Synthesis of Substituted of Benzo[4,5]imidazo[1,2-a]pyrimidines through (3 + 2+1) Cyclization of 2-Aminobenzimidazole, Acetophenone, and N,N-Dimethylformamide as One-Carbon Synthon.

An efficient method for the construction of benzo[4,5]imidazo[1,2-a]pyrimidines using N,N-dimethylformamide as a one-carbon source and 2-aminobenzimidazoles and acetophenone as substrates through a one-pot, three-component cascade reaction is described. Spectra investigations indicated the fluorescent properties of selected products, exhibiting quantum yields 0.07-0.16 with maxima absorption at 266-294 nm and emission at 472-546 nm.

A rapid construction of new boron heterocycles and evaluation of photophysical properties of iminoboronates.

A green and efficient method for the synthesis of oxadiazaborole, dioxazaborinine, and oxadiazaborinine from the reactions of phenylboronic acid with amidoxime, α-hydroxyl oxime and α-hydroxyl hydrazone, respectively, is described. The reactions were performed under catalyst-free and mild conditions. All products can be rapidly purified by filtration and washing. In addition, a set of iminoboronates were prepared following a one-pot multicomponent reaction procedure using α-hydroxyl hydrazone, salicylaldehyde and boronic acid derivatives as starting materials and their photophysical properties were assessed. Then, cross-coupling reactions can be carried out smoothly on some target compounds, which may help develop new boron masking strategies.

High Levels of LINC01140 Expression Predict a Good Prognosis and Improve Radiotherapy in Sarcoma Patients.

Long intergenic non-protein coding RNA has an important biological role in tumors. But, LINC01140 in sarcoma has not been studied yet. This study investigates the expression and prognosis role of LINC01140 in sarcoma. LINC01140 was lower in metastatic sarcoma, and low LINC01140 expression predicted poor overall survival, disease-free survival, and disease-specific survival in sarcoma. High LINC01140 expression and radiotherapy could promote survival of sarcoma. Gene set enrichment analysis showed LINC01140 was involved in interferon-gamma response, epithelial-mesenchymal transition, the interaction between cytokine receptors, and cholesterol homeostasis. Gene ontology enrichment analysis showed LINC01140 was involved in immunity, fatty acid metabolism, amino acid metabolism, cell division, serine/threonine-protein kinase. LINC01140 expression was negatively correlated with various epithelial-mesenchymal transition factors and positively correlated with the expression of anti-cancer factor hypermethylated-in-cancer 1. These results confirmed that LINC01140 may be a potential novel prognostic molecule in sarcoma.

H2S exposure induces cell death in the broiler thymus via the ROS-initiated JNK/MST1/FOXO1 pathway.

Hydrogen sulfide (H2S) is a common toxic gas in chicken houses that endangers the health of poultry. Harbin has a cold climate in winter, and the conflict between heat preservation and ventilation in poultry houses is obvious. In this study, we investigated the H2S content in chicken houses during winter in Harbin and found that the H2S concentration exceeded the national standard in individual chicken houses. Then, a model of H2S exposure was established in an environmental simulation chamber. We also developed a NaHS exposure model of chicken peripheral blood lymphocytes in vitro. Proteomics analysis was used to reveal the toxicology of thymus injury in broilers, the FOXO signaling pathway was determined to be significantly enriched, ROS bursts and JNK/MST1/FOXO1 pathway activation induced by H2S exposure were detected, and ROS played an important switch role in the JNK/MST1/FOXO1 pathway. In addition, H2S exposure-induced thymus cell death involved immune dysregulation. Overall, the present study adds data for H2S contents in chicken houses, provides new findings for the mechanism of H2S poisoning and reveals a new regulatory pathway in immune injury.

microRNA-33-3p involved in selenium deficiency-induced apoptosis via targeting ADAM10 in the chicken kidney.

Selenium (Se) deficiency induces typical clinical and pathological changes and causes various pathological responses at the molecular level in several different chicken organs; the kidney is one of the target organs of Se deficiency. To explore the mechanisms that underlie the effects of microRNA-33-3p (miR-33-3p) on Se deficiency-induced kidney apoptosis, 60 chickens were randomly divided into two groups (30 chickens per group). We found that Se deficiency increased the expression of miR-33-3p in the chicken kidney. A disintegrin and metalloprotease domain 10 (ADAM10) was verified to be a target of miR-33-3p in the chicken kidney. The overexpression of miR-33-3p decreased the expression levels of ß-catenin, cyclinD1, T-cell factor (TCF), c-myc, survivin, and Bcl-2; it increased the expression levels of E-cadherin, Bak, Bax, and caspase-3; and it increased the number of chicken kidney cells in the G0/G1 phase. In addition, Se deficiency caused the ultrastructure of the kidney to develop apoptotic characteristics. The results of flow cytometry analysis and AO/EB staining showed that the number of apoptotic chicken kidney cells increased in the miR-33-3p mimic group. All these results suggest that Se deficiency-induced cell cycle arrest and apoptosis in vivo and in vitro in the chicken kidney via the regulation of miR-33-3p, which targets ADAM10.

Dexmedetomidine improves acute stress-induced liver injury in rats by regulating MKP-1, inhibiting NF-κB pathway and cell apoptosis.

Acute stress is a frequent and unpredictable disease for many animals. Stress is widely considered to affect liver function. However, the underlying mechanism by which dexmedetomidine (DEX) attenuates acute stress-induced liver injury in rats remains unclear. In this study, we used forced swimming for 15 min and acute 3-hr restraint stress model. Behavioral tests and changes in norepinephrine levels confirmed the successful establishment of the acute stress model. Acute stress-induced liver injury, evidenced by hematoxylin and eosin-stained pathological sections and increased serum aminotransferase and aspartate aminotransferase levels, was reduced in DEX-treated livers. Reactive oxygen species and oxidative stress levels were dramatically decreased with DEX treatment compared with acute stress-induced liver injury. DEX significantly reduced acute stress-induced liver inflammation and apoptosis, as assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and inflammation and apoptosis-related protein levels. DEX treatment also effectively inhibited acute stress-induced c-Jun N-terminal kinase (JNK), P38, and BAD signaling pathway activation, and significantly induced MKP-1 activation. Thus, DEX has a protective effect on acute-stress-induced liver injury by reducing inflammation and apoptosis, which suggests a potential clinical application for DEX in stress syndrome.

Dexmedetomidine alleviates lipopolysaccharide-induced acute kidney injury by inhibiting the NLRP3 inflammasome activation via regulating the TLR4/NOX4/NF-κB pathway.

Dexmedetomidine (DEX) prevents kidney damage caused by sepsis, but the mechanism of this effect remains unclear. In this study, the protective molecular mechanism of DEX in lipopolysaccharide (LPS)-induced acute kidney injury was investigated and its potential pharmacological targets from the perspective of inhibiting oxidative stress damage and the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation. Intraperitoneal injection of DEX (30 µg/kg) significantly improved LPS (10 mg/kg) induced renal pathological damage and renal dysfunction. DEX also ameliorated oxidative stress damage by reducing the contents of reactive oxygen species, malondialdehyde and hydrogen peroxide, and increasing the level of glutathione, as well as the activity of superoxide dismutase and catalase. In addition, DEX prevented nuclear factor-kappa B (NF-κB) activation and I-kappa B (IκB) phosphorylation, as well as the expressions of NLRP3 inflammasome-associated protein and downstream IL-18 and IL-1ß. The messengerRNA (mRNA) and protein expressions of toll-like receptor 4 (TLR4), NADPH oxidase-4 (NOX4), NF-κB, and NLRP3 were also significantly reduced by DEX. Their expressions were further evaluated by immunohistochemistry, yielding results were consistent with the results of mRNA and protein detection. Interestingly, the protective effects of DEX were reversed by atipamezole-an alpha 2 adrenal receptor (α2 AR) inhibitor, whereas idazoxan-an imidazoline receptor (IR) inhibitor failed to reverse this change. In conclusion, DEX attenuated LPS-induced AKI by inhibiting oxidative stress damage and NLRP3 inflammasome activation via regulating the TLR4/NOX4/NF-κB pathway, mainly acting on the α2 AR rather than IR.

Dexmedetomidine attenuates lipopolysaccharide-induced liver oxidative stress and cell apoptosis in rats by increasing GSK-3ß/MKP-1/Nrf2 pathway activity via the α2 adrenergic receptor.

Dexmedetomidine (DEX) protects against liver damage caused by sepsis. The purpose of this study was to confirm the regulatory effects of DEX on glycogen synthase kinase 3 beta (GSK-3ß) via the α2 adrenergic receptor (α2AR) and evaluate the role of GSK-3ß in lipopolysaccharide (LPS)-induced liver injury. Sprague-Dawley (SD) rats were administered an intraperitoneal injection of DEX (30 µg/kg) 30 min before an intraperitoneal injection of LPS (10 mg/kg). HE staining and serum biochemical test results indicated that DEX significantly improved liver histopathological damage and liver function indices. Furthermore, DEX increased super oxide dismutase (SOD) activity and L-glutathione (GSH) levels, and inhibited malondialdehyde (MDA) production. Western blot (WB) analysis demonstrated that treatment with the GSK-3ß inhibitor SB216763 increased antioxidant-related protein mitogen-activated protein kinase phosphatase 1 (MKP-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) expression. In addition, anti-apoptosis-related proteins were up-regulated and pro-apoptosis-related proteins were down-regulated by SB21676 administration. WB analysis also showed that DEX increased anti-apoptosis-related protein levels and decreased pro-apoptotic protein levels in LPS-induced liver injury. Nrf2, p53, and activated caspase-3 levels were further evaluated using immunohistochemistry (IHC), producing results consistent with WB results. The α2AR antagonist atipamezole (AT) significantly reversed the protective effects of DEX, as shown by WB analysis. Our data suggested that α2AR plays an important role in reversing the effects of liver oxidative stress and apoptosis via DEX, and that DEX exerts antioxidant and anti-apoptosis effects through regulation of the GSK-3ß/MKP-1/Nrf2 pathway.

Hydrogen sulfide-induced oxidative stress leads to excessive mitochondrial fission to activate apoptosis in broiler myocardia.

Hydrogen sulfide (H2S), as an environmental gas pollutant, has harmful effects on many tissues and organs, including myocardium. However, the underlying mechanisms of H2S-induced myocardia toxicity remain poorly understood. The present study was designed to investigate the effect of H2S on myocardia injury in broilers from the perspective of apoptosis. 30 ppm H2S was administered in the broiler chamber for 2, 4 and 6 week, respectively, and the myocardial samples in control groups and H2S groups were collected immediately after euthanized broilers. Transmission electron microscope, test kits, qRT-PCR and western blot were performed. Results showed that H2S exposure decreased the activities of catalase (CAT) and total antioxidant capability (T-AOC), whereas the content of hydrogen peroxide (H2O2) and the activity of inducible nitric oxide synthase (iNOS) enhanced. Besides, we found the excessive expression of mitochondrial fission genes (Drp1 and Mff) by H2S, the dynamic balance of mitochondrial fission and fusion is destroyed. Furthermore, the levels of pro-apoptotic gene (including CytC, Cas3, Cas8, Cas9, TNF-α and Bax) increased after H2S exposure, as well as the expression level of anti-apoptotic gene bcl-2 decreased. At the same time, the activities of ATPase (including Na+-K+-ATPase, Ca2+-ATPase, Mg2+-ATPase and Ca2+-Mg2+-ATPase) weakened under H2S exposure. Therefore, we conclude that H2S induced oxidative stress and then leaded to excessive mitochondrial fission, which involved in apoptosis and damage broiler myocardia.

MiR-128-1-5p regulates tight junction induced by selenium deficiency via targeting cell adhesion molecule 1 in broilers vein endothelial cells.

Vein endothelial cells (VECs) constitute an important barrier for macromolecules and circulating cells from the blood to the tissues, stabilizing the colloid osmotic pressure of the blood, regulating the vascular tone, and rapidly changing the intercellular connection, and maintaining normal physiological function. Tight junction has been discovered as an important structural basis of intercellular connection and may play a key role in intercellular connection injuries or vascular diseases and selenium (Se) deficiency symptoms. Hence, we replicated the Se-deficient broilers model and detected the specific microRNA in response to Se-deficient vein by using quantitative real time-PCR (qRT-PCR) analysis. Also, we selected miR-128-1-5p based on differential expression in vein tissue and confirmed its target gene cell adhesion molecule 1 (CADM1) by the dual luciferase reporter assay and qRT-PCR in VECs. We made the ectopic miR-128-1-5p expression for the purpose of validating its function on tight junction. The result showed that miR-128-1-5p and CADM1 were involved in the ZO-1-mediated tight junction, increased paracellular permeability, and arrested cell cycle. We presumed that miR-128-1-5p and Se deficiency might trigger tight junction. Interestingly, miR-128-1-5p inhibitor and fasudil in part hinder the destruction of the intercellular structure caused by Se deficiency. The miR-128-1-5p/CADM1/tight junction axis provides a new avenue toward understanding the mechanism of Se deficiency, revealing a novel regulation model of tight junction injury in vascular diseases.

The effects of atmospheric hydrogen sulfide on peripheral blood lymphocytes of chickens: Perspectives on inflammation, oxidative stress and energy metabolism.

Excessive hydrogen sulfide (H2S) affects poultry health. Exposure to air pollution induces inflammation, oxidative stress, energy metabolism dysfunction and adverse health effects. However, few detailed studies have been conducted on the molecular mechanisms of H2S-induced injury in poultry. To understand how H2S drives its adverse effects on chickens, twenty-four 14-day-old chickens were randomly divided into two groups. The chickens in the control group were raised in a separate chamber without H2S, and the chickens in the treatment group were exposed to 30 ppm H2S. After 14 days of exposure, peripheral blood samples were taken and the lymphocytes were extracted to detect inflammation, oxidative stress and energy metabolism in broilers. Overall, an increase in the inflammatory response was detected in the peripheral blood lymphocytes following H2S exposure compared to the control group, and the expression levels of the heat shock proteins (HSPs) and the transcription factors nuclear factor κB (NF-κB), cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) were up-regulated in the H2S group, which further suggested that H2S induced an inflammatory response via the NF-κB pathway. Because of the activation of NF-κB, which is a major regulator of oxidative stress, we also observed that reactive oxygen species (ROS) production was elevated under H2S exposure. In addition, we presumed that energy metabolism might be damaged due to the increased ROS production, and we found that H2S down-regulated the expression levels of energy metabolism-related genes, which indicated the occurrence of energy metabolism dysfunction. Altogether, this study suggests that exposure to excessive atmospheric H2S induces an inflammatory response, oxidative stress and energy metabolism dysfunction, providing a reference for comparative medicine.

Hydrogen sulfide inhalation-induced immune damage is involved in oxidative stress, inflammation, apoptosis and the Th1/Th2 imbalance in broiler bursa of Fabricius.

Hydrogen sulfide (H2S) is widely accepted to be a signaling molecule that exhibits some potentially beneficial therapeutic effects at physiological concentrations. At elevated levels, H2S is highly toxic and has a negative effect on human health and animal welfare. Studies have shown that H2S exposure induces an immune function in mice, but there are few studies of the effect of continuous H2S exposure on immune organs in poultry. In this study, one-day-old broilers were selected and exposed to 4 or 20 ppm of H2S gas for 14, 28 and 42 days of age. After exposure, the bursa of Fabricius (BF) was harvested. The results showed that continuous H2S exposure reduced the body weight, abdominal fat percentage, and antibody titer in broilers. H2S exposure also decreased mRNA expression of IgA, IgM and IgG in the broiler BF. A histological study revealed obvious nuclear debris, and a few vacuoles in the BF, and an ultrastructural study revealed mitochondrial and nuclear damage to BF cells after H2S exposure for 42 d. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay suggested H2S exposure remarkably increased the number of TUNEL positive nuclei and significantly increased apoptotic index. The expression of apoptotic genes also confirmed that H2S inhalation damaged the broiler BF. Increased cytokines and reduced antioxidant responses were detected in the BF after exposure to H2S. Cytokines promoted inflammation and caused a Th1/Th2 imbalance. We suggest that continuous H2S intoxication triggers oxidative stress, inflammation, apoptosis and a Th1/Th2 imbalance in the BF, leading to immune injury in broilers.

Resource Destroying Maps.

Resource theory is a widely applicable framework for analyzing the physical resources required for given tasks, such as computation, communication, and energy extraction. In this Letter, we propose a general scheme for analyzing resource theories based on resource destroying maps, which leave resource-free states unchanged but erase the resource stored in all other states. We introduce a group of general conditions that determine whether a quantum operation exhibits typical resource-free properties in relation to a given resource destroying map. Our theory reveals fundamental connections among basic elements of resource theories, in particular, free states, free operations, and resource measures. In particular, we define a class of simple resource measures that can be calculated without optimization, and that are monotone nonincreasing under operations that commute with the resource destroying map. We apply our theory to the resources of coherence and quantum correlations (e.g., discord), two prominent features of nonclassicality.

Hydrogen sulfide attenuates isoflurane-induced neuroapoptosis and cognitive impairment in the developing rat brain.

BACKGROUND: Isoflurane-induced neuroapoptosis and cognitive impairment has been previously reported. Hydrogen sulfide (H2S) has been shown to be a neuromodulator that is thought to have anti-apoptotic, anti-inflammatory, and anti-oxidative benefits. However, it is not known if H2S is protective against anesthesia-induced apoptosis and cognitive defects. METHODS: In this study, postnatal day 7 (P7) Sprague-Dawley rats were randomly divided into four groups: control group (normal saline), H2S group (NaHS 28 µM/kg), isoflurane group (normal saline +0.75% isoflurane) and H2S preconditioning group (NaHS 28 µM/kg + 0.75% isoflurane). After exposure to isoflurane for 6 h, half the numbers of rats in each group were euthanized, and the hippocampus and cerebral cortex were dissected and examined for apoptosis by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) technique and western blot. After 6 weeks, the remaining rats were subjected to a Morris water maze (MWM) test for behavioral assessment. RESULTS: The TUNEL assay and western blot showed that when rats were preconditioned with NaHS, neuroapoptosis decreased significantly both in hippocampus and cerebral cortex compering with the isofulrane group. The MWM showed that P7 rats administration of NaHS improved cognitive impairments induced by isoflurane. CONCLUSIONS: The current study demonstrates that H2S attenuates isoflurane-induced neuroapoptosis and improves cognitive impairments in the developing rat brain.

Behavioral and cardiopulmonary effects of dexmedetomidine-midazolam and dexmedetomidine-midazolam-butorphanol in the silver fox (Vulpes vulpes).

OBJECTIVE: To evaluate the behavior and some cardiopulmonary variables of dexmedetomidine-midazolam or dexmedetomidine-midazolam-butor-phanol in the silver fox (Vulpes vulpes). STUDY DESIGN: Blinded, randomized design. ANIMALS: Sixteen adult silver foxes, aged 7-9 months, weighting 6.0-9.2 kg. METHODS: Animals were randomly assigned to dexmedetomidine (50 µg kg-1) and midazolam (0.45 mg kg-1) (group DM) or to dexmedetomidine (30 µg kg-1), midazolam (0.45 mg kg-1) and butorphanol (0.25 mg kg-1) (group DMB), administered intramuscularly. Pulse rate (PR), respiratory rate (fR), noninvasive arterial pressures, oxygen saturation (SpO2), rectal temperature (T) and behavioral scores (posture, sedation, antinociception, jaw relaxation and auditory response) were measured at 5, 10, 20, 30, 40, 50 and 60 minutes after injection. Time from drug injection to recumbency with no response to stimuli (IT) and time from administration of atipamezole (0.2 mg kg-1) to standing with coordination (RT) were recorded. The occurrences of adverse events were recorded. Data were analyzed by two-tailed unpaired t-tests and Bonferroni post hoc tests. Significant differences were accepted at p<0.05. RESULTS: There were no statistically significant differences between the groups for IT or RT. Arterial pressures were higher in DMB at each time point except at 5 minutes. PR was lower in DM at each time point except at 10 and 60 minutes. No significant difference was found between the groups for fR, SpO2 and T. The behavioral scores were significantly lower (lower quality immobilization) in DMB at 5,10 and 60 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: IT and RT were not different between the groups. Both protocols provided immobilization for 30-40 minutes with excellent muscle relaxation and analgesia adequate for clinical examinations and some simple surgical procedures.

Functional nanoemulsion-hybrid lipid nanocarriers enhance the bioavailability and anti-cancer activity of lipophilic diferuloylmethane.

The purpose of this study was to assess the enhanced physicochemical characteristics, in vitro release behavior, anti-lung cancer activity, gastrointestinal absorption, in vivo bioavailability and bioequivalence of functional nanoemulsion-hybrid lipid nanocarriers containing diferuloylmethane (DNHLNs). The DNHLNs were first fabricated by loading water-in-oil nanoemulsions into hybrid lipid nanosystems using nanoemulsion-thin film-sonication dispersion technologies. The in situ absorption and in vitro and in vivo kinetic features of DNHLNs were measured using an in situ unidirectional perfusion method, a dynamic dialysis method and a plasma concentration-time profile-based method, respectively. The cytotoxic effects of DNHLNs in lung adenocarcinoma A549 cells were examined using MTT colorimetric analysis. The absorptive constants and permeabilities of DNHLNs in four gastrointestinal sections increased by 1.43-3.23 times and by 3.10-7.76 times that of diferuloylmethane (DIF), respectively. The relative bioavailability of DNHLNs to free DIF was 855.02%. DNHLNs inhibited cancer cell growth in a time- and dose-dependent manner. DNHLNs markedly improved the absorption and bioavailability of DIF after oral administration. DNHLNs had stronger inhibitory effects on the viability of A549 cells than that of free DIF. DNHLNs might be potentially promising nanocarriers for DIF delivery via the oral route to address unmet clinical needs.

[Pharmacokinetics and Bioequiavailability of Asparaginase in Asparaginase Nanospheres].

OBJECTIVE: To determine the pharmacokinetics and bioequivalence of self-assembled hyaluronic acid-graft-poly (ethylene glycol)/hydroxypropyl-beta-cyclodextrin hollow nanospheres loaded with asparaginase (AHHPs) in SD rats. METHODS: AHHPs were prepared and observed under transmission electron microscopy. Its size, Zeta potential and entrapment efficiency were detected. Asparaginase (AAS) activities were measured after intravenous injection of AHHPs or free AAS in rats. The pharmacokinetic parameters were calculated using software DAS 2.1.1 for bioequivalence assessment. RESULTS: The self-prepared AHHPs had an average particle size of (367.43 ± 2.72) nm, Zeta potential of (-15. 70 ± 1.25) mV, and average entrapment efficiency of (66.03 ± 3.81)%. The intravenous injection of AHHPs and free AAS produced an area under concentration-time Curve (AUC)(0-48 h) of (162.06 ± 4.01) U/mL · h and (46.38 ± 1.98) U/mL · h, AUC(0-∞) of (203.74 ± 12.91) U/mL · h and (51.44 ± 3.01) U/mL · h, mean residence time (MRT) (0-72h) of (4.35 ± 0.06) h and (1.76 ± 0.06) h, MRT(0-∞) of (7.53 ± 1.05) h and (2.44 ± 0.29) h, peak concentration (Cmax) of (30.37 ± 0.43) U/mL and (26.06 ± 0.88) U/mL, and time to peak concentration (Tmax) of (0.75 ± 0.00) h and (0.08 ± 0.00) h, respectively. Compared with free AAS, the AUC(0-48 h), AUC(0-∞), MRT(0-72 h), MRT(0-∞),Cmax and Tmax of AHHPs increased by 3.5, 4.0, 2.5, 3.1, 1.2 and 9.4 times, respectively. The 90% confidential intervals of AUC(0-48 h), AUC(0.∞) and Cmax of the tested formulation were 72.6%-74.0%, 72.3%-73.7%, 94.7%-96.3%, respectively. CONCLUSION: AHHPs can improve the bioavailability of AAS, extending its biological half-life in rats. AHHPs and free AAS are not bioequivalent.

[Pharmacokinetics and Intestinal Absorption of Curcumin Chitosan Hydrochloride Coated Liposome in Rats].

OBJECTIVE: To investigate the pharmacokinetics and intestinal absorption characteristic of curcumin chitosan hydrochloride coated liposome(CCLP) in SD rats. METHODS: Blood samples were collected after oral administration. Pharmacokinetic parameters were analyzed by DAS program. Rat single pass intestinal perfusion method was employed to investigate the absorption mechanism. RESULTS: The AUC0-t, AUC0-∞, t1/2, and Cmax of CCLP were 1. 73-fold, 1. 95-fold, 1. 56-fold and 1. 91-fold of the free drug. The intestinal absorption rate constant (Ka) of CCLP in duodenum, jejunum, ileum and colon were 1. 48, 1. 28, 1. 17 , and 4. 01 times as much as the free drug and the effective permeability(Peff) of CCLP were 1. 58, 1.-33, 1. 30 and 4. 55 times of the free drug, respectively. CONCLUSION: The bioavailability of CCLP in rats is increased remarkably and Ka is increased in various intestinal segments by CCLP, especially in colon, as well as Peff.

[Pharmacokinetics Study on Curcumin Hydroxypropyl-ß-Cyclodextrin Phospholipid Complex in Rats].

OBJECTIVE: To compare the in vivo pharmacokinetics of curcumin hydroxypropyl-ß-cyclodextrin phospholipid complex, curcumin hydroxypropyl-ß-cyclodextrin and curcumin phospholipid complex, and to discuss the advantage of hydroxypropyl-ß-cyclodextrin phospholipid complex as carrier. METHODS: Drawing blood after SD rats were oral administered with the above preparations and free drug at 50 mg/kg( corresponding to curcumin) , and the blood concentration were determined by HPLC. RESULTS: The AUC0-∞ of curcumin hydroxypropyl-ß-cyclodextrin phospholipid complex was(1 126. 20 ± 323. 24) g/(L . h), which was 5. 89, 1. 49 and 1. 17 times as curcumin (191. 08 ± 43. 27) µg/( L . h), curcumin phospholipid complex(754. 93 ± 55. 33) µg/(L . h), curcumin hydroxypropyl-ß- cyclodextrin(961. 21 ± 253. 65) µg/(L . h). CONCLUSION: The curcumin hydroxypropyl-ß-cyclodextrin phospholipid complex has a better absorption property than curcumin phospholipid complex and curcumin hydroxypropyl-ß-cyclodextrin, which is more beneficial to improve the bioavailability.

Azithromycin cationic non-lecithoid nano/microparticles improve bioavailability and targeting efficiency.

PURPOSE: The purpose of this study was to develop and evaluate the azithromycin cationic non-lecithoid nano/microparticles with high bioavailability and lung targeting efficiency. METHODS: The cationic niosomes with different sizes (AMCNS-S and AMCNS-L) along with varied built-in characteristics were produced to achieve high bioavailability and lung targeting efficiency of azithromycin (AM) via two administration routes widely used in clinical practice, i.e., oral and intravenous routes, instead of transdermal route (by which the only marketed niosome-based drug delivery dermatologic products were given). The possible explanations for improved bioavailability and lung targeting efficacy were put forward here. RESULTS: AMCNS-S (or AMCNS-L) had high bioavailability, for example, the oral (or intravenous) relative bioavailability of AMCNS-S (or AMCNS-L) to free AM increased to 273.19% (or 163.50%). After intravenous administration, AMCNS-S (or AMCNS-L) had obvious lung targeting efficiency, for example, the lung AM concentration of AMCNS-S (or AMCNS-L) increased 16 (or 28) times that of free AM at 12 h; the AM concentration of AMCNS-S (or AMCNS-L) in lung was higher than that in heart and kidney all the time. CONCLUSIONS: The development of niosome-based AM nanocarriers provides valuable tactics in antibacterial therapy and in non-lecithoid niosomal application.