Pantoprazole (PPZ) Inhibits RANKL-Induced Osteoclast Formation and Function In Vitro and Prevents Lipopolysaccharide- (LPS-) Induced Inflammatory Calvarial Bone Loss In Vivo.

Bone remodeling is a process delicately balanced between osteoclastic bone resorption and osteoblastic bone formation. Osteoclasts (OCs) are multinucleated giant cells formed through the fusion of monocytic precursors of the hematopoietic stem cells lineage. OCs are the exclusive cells responsible for the resorption and degradation of the mineralized bone matrix. Pantoprazole (PPZ), a proton pump inhibitor (PPI), is commonly prescribed to reduce excess gastric acid production for conditions such as gastroesophageal reflux disease and peptic ulcer disease. Studies have found contradictory effects of PPI therapy on bone metabolism due to the lack of understanding of the exact underlying mechanism. In this study, we found that PPZ inhibits receptor activator of nuclear factor-κB (NF-κB) ligand- (RANKL-) induced osteoclastogenesis from bone marrow monocytic/macrophage (BMMs) precursors and the bone-resorbing activity of mature OCs. Correspondingly, the expression of OC marker genes was also attenuated. At the molecular level, PPZ treatment was associated with reduced activation of the ERK MAPK signaling pathways crucial to OC differentiation. Additionally, the in vivo administration of PPZ protected mice against lipopolysaccharide- (LPS-) induced inflammatory calvarial bone erosion, as a result of the reduced number and activity of OCs on the calvarial bone surface. Although PPI use is associated with increased risk of osteoporosis and bone fractures, our study provides evidence for the direct inhibitory effect of PPZ on OC formation and bone resorption in vitro and in vivo, suggesting a potential therapeutic use of PPZ in the treatment of osteolytic disease with localized bone destruction.

Stability study of dezocine in 0.9% sodium chloride solutions for patient-controlled analgesia administration.

BACKGROUND: Dezocine, a mixed agonist/antagonist of opioid receptors, has been used in iv patient-controlled analgesia (PCA) pumps for postoperative pain control. The aim of this study was to investigate the physicochemical stability of dezocine solutions in 0.9% sodium chloride for injection for PCA administration. METHODS: Solutions of dezocine (0.3, 0.45, or 0.6 mg/mL in 0.9% sodium chloride for injection) were stored in polyolefin bags and glass bottles. Their stabilities at storage conditions of 4°C for 14 days and 25°C for 72 hours were studied. For all preparations, physical characteristics (including pH, color, and presence of precipitates) were evaluated. Each preparation of dezocine was also analyzed using a stability-indicating high-performance liquid chromatography method. A solution was considered stable if it maintained at least 90% of its initial concentration. RESULTS: No notable changes in pH, color, or precipitation were observed in any of the prepared solutions over the testing period. All formulations maintained >97% of the initial dezocine concentration under the storage conditions evaluated. CONCLUSIONS: Dezocine solutions at 0.3, 0.45, or 0.6 mg/mL in 0.9% sodium chloride for PCA administration were stable for 72 hours at 25°C and for 14 days at 4°C when packaged in polyolefin bags or glass bottles and protected from light.

DEPDC1 promotes cell proliferation and tumor growth via activation of E2F signaling in prostate cancer.

DEP domain containing 1 (DEPDC1) is recently reported to be overexpressed in several types of human cancer; however the role of DEPDC1 in prostate cancer remains to be investigated. Herein, we identified that the DEPDC1 mRNA and protein expression levels were dramatically increased in prostate cancer tissues and cell lines. Overexpression of DEPDC1 promoted, but depletion of DEPDC1 inhibited cell proliferation by regulating the G1-S phase cell cycle transition. Importantly, we found that DEPDC1 was essential for the tumor growth and formation of bone metastases of prostate cancer cells in vivo. Finally, we demonstrated that DEPDC1 interacted with E2F1 and increased its transcriptional activity, leading to hyper-activation of E2F signaling in prostate cancer cells. Our findings reveal an oncogenic role of DEPDC1 in prostate cancer progression via activation of E2F signaling, and suggest DEPDC1 might be a potential therapeutic target against the disease.

Intraoperative contrast-enhanced ultrasonography for microcirculatory evaluation in rhesus monkey with spinal cord injury.

This study tried to quantify spinal cord perfusion by using contrast-enhanced ultrasound (CEUS) in rhesus monkey models with acute spinal cord injury. Acute spinal cord perfusion after injury was detected by CEUS, coupling with conventional ultrasound (US) and Color Doppler US (CDFI). Time-intensity curves and perfusion parameters were obtained by autotracking contrast quantification (ACQ) software in the epicenter and adjacent regions of injury, respectively. Neurological and histological examinations were performed to confirm the severity of injury. US revealed spinal cords were hypoechoic and homogeneous, whereas dura maters, pia maters, and cerebral aqueducts were hyperechoic. After spinal cord contusion, the injured spinal cord was hyperechoic on US, and intramedullary vessels of adjacent region of injury were increased and dilated on CDFI. On CEUS hypoperfusion were found in the epicenter of injury, while hyperperfusion in its adjacent region. Quantitative analysis showed that peak intensity (PI) decreased in epicenters of injury but significantly increased in adjacent regions at all time points (p < 0.05). Functional evaluation demonstrated significant deterioration compared to pre-contusion (p < 0.05). Quantitative analysis with CEUS is a promising method for monitoring perfusion changes of spinal cord injury in overall views and real-time.

Simultaneous Determination of Dexamethasone, Ondansetron, Granisetron, Tropisetron, and Azasetron in Infusion Samples by HPLC with DAD Detection.

A simple and rapid high-performance liquid chromatography with diode array detector (HPLC-DAD) method has been developed and validated for simultaneous quantification of five antiemetic agents in infusion samples: dexamethasone, ondansetron, granisetron, tropisetron, and azasetron. The chromatographic separation was achieved on a Phenomenex C18 column (4.6 mm × 150 mm, 5 µm) using acetonitrile-50 mM KH2PO4 buffer-triethylamine (25 : 74 : 1; v/v; pH 4.0). Flow rate was 1.0 mL/min with a column temperature of 30°C. Validation of the method was made in terms of specificity, linearity, accuracy, and intra- and interday precision, as well as quantification and detection limits. The developed method can be used in the laboratory to routinely quantify dexamethasone, ondansetron, granisetron, tropisetron, and azasetron simultaneously and to evaluate the physicochemical stability of referred drugs in mixtures for endovenous use.

Meta-analysis of the effects of oral and intravenous dexamethasone premedication in the prevention of paclitaxel-induced allergic reactions.

BACKGROUND: Dexamethasone premedication is required to prevent paclitaxel-related hypersensitivity reactions (HSRs). Oral dexamethasone (PO-D) has been considered the standard premedication regimen. However, whether intravenous dexamethasone (IV-D) is feasible for preventing paclitaxel-related HSRs is still unclear. We conducted a meta-analysis to compare these two regimens. METHODS: We performed a systematic search in the PubMed, China National Knowledge Infrastructure, and Web of Science databases for relevant articles published before June 2016. Outcomes included HSRs and severe HSRs. Statistical analyses were performed using RevMan 5.2 software. RESULT: Six studies comprising 1347 patients were included in the meta-analysis. The PO-D premedication regimen showed a significantly decreased incidence of severe HSRs compared with the IV-D regimen with an OR of 0.53 (95% CI 0.28-0.99, p = 0.05). However, there was no difference in the overall paclitaxel-related HSR rates between the two premedication regimens (OR 0.76, 95% CI 0.55-1.06, p = 0.11). Subgroup analyses according to study type and country of origin showed similar statistical results between the two premedication regimens. CONCLUSION: Our meta-analysis showed that the PO-D premedication regimen is superior to the IV-D regimen in preventing paclitaxel-related HSRs. Additional randomized controlled trials are needed to confirm our findings.

Stability of azasetron-dexamethasone mixture for chemotherapy-induced nausea and vomiting administration.

Combination antiemetic therapy has become common practice for the prevention of nausea and vomiting caused by anticancer drugs. In this study, we investigated the stability of azasetron hydrochloride 0.1 mg/mL plus dexamethasone sodium phosphate 0.05, 0.1, or 0.2 mg/mL in 0.9% sodium chloride injection and stored in polyolefin bags and glass bottles over a period of 14 days at 4°C and 48 hours at 25°C. The stability studies were evaluated by visual inspection, pH measurement, and a high-pressure liquid chromatography assay of drug concentrations. During the study period, the concentration of each drug in the various solutions remained above 97% of the initial concentration at both 4°C and 25°C when protected from room light. Under the condition of 25°C with exposure to room light, the concentrations of both drugs were significantly lowered over 48 hours. The pH value decreased, and the color changed from colorless to pink. Our study demonstrates that the azasetron-dexamethasone mixture at a clinically relevant concentration seems to be stable for 48 hours at 25°C and for 14 days at 4°C when packaged in polyolefin bags or glass bottles and protected from room light. The room light is the main influential factor on stability. Clinicians should be aware that combinations of azasetron hydrochloride and dexamethasone sodium phosphate in solution with light exposure should be avoided.

Incompatibilities of lornoxicam with 4 antiemetic medications in polyolefin bags during simulated intravenous administration.

The administration of drugs by patient-controlled analgesia (PCA) is routinely practiced for the management of postoperative pain. It is common for 2 or more drugs to be combined in PCA solutions. The combination of analgesics and antiemetic agents is frequently required. Unfortunately, the compatibility and stability of lornoxicam and antiemetic agents, such as droperidol, ondansetrone, granisetron, and tropisetron, has not been determined. The aim of this study was to evaluate the compatibility and stability of solutions containing lornoxicam with the 4 antiemetic agents in combination for PCA administration.In our study, test samples were prepared in triplicate by adding 40 mg lornoxicam and 5 mg droperidol, 8 mg ondansetron, 6 mg granisetron, or 5 mg tropisetron to 100-mL polyolefin bags of sodium chloride 0.9% and stored at 25 °C. The analgesic mixture samples were visually inspected for precipitation, cloudiness, and discoloration at each sampling interval. Drug concentrations were determined using high-performance liquid chromatographic (HPLC) analysis.No loss of lornoxicam occurred with any of the 4 antiemetic agents tested for up to 48 hours. However, the contents of droperidol, ondansetron, granisetron, and tropisetron were significant loss >48 hours. After storage of 4.0 to 48.0 hours, the presence of a slight precipitate was observed in all the injection combinations.The results indicate that combinations of lornoxicam with droperidol, ondansetrone, granisetron, or tropisetron in infusion solution during simulated intravenous PCA administration were incompatibility when stored protected from light at 25 °C.

Stability of tramadol with three 5-HT3 receptor antagonists in polyolefin bags for patient-controlled delivery systems.

BACKGROUND: Mixing 5-hydroxytryptamine-3 (5-HT3) receptor antagonists with patient-controlled analgesia (PCA) solutions of tramadol has been shown to decrease the incidence of nausea and vomiting associated with the use of tramadol PCA for postoperative pain. However, such mixtures are not commercially available, and the stability of the drug combinations has not been duly studied. The study aimed to evaluate the stability of tramadol with three 5-HT3 receptor antagonists in 0.9% sodium chloride injection for PCA administration. MATERIALS AND METHODS: Test samples were prepared by adding 1,000 mg tramadol hydrochloride, 8 mg ondansetron hydrochloride, and 6 mg granisetron hydrochloride or 5 mg tropisetron hydrochloride to 100 mL of 0.9% sodium chloride injection in polyolefin bags. The samples were prepared in triplicates, stored at either 25°C or 4°C for 14 days, and assessed using the following compatibility parameters: precipitation, cloudiness, discoloration, and pH. Chemical stability was also determined using a validated high-pressure liquid chromatography method. RESULTS: All of the mixtures were clear and colorless throughout the initial observation period. No change in the concentration of tramadol hydrochloride occurred with any of the 5-HT3 receptor antagonists during the 14 days. Similarly, little or no loss of the 5-HT3 receptor antagonists occurred over the 14-day period. CONCLUSION: Our results suggest that mixtures of tramadol hydrochloride, ondansetron hydrochloride, granisetron hydrochloride, or tropisetron hydrochloride in 0.9% sodium chloride injection were physically and chemically stable for 14 days when stored in polyolefin bags at both 4°C and 25°C.

Compatibility of butorphanol with granisetron in 0.9% sodium chloride injection packaged in glass bottles or polyolefin bags.

PURPOSE: The stability of admixtures containing butorphanol and granisetron in polyolefin bags and glass bottles stored at 4 and 25 °C was studied. METHODS: Commercial solutions of butorphanol tartrate and granisetron hydrochloride were combined and further diluted with 0.9% sodium chloride injection to final concentrations of butorphanol tartrate 0.08 mg/mL and granisetron 0.03 or 0.06 mg/mL; the resulting mixtures were packaged in polyolefin bags and glass bottles. The admixtures were assessed for periods of up to 48 hours after storage at 25 °C without protection from room light and up to 14 days at 4 °C with protection from room light. The chemical stability of the admixtures was evaluated by a validated high-performance liquid chromatography (HPLC) method and by measurement of pH values. Solution appearance and color were assessed by observing the samples against room light and dark backgrounds. RESULTS: HPLC analysis demonstrated that the percentages of the initial concentrations of butorphanol and granisetron in the various solutions remained above 97% during the testing period. No changes in color or turbidity were observed in any of the prepared solutions. Throughout this period, pH values remained stable. CONCLUSION: Admixtures of butorphanol tartrate 0.08 mg/mL and granisetron 0.03 or 0.06 mg/mL in 0.9% sodium chloride injection in polyolefin bags or glass bottles remained stable for 48 hours when stored at 25 °C exposed to room light and for 14 days when stored at 4 °C protected from room light.

Stability of butorphanol-tropisetron mixtures in 0.9% sodium chloride injection for patient-controlled analgesia use.

Tropisetron is an adjuvant for butorphanol used in intravenous patient-controlled analgesia (PCA) and has been reported to provide superior pain control. It is efficacious in reducing the incidence of postoperative nausea and vomiting. However, this admixture is not available commercially and stability data applicable to hospital practice are limited. This study aimed to describe the drug compounding and evaluates the long-term (up to 14 days) stability of butorphanol and tropisetron in 0.9% sodium chloride injection for PCA use.In this study, commercial solutions of butorphanol tartrate and tropisetron hydrochloride were combined and further diluted with 0.9% sodium chloride injection to final concentrations of butorphanol tartrate 0.08 mg/mL and tropisetron hydrochloride 0.05 mg/mL. The polyolefin bags and glass bottles were stored at 4°C and 25°C for up to 14 days. The drug stabilities were determined by visual inspection, pH measurement, and high-pressure liquid chromatography assay of drug concentrations.The data obtained for admixtures prepared and stored at temperatures of 25°C and 4°C show the drugs have maintained at least 98% of the initial concentration. All solutions remained clear and colorless over the 14-day period, and the pH value did not change significantly.The results indicate that admixtures of butorphanol tartrate 0.08 mg/mL and tropisetron hydrochloride 0.05 mg/mL in 0.9% sodium chloride injection solution were stable for 14 days when stored in polyolefin bags or glass bottles at 4°C and 25°C and protected from light. The infusion is feasible for manufacturing in pharmacy aseptic units and can be stored for up to 14 days for routine use in PCA infusions.

Effects of recombinant human interleukin-10 on Treg cells, IL-10 and TGF-ß in transplantation of rabbit skin.

The current study aimed to investigate the rejection and survival time of grafted skin, and the changes of Treg cells, interleukin 10 (IL-10) and transforming growth factor-ß (TGF-ß) in peripheral blood following skin transplantation with recombinant human interleukin-10 (rhIL-10) or cyclosporin A (CsA), as well as the role of IL-10 in immunological rejection mechanisms. A total of 36 rabbits were divided into two groups. The skin of a donor rabbit was transplanted onto the back of one receptor rabbit. Receptors were randomly divided into six groups, including rhIL-10 low-dose (5 µg/kg/d), rhIL-10 high-dose (10 µg/kg/d), CsA low-dose (5 mg/kg/d), CsA high-dose (10 mg/kg/d), rhIL-10 (5 µg/kg/d) and CsA (5 mg/kg/d) and negative control normal saline (NS; 1 ml/d). All groups received intramuscular drug injection for ten days, beginning one day prior to skin transplantation surgery. Following transplantation, each rabbit's peripheral blood was collected at different times. The changes of CD4+CD25+ regulatory T cells, IL-10 and TGF-ß were determined by flow cytometry and enzyme-linked immunosorbent assay. When compared with the control group, the rejection and survival times of the experimental groups were longer following skin graft. Compared with the two CsA groups and the control group, the proportion of CD4+CD25+ regulatory T cells of rhIL-10 groups was significantly upregulated on the 4th and 7th days following surgery. However, TGF-ß levels were not significantly different. Data suggested that the concentration of IL-10 was positively correlated with the proportion of CD4+CD25+ regulatory T cells. In addition, IL-10 may delay the rejection time of rabbit skin transplantation and prolong the survival time. Thus, the role of IL-10 in inhibited allograft rejection may be associated with CD4+CD25+ regulatory T cells and IL-10, and may be independent of TGF-ß.

Compatibility of butorphanol and droperidol in 0.9% sodium chloride injection.

PURPOSE: The compatibility and stability of butorphanol tartrate and droperidol in polyvinyl chloride (PVC) bags and glass bottles stored at 4°C and 25°C for up to 15 days were studied. METHODS: Admixtures were assessed initially and for 15 days after preparation in PVC bags and glass bottles using 0.9% sodium chloride injection as a diluent and stored at 4°C and 25°C. The initial drug concentrations were 0.08 mg/mL for butorphanol tartrate and 0.05 mg/mL for droperidol. Samples were withdrawn from each container immediately after preparation and at predetermined intervals (2, 4, 8, 24, 48, 72, 120, 168, 240, and 360 hours after preparation). The solutions were visually inspected for precipitation, cloudiness, and discoloration at each sampling interval. Drug concentrations were determined using a validated high-pressure liquid chromatography method. RESULTS: After 15 days of storage, all formulations tested retained >98% of the initial concentrations of both drugs. The drug mixtures were clear in appearance, and no color change or precipitation was observed. Throughout this period, pH values remained stable. CONCLUSION: Admixtures of butorphanol tartrate 0.08 mg/mL and droperidol 0.05 mg/mL in 0.9% sodium chloride injection were stable for at least 360 hours when stored in PVC bags or glass bottles at 4°C and 25°C and protected from light.

[Study on yohimbine in positive mode by ion trap mass spectrometry].

OBJECTIVE: The structure and fragmentation pathway of yohimbine were elucidated by electron spray ionization mass spectrometry( ESI-MS). METHODS: Quasi-molecular ion peak m/z 355 [M + H]+ was detected by ESI-MS, and the main fragment ions of m/z 212 and m/z 144 were detected by ESI-MS2. RESULTS: There are two main fragment pathway for m/z 355 [M + H]+ by ESI-MS2 and the fragment broken in pyridine ring. The full scan MS3 spectra of fragment m/z 212, and m/z 144 was obtained by ion trap mass spectrometry. The characteristic fragmentation was used to prove the structure of m/z 212, and m/z 144. The fragment routes of characteristic were discussed on the basis of ESI mass spectra. CONCLUSION: It can provide the experimental data for studying pharmacokinetics in vivo and modifying structure.