderately higher in the posterior segment by CCSDD than SC and IV, indicating that CCSDD might be a therapeutic alternative to treat a variety of intractable posterior segment diseases.

Factors Influencing the Accurate Administration of Peristaltic Finger Infusion Pumps Attached to Polyvinylchloride Infusion Sets Containing Tris(2-ethylhexyl) trimellitate.

An accurate continuous intravenous injection via a peristaltic finger infusion pump has been utilized at outpatient clinics recently. An infusion element designed for this pump is necessary for the accurate handling of the pump, and for proper use of this equipment, we need accurate information. Our experiments have shown that medication administration has occasionally been incomplete at the calculated input time when a peristaltic finger infusion pump has been used. In this paper, we have investigated the cause of the delay in the administration time and the effect of the attachment procedure using a combination of features from three kinds of such infusion pumps and five kinds of exclusive polyvinyl chloride (PVC) infusion sets, under various conditions. Our results suggest that the time required for complete administration was correlated to the input time when five kinds of PVC tubing without stretching were attached to three kinds of peristaltic finger infusion pumps (R(2)=0.9998-1.0000). However, when the PVC tubing was stretched 1-3 cm and was attached to the pump, the time required for complete administration of the solution was prolonged compared to the recommended listed input time (p<0.01-0.05, ANOVA, Tukey-Kramer multiple comparison). Therefore, we suggest that the procedure technique used by the medical staff and involving the infusion pump adversely prolonged the time required for completion of the administration of medication. In our opinion, pharmacists must provide information concerning not only the drugs, but also the medical devices used to the physicians and nurses.

The effect of hypertonic saline on notch signaling pathway in experimentally induced cerebral ischemic rats

Objective To explore whether hypertonic saline would partake in regulating Notch signaling in microglia in experimentally induced cerebral ischemic rats. Methods Male SD rats were randomly divided into sham group, cerebral ischemia group, normal saline group (NS group), 10% hypertonic saline group (10%HS group), the model of cerebral ischemia were established in all rats except the sham group by using middle cerebral artery occlusion (MCAO). After 2 hours of MCAO, the rats were through reperfusion for 24 h. In addition, rats in the normal saline group and 10% HS group were respectively treated with a continuous intravenous injection of normal saline (0.3 mL/h) and 10% HS (0.3 mL/h) by tail vein for 24 h. Immunofluorescence methods, RT-PCR and Western blot were used to detect the expression of Notch1 and intracellular Notch receptor domain (NICD). All data was analyzed by one-way analysis of variance (ANOVA), The intergroup comparisons were analyzed by the least-significant-difference (LSD) tests. Differences were considered statistically significant if P<0.05. Results Immunofluorescence showed that the expression of Notch1 and NICD were significantly increased in the microglia around peri-ischemia area in cerebral ischemia group and normal saline group compared to sham group; the expression of Notch1 and NICD in the microglia around peri-ischemia area were significantly reduced in 10% HS group compared to ischemia group and NS group. RT-PCR showed that the mRNA expression of Notch1 was significantly increased in ischemia group and NS group compared to sham group ( sham group: 1.000±0.076; ischemia group: 2.203±0.283; NS group: 1.616±0.185; P<0.01); however, it was significantly reduced in 10% HS group compared to ischemia group and NS group ( ischemia group: 2.203±0.283; NS group: 1.616±0.185; 10%HS group: 1.202±0.177; P<0.05). Western blot showed that the protein expression of Notch1 was significantly increased in ischemia group and NS group compared to sham group ( sham group: 0.290±0.079; ischemia group: 0.750±0.029; NS group: 0.765±0.182; P<0.01); but was significantly reduced in 10% HS group compared to ischemia group and NS group (ischemia group: 0.750±0.029; NS group: 0.765±0.182; 10%HS group: 0.390±0.195; P<0.05). The protein expression of NICD was significantly increased in ischemia group and NS group compared to sham group ( sham group: 0.401±0.196; ischemia group: 0.906±0.359; NS group: 0.847±0.153; P<0.01); but was significantly reduced in 10% HS group compared to ischemia group and NS group ( ischemia group: 0.906±0.359; NS group: 0.847±0.153; 10%HS group: 0.561±0.165; P<0.05). Conclusion Our results suggest that HS markedly suppresses Notch signaling in microglia around the ischemia tissue area in experimental induced cerebral ischemic rats. Key words: Hypertonic saline; Normal saline; Cerebral ischemia; Middle cerebral artery occlusion (MCAO); Microglia; Notch signaling; Notch1; Notch receptor domain (NICD)

Effect of salvianolic acid B on TNF-α induced cerebral microcirculatory changes in a micro-invasive mouse model

PurposeTo investigate the effects of salvianolic acid B (SAB) on tumor necrosis factor α (TNF-α) induced alterations of cerebral microcirculation with a bone-abrading model. MethodsThe influences of craniotomy model and bone-abrading model on cerebral microcirculation were compared. The bone-abrading method was used to detect the effects of intracerebroventricular application of 40 μg/kg·bw TNF-α on cerebral venular leakage of fluorescein isothiocyanate (FITC)-albulmin and the rolling and adhesion of leukocytes on venules with fluorescence tracer rhodamine 6G. The therapeutical effects of SAB on TNF-α induced microcirculatory alteration were observed, with continuous intravenous injection of 5 mg/kg·h SAB starting at 20 min before or 20 min after TNF-α administration, respectively. The expressions of CD11b/CD18 and CD62L in leukocytes were measured with flow cytometry. Immunohistochemical staining was also used to detect E-selectin and ICAM-1 expression in endothelial cells. ResultsCompared with craniotomy method, the bone-abrading method preserved a higher erythrocyte velocity in cerebral venules and more opening capillaries. TNF-α intervention only caused responses of vascular hyperpermeability and leukocyte rolling on venular walls, without leukocyte adhesion and other hemodynamic changes. Pre- or post-SAB treatment attenuated those responses and suppressed the enhanced expressions of CD11b/CD18 and CD62L in leukocytes and E-selectin and ICAM-1 in endothelial cells induced by TNF-α. ConclusionsThe pre- and post-applications of SAB during TNF-α stimulation could suppress adhesive molecular expression and subsequently attenuate the increase of cerebral vascular permeability and leukocyte rolling.

Intravenous injection of l-BMAA induces a rat model with comprehensive characteristics of amyotrophic lateral sclerosis/Parkinson-dementia complex.

Non-protein amino acid beta-N-methylamino-l-alanine (l-BMAA) is a neurotoxin that was associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinson-Dementia Complex (ALS/PDC) in Guam. This neurotoxin has been implicated as a potential environmental factor in amyotrophic lateral sclerosis, Alzheimer's disease and other neurodegenerative diseases, and was found to accumulate in brain tissues of ALS/PDC patients. It is extremely important to establish a reliable animal model that has the comprehensive characteristics of ALS/PDC for studying mechanisms underlying neurodegeneration, and exploring effective therapies. However, very few good animal models that mimic ALS/PDC have been established. In this study, an ideal rat model that mimicked most characteristics of ALS/PDC was established by administering continuous intravenous (i.v.) injections of neurotoxic l-BMAA. Based on the data obtained, it was demonstrated that continuous i.v. injections of l-BMAA induced mitochondrial morphology and structural changes, astrogliosis, motor neuronal death, and other relative functional changes, which led to the overexpression of pro-inflammatory cytokines cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB) and tumor necrosis factor-alpha (TNF-α), and resulted in the upregulation of glycogen synthase kinase-3 (GSK3), downregulation of astrocytic glutamate transporter-1 (GLT-1), accumulation of microtubule-associated protein tau and cytosolic aggregates of TAR DNA-binding protein-43 (TDP-43) in degenerating motor neurons. These results suggest that this model could be used as a useful tool for the mechanistic and therapeutic study of ALS/PDC.

Cornin increases angiogenesis and improves functional recovery after stroke via the Ang1/Tie2 axis and the Wnt/β-catenin pathway.

We investigated whether cornin, an iridoid glycoside isolated from fruits of Verbena officinalis L., regulated angiogenesis and thereby improved functional outcomes after stroke and discovered a potential mechanism. The effects of cornin on proliferation of rat artery smooth muscle cell (RASMC) and signalling was investigated in vitro. Adult male rats were subjected to 1h of middle cerebral artery occlusion (MCAO) and reperfusion and treated with or without 25mg/kg of cornin, starting 24h after ischemia and reperfusion, by continuous intravenous injection daily for 14days. Neurological functional tests were performed and cerebral Evans blue extravasation was measured. Angiogenesis and angiogenic factor expressions were measured by immunohistochemistry and Western blotting, respectively. Cornin increased the proliferation of RASMC and enhanced the expression of Wnt5a, β-catenin, cyclin D1 and angiopoietin-1 (Ang1). Cornin treatment promoted angiogenesis in the ischemic brain core and improved functional outcomes after stroke. Cornin-treated MCAO rats showed significant increase in vascularization and expression of vascular endothelial growth factor and Ang1 and phosphorylation of Tie2 and Akt compared with vehicle-treated MCAO rats. The Ang1/Tie2 axis and Wnt/β-catenin pathways appear to mediate cornin-induced angiogenesis.

Application of the ERK signaling pathway inhibitor PD98059 in long-term in vivo experiments.

The aim of this study was to explore methods by which the ERK signaling pathway inhibitor PD98059 (PD) could be used in long-term in vivo experiments. Forty healthy New Zealand rabbits were randomly divided into blank control, model control, PD low-dose, PD high-dose, PD blank, dimethyl sulfoxide (DMSO) control, DMSO blank, and positive control groups. The corresponding treatments were administered to each experimental group over the course of four weeks, after which, total ERK1/2 and ERK5 protein levels, protein phosphorylation, and gene expression were measured in myocardial tissues. Treatment of rabbits with Adriamycin (doxorubicin) resulted in the significant overall differences in ERK1/2 and ERK5 phosphorylation (P < 0.05). Compared with the model control group, changes in phosphorylated ERK1/2 and phosphorylated ERK5 were lowest in the PD high-dose group (P < 0.05). No significant differences in total protein and mRNA levels of myocardial ERK1/2 and ERK5 were detected between the groups after four weeks (P > 0.05). Continuous intravenous injection of PD98059 significantly reduced phosphorylation of ERK1/2 and that of ERK5. In conclusion, Adriamycin-induced myocardiopathy and abnormal ERK signaling might constitute a valuable model foruse in long-term experiments. These methods may provide a theoretical basis for related in vivo studies of long duration.