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1.
World J Gastrointest Surg ; 16(5): 1311-1319, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38817296

ABSTRACT

BACKGROUND: Laparoscopic gastrectomy for esophagogastric junction (EGJ) carcinoma enables the removal of the carcinoma at the junction between the stomach and esophagus while preserving the gastric function, thereby providing patients with better treatment outcomes and quality of life. Nonetheless, this surgical technique also presents some challenges and limitations. Therefore, three-dimensional reconstruction visualization technology (3D RVT) has been introduced into the procedure, providing doctors with more comprehensive and intuitive anatomical information that helps with surgical planning, navigation, and outcome evaluation. AIM: To discuss the application and advantages of 3D RVT in precise laparoscopic resection of EGJ carcinomas. METHODS: Data were obtained from the electronic or paper-based medical records at The First Affiliated Hospital of Hebei North University from January 2020 to June 2022. A total of 120 patients diagnosed with EGJ carcinoma were included in the study. Of these, 68 underwent laparoscopic resection after computed tomography (CT)-enhanced scanning and were categorized into the 2D group, whereas 52 underwent laparoscopic resection after CT-enhanced scanning and 3D RVT and were categorized into the 3D group. This study had two outcome measures: the deviation between tumor-related factors (such as maximum tumor diameter and infiltration length) in 3D RVT and clinical reality, and surgical outcome indicators (such as operative time, intraoperative blood loss, number of lymph node dissections, R0 resection rate, postoperative hospital stay, postoperative gas discharge time, drainage tube removal time, and related complications) between the 2D and 3D groups. RESULTS: Among patients included in the 3D group, 27 had a maximum tumor diameter of less than 3 cm, whereas 25 had a diameter of 3 cm or more. In actual surgical observations, 24 had a diameter of less than 3 cm, whereas 28 had a diameter of 3 cm or more. The findings were consistent between the two methods (χ2 = 0.346, P = 0.556), with a kappa consistency coefficient of 0.808. With respect to infiltration length, in the 3D group, 23 patients had a length of less than 5 cm, whereas 29 had a length of 5 cm or more. In actual surgical observations, 20 cases had a length of less than 5 cm, whereas 32 had a length of 5 cm or more. The findings were consistent between the two methods (χ2 = 0.357, P = 0.550), with a kappa consistency coefficient of 0.486. Pearson correlation analysis showed that the maximum tumor diameter and infiltration length measured using 3D RVT were positively correlated with clinical observations during surgery (r = 0.814 and 0.490, both P < 0.05). The 3D group had a shorter operative time (157.02 ± 8.38 vs 183.16 ± 23.87), less intraoperative blood loss (83.65 ± 14.22 vs 110.94 ± 22.05), and higher number of lymph node dissections (28.98 ± 2.82 vs 23.56 ± 2.77) and R0 resection rate (80.77% vs 61.64%) than the 2D group. Furthermore, the 3D group had shorter hospital stay [8 (8, 9) vs 13 (14, 16)], time to gas passage [3 (3, 4) vs 4 (5, 5)], and drainage tube removal time [4 (4, 5) vs 6 (6, 7)] than the 2D group. The complication rate was lower in the 3D group (11.54%) than in the 2D group (26.47%) (χ2 = 4.106, P < 0.05). CONCLUSION: Using 3D RVT, doctors can gain a more comprehensive and intuitive understanding of the anatomy and related lesions of EGJ carcinomas, thus enabling more accurate surgical planning.

2.
World J Gastrointest Surg ; 15(8): 1693-1702, 2023 Aug 27.
Article in English | MEDLINE | ID: mdl-37701684

ABSTRACT

BACKGROUND: For treatment of hilar cholangiocarcinoma (HCCA), the rate of radical resection is low and prognosis is poor, and preoperative evaluation is not sufficiently accurate. 3D visualization has the advantage of giving a stereoscopic view, which makes accurate resection of HCCA possible. AIM: To establish precise resection of HCCA based on eOrganmap 3D reconstruction and full quantification technology. METHODS: We retrospectively analyzed the clinical data of 73 patients who underwent HCCA surgery. All patients were assigned to two groups. The traditional group received traditional 2D imaging planning before surgery (n = 35). The eOrganmap group underwent 3D reconstruction and full quantitative technical planning before surgery (n = 38). The preoperative evaluation, anatomical classification of hilar hepatic vessels, indicators associated with surgery, postoperative complications, liver function, and stress response indexes were compared between the groups. RESULTS: Compared with the traditional group, the amount of intraoperative blood loss in the eOrganmap group was lower, the operating time and postoperative intestinal ventilation time were shorter, and R0 resection rate and lymph node dissection number were higher (P < 0.05). The total complication rate in the eOrganmap group was 21.05% compared with 25.71% in the traditional group (P > 0.05). The levels of total bilirubin, Albumin (ALB) , aspartate transaminase, and alanine transaminase in the eOrganmap group were significantly different from those in the traditional group (intergroup effect: F = 450.400, 79.120, 95.730, and 13.240, respectively; all P < 0.001). Total bilirubin, aspartate transaminase, and alanine transaminase in both groups showed a decreasing trend with time (time effect: F = 30.270, 17.340, and 13.380, respectively; all P < 0.001). There was an interaction between patient group and time (interaction effect: F = 3.072, 2.965, and 2.703, respectively; P = 0.0282, 0.032, and 0.046, respectively); ALB levels in both groups tended to increase with time (time effect: F = 22.490, P < 0.001), and there was an interaction effect between groups and time (interaction effect: F = 4.607, P = 0.004). In the eOrganmap group, there was a high correlation between the actual volume of intraoperative liver specimen resection and the volume of preoperative virtual liver resection (t = 0.916, P < 0.001). CONCLUSION: The establishment of accurate laparoscopic resection of hilar cholangiocarcinoma based on preoperative eOrganmap 3D reconstruction and full quantization technology can make laparoscopic resection of hilar cholangiocarcinoma more accurate and safe.

3.
Polymers (Basel) ; 15(14)2023 Jul 22.
Article in English | MEDLINE | ID: mdl-37514511

ABSTRACT

Hemorrhagic shock is the primary cause of death in patients with severe trauma, and the development of rapid and efficient hemostatic methods is of great significance in saving the lives of trauma patients. In this study, a polycaprolactone (PCL) nanofiber membrane was prepared by electrospinning. A PCL-PDA loading system was developed by modifying the surface of polydopamine (PDA), using inspiration from mussel adhesion protein, and the efficient and stable loading of thrombin (TB) was realized to ensure the bioactivity of TB. The new thrombin loading system overcomes the disadvantages of harsh storage conditions, poor strength, and ease of falling off, and it can use thrombin to start a rapid coagulation cascade reaction, which has the characteristics of fast hemostasis, good biocompatibility, high safety, and a wide range of hemostasis. The physicochemical properties and biocompatibility of the PCL-PDA-TB membrane were verified by scanning electron microscopy, the cell proliferation test, the cell adhesion test, and the extract cytotoxicity test. Red blood cell adhesion, platelet adhesion, dynamic coagulation time, and animal models all verified the coagulation effect of the PCL-PDA-TB membrane. Therefore, the PCL-PDA-TB membrane has great potential in wound hemostasis applications, and should be widely used in various traumatic hemostatic scenarios.

4.
Carbohydr Polym ; 309: 120678, 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-36906361

ABSTRACT

Strong and ductile sodium alginate (SA) reinforced polyacrylamide (PAM)/xanthan gum (XG) double network ionic hydrogels were constructed for stress sensing and self-powered wearable device applications. In the designed network of PXS-Mn+/LiCl (short for PAM/XG/SA-Mn+/LiCl, where Mn+ stands for Fe3+, Cu2+ or Zn2+), PAM acts as a flexible hydrophilic skeleton, and XG functions as a ductile second network. The macromolecule SA interacts with metal ion Mn+ to form a unique complex structure, significantly improving the mechanical strength of the hydrogel. The addition of inorganic salt LiCl endows the hydrogel with high electrical conductivity, and meanwhile reduces the freezing point and prevents water loss of the hydrogel. PXS-Mn+/LiCl exhibits excellent mechanical properties and ultra-high ductility (a fracture tensile strength up to 0.65 MPa and a fracture strain up to 1800%), and high stress-sensing performance (a high GF up to 4.56 and pressure sensitivity of 0.122). Moreover, a self-powered device with a dual-power-supply mode, i.e., PXS-Mn+/LiCl-based primary battery and TENG, and a capacitor as the energy storage component was constructed, which shows promising prospects for self-powered wearable electronics.

5.
ACS Sens ; 6(8): 2938-2951, 2021 08 27.
Article in English | MEDLINE | ID: mdl-34328311

ABSTRACT

A biocompatible, flexible, yet robust conductive composite hydrogel (CCH) for wearable pressure/strain sensors has been achieved by an all-solution-based approach. The CCH is rationally constructed by in situ polymerization of aniline (An) monomers in the polyvinyl alcohol (PVA) matrix, followed by the cross-linking of PVA with glutaraldehyde (GA) as the cross-linker. The unique multiple synergetic networks in the CCH including strong chemical covalent bonds and abundance of weak physical cross-links, i.e., hydrogen bondings and electrostatic interactions, impart excellent mechanical strength (a fracture tensile strength of 1200 kPa), superior compressibility (ε = 80%@400 kPa), outstanding stretchability (a fracture strain of 670%), high sensitivity (0.62 kPa-1 at a pressure range of 0-1.0 kPa for pressure sensing and a gauge factor of 3.4 at a strain range of 0-300% for strain sensing, respectively), and prominent fatigue resistance (1500 cycling). As the flexible wearable sensor, the CCH is able to monitor different types of human motion and diagnostically distinguish speaking. As a proof of concept, a sensing device has been designed for the real-time detection of 2D distribution of weight or pressure, suggesting its promising potentials for electronic skin, human-machine interaction, and soft robot applications.


Subject(s)
Hydrogels , Wearable Electronic Devices , Electric Conductivity , Humans , Monitoring, Physiologic , Polyvinyl Alcohol
6.
Chem Commun (Camb) ; 56(61): 8675-8678, 2020 Aug 07.
Article in English | MEDLINE | ID: mdl-32613966

ABSTRACT

Co-Pt bimetallic nanoparticles with adjustable composition and particle size were prepared by the combination of atomic layer deposition and H2 post-deposition annealing. The structure, magnetic and electrocatalytic properties of Co-Pt bimetallic nanoparticles can be facilely tuned by controlling the composition.

7.
J Phys Condens Matter ; 31(24): 245002, 2019 Jun 19.
Article in English | MEDLINE | ID: mdl-30865938

ABSTRACT

La0.7Sr0.3VO3 (LSVO) thin films, 5-30 unit cells (u.c.) in thickness, have been epitaxially deposited on (0 0 1) SrTiO3 (STO) single crystal substrates. Although LSVO is metallic in bulk, insulating behavior is observed, from 2 to 390 K, in LSVO films less than 9 u.c. in thickness, while thicker films show a metal-insulator transition with the critical temperature increasing with the decrease of film thickness. X-ray absorption spectra reveal a charge transfer across the LSVO/STO interface for a continuous increase of V valence in LSVO, as well as a decrease of Ti valence in interfacial STO, with the LSVO film thickness increases. The transport characteristics are discussed in terms of enhanced electron localization due to the reduction of film thickness and V 3d band filling induced by the charge transfer.

8.
ACS Appl Mater Interfaces ; 9(7): 6634-6643, 2017 Feb 22.
Article in English | MEDLINE | ID: mdl-28139921

ABSTRACT

Al2O3- or HfO2-based nanocomposite structures with embedded CoPtx nanocrystals (NCs) on TiN-coated Si substrates have been prepared by combination of thermal atomic layer deposition (ALD) and plasma-enhanced ALD for resistive random access memory (RRAM) applications. The impact of CoPtx NCs and their average size/density on the resistive switching properties has been explored. Compared to the control sample without CoPtx NCs, ALD-derived Pt/oxide/100 cycle-CoPtx NCs/TiN/SiO2/Si exhibits a typical bipolar, reliable, and reproducible resistive switching behavior, such as sharp distribution of RRAM parameters, smaller set/reset voltages, stable resistance ratio (≥102) of OFF/ON states, better switching endurance up to 104 cycles, and longer data retention over 105 s. The possible resistive switching mechanism based on nanocomposite structures of oxide/CoPtx NCs has been proposed. The dominant conduction mechanisms in low- and high-resistance states of oxide-based device units with embedded CoPtx NCs are Ohmic behavior and space-charge-limited current, respectively. The insertion of CoPtx NCs can effectively improve the formation of conducting filaments due to the CoPtx NC-enhanced electric field intensity. Besides excellent resistive switching performances, the nanocomposite structures also simultaneously present ferromagnetic property. This work provides a flexible pathway by combining PEALD and TALD compatible with state-of-the-art Si-based technology for multifunctional electronic devices applications containing RRAM.

9.
Clin Ther ; 37(7): 1517-28, 2015 Jul 01.
Article in English | MEDLINE | ID: mdl-26048185

ABSTRACT

PURPOSE: Simplification of therapeutic regimens for patients with type 2 diabetes mellitus can provide convenience that leads to improved compliance. Dapagliflozin/metformin extended-release (XR) fixed-dose combination (FDC) tablets offer the convenience of once-daily dosing. Two pharmacokinetic (PK) studies were conducted to establish bioequivalence for 2 doses of dapagliflozin/metformin XR FDC versus the same dosage of the individual component (IC) tablets in healthy adults. METHODS: Two open-label, randomized, 4-period, 4-arm crossover studies were conducted to assess the bioequivalence and PK properties of dapagliflozin and metformin FDCs in healthy subjects under fed and fasting conditions. Participants received single oral doses or once-daily dosing of dapagliflozin/metformin XR (5 mg/500 mg [study 1] or 10 mg/1000 mg [study 2]) for 4 days in an FDC formulation or corresponding strengths of IC tablets. FINDINGS: For both of the studies, dapagliflozin and metformin 5 mg/500 mg or 10 mg/1000 mg FDC tablets were bioequivalent to the respective IC tablets. The 90% CIs of the ratio of the adjusted geometric means for all key PK parameters (Cmax, AUC0-T, and AUC0-∞) were contained within the predefined 0.80 to 1.25 range to conclude bioequivalence for both dapagliflozin and metformin. Once-daily dosing to steady state of each FDC tablet had no effect on the PK properties of dapagliflozin or metformin. When the FDCs were administered with a light-fat meal, there was no effect on metformin PK values and only a modest, nonclinically meaningful effect on dapagliflozin PK values. There were no safety or tolerability concerns. IMPLICATIONS: Bioequivalence of the FDCs of dapagliflozin/metformin XR and the ICs was established, and no safety issues of clinical concern were raised.


Subject(s)
Benzhydryl Compounds/blood , Food-Drug Interactions/physiology , Glucosides/blood , Hypoglycemic Agents/blood , Metformin/blood , Adult , Benzhydryl Compounds/administration & dosage , Benzhydryl Compounds/adverse effects , Benzhydryl Compounds/therapeutic use , Chemistry, Pharmaceutical , Cross-Over Studies , Delayed-Action Preparations , Drug Administration Schedule , Drug Combinations , Fasting , Female , Glucosides/administration & dosage , Glucosides/adverse effects , Glucosides/therapeutic use , Healthy Volunteers , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Male , Metformin/administration & dosage , Metformin/adverse effects , Metformin/therapeutic use , Middle Aged , Tablets , Therapeutic Equivalency , Young Adult
10.
Sci Rep ; 5: 7933, 2015 Jan 21.
Article in English | MEDLINE | ID: mdl-25604754

ABSTRACT

For ferromagnets, varying from simple metals to strongly correlated oxides,the critical behaviors near the Curie temperature (T(C)) can be grouped into several universal classes. In this paper, we report an unusual critical behavior in manganese nitrides Cu(1-x)NMn(3+x) (0.1 ≤ x ≤ 0.4). Although the critical behavior below T(C) can be well described by mean field (MF) theory, robust critical fluctuations beyond the expectations of any universal classes are observed above T(C) in x = 0.1. The critical fluctuations become weaker when x increases, and the MF-like critical behavior is finally restored at x = 0.4. In addition, the paramagnetic susceptibility of all the samples deviates from the Curie-Weiss (CW) law just above T(C). This deviation is gradually smeared as x increases. The short-range antiferromagnetic ordering above T(C) revealed by our electron spin resonance measurement explains both the unusual critical behavior and the breakdown of the CW law.

11.
ACS Appl Mater Interfaces ; 6(10): 6998-7003, 2014 May 28.
Article in English | MEDLINE | ID: mdl-24828839

ABSTRACT

In this paper, an anti-icing coating with an aqueous lubricating layer is reported. This anti-icing coating can be directly applied to various substrates, and the ice adhesion strength on the coated surfaces can be lowered greatly as compared to uncoated substrates. We demonstrate for the first time that the formed ice on this anti-icing coating can be blown off by a wind action in the wind tunnel with a controlled temperature and wind velocity. Moreover, the low ice adhesion of the anti-icing coating can be maintained even when the temperature is lowered to -53 °C. The robustness and durability of the anti-icing coating are proved by the icing/de-icing experiments. The results show that the anti-icing coating with an aqueous lubricating layer is of great promise for practical applications.

12.
ACS Appl Mater Interfaces ; 5(10): 4026-30, 2013 May 22.
Article in English | MEDLINE | ID: mdl-23642212

ABSTRACT

A robust prototypical anti-icing coating with a self-lubricating liquid water layer (SLWL) is fabricated via grafting cross-linked hygroscopic polymers inside the micropores of silicon wafer surfaces. The ice adhesion on the surface with SLWL is 1 order of magnitude lower than that on the superhydrophobic surfaces and the ice formed atop of it can be blown off by an action of strong breeze. The surface with self-lubricating liquid water layer exhibits excellent capability of self-healing and abrasion resistance. The SLWL surface should also find applications in antifogging and self-cleaning by rainfall, in addition to anti-icing and antifrosting.

14.
Proc Natl Acad Sci U S A ; 109(15): E879-88, 2012 Apr 10.
Article in English | MEDLINE | ID: mdl-22434910

ABSTRACT

T cell-dependent B-cell responses decline with age, suggesting defective CD4 T-cell function. CD4 memory T cells from individuals older than 65 y displayed increased and sustained transcription of the dual-specific phosphatase 4 (DUSP4) that shortened expression of CD40-ligand (CD40L) and inducible T-cell costimulator (ICOS) (both P < 0.001) and decreased production of IL-4, IL-17A, and IL-21 (all P < 0.001) after in vitro activation. In vivo after influenza vaccination, activated CD4 T cells from elderly individuals had increased DUSP4 transcription (P = 0.002), which inversely correlated with the expression of CD40L (r = 0.65, P = 0.002), ICOS (r = 0.57, P = 0.008), and IL-4 (r = 0.66, P = 0.001). In CD4 KO mice reconstituted with DUSP4 OT-II T cells, DUSP4 had a negative effect on the expansion of antigen-specific B cells (P = 0.003) and the production of ova-specific antibodies (P = 0.03) after immunization. Silencing of DUSP4 in memory CD4 T cells improved CD40L (P < 0.001), IL-4 (P = 0.007), and IL-21 (P = 0.04) expression significantly more in the elderly than young adults. Consequently, the ability of CD4 memory T cells to support B-cell differentiation that was impaired in the elderly (P = 0.004) was restored. Our data suggest that increased DUSP4 expression in activated T cells in the elderly in part accounts for defective adaptive immune responses.


Subject(s)
Aging/immunology , B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/enzymology , Dual-Specificity Phosphatases/metabolism , Mitogen-Activated Protein Kinase Phosphatases/metabolism , Protein Tyrosine Phosphatases/metabolism , Signal Transduction/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Aging/genetics , Animals , Biomarkers , CD4-Positive T-Lymphocytes/immunology , Gene Silencing , Humans , Immunity, Humoral/immunology , Immunologic Memory/genetics , Influenza, Human/immunology , Lymphocyte Activation/immunology , Mice , T-Lymphocytes, Helper-Inducer/immunology , Vaccination , Young Adult
15.
Int J Biol Macromol ; 50(3): 701-6, 2012 Apr 01.
Article in English | MEDLINE | ID: mdl-22266328

ABSTRACT

A novel substance, cationic acetylcholine potato starch (CAPS), was developed for the first time. The synthesis process had three steps: first, carboxymethyl potato starch (CMPS) was synthesized under sodium hydroxide alkaline condition and in isopropyl alcohol organic media; second, bromocholine chloride (BCC) was synthesized with sulphuric acid as a catalytic agent; finally, CAPS was synthesized by the reaction of CMPS with BCC in N,N'-dimethylformamide (DMF). The degree of substitution (DS) of CAPS was determined by ammonia gas-sensing electrode and elemental analysis. CAPS was characterized by Fourier transformed infrared (FTIR) and near infrared (FTNIR) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD) and differential scanning calorimetry (DSC).


Subject(s)
Acetylcholine/chemistry , Chemistry Techniques, Synthetic/methods , Solanum tuberosum/chemistry , Starch/analogs & derivatives , Starch/chemical synthesis , Calorimetry, Differential Scanning , Microscopy, Electron, Scanning , Spectroscopy, Fourier Transform Infrared , Starch/chemistry , X-Ray Diffraction
16.
Int J Biol Macromol ; 50(1): 250-6, 2012 Jan 01.
Article in English | MEDLINE | ID: mdl-22100869

ABSTRACT

This study was carried out to develop a new type of modified starch based on α-amylase and glucoamylase. The structural and chemical characteristics of the porous starch were determined by Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The potential application of the porous starch as an adsorbent was evaluated using methyl violet as an adsorbed model. The adsorption capacity was optimized by investigating the reaction factors, including the mass ratio of α-amylase to glucoamylase (m(α-amylase)/m(glucoamylase)), the mass ratio of total amount of enzymes to starch (m(enzyme)/m(St)), the ratio of liquid volume to starch mass (V(H2O)/M(St)), pH value of the reaction solution, enzymatic reaction temperature, and enzymatic reaction time. The hydrolysis ratio of each sample was also determined to investigate the effect of different reaction conditions on the hydrolysis degree. The results suggest that the porous starch has a more excellent adsorption capacity than the native starch, and may be expected to have wide potential applications in many fields.


Subject(s)
Starch/chemistry , Zea mays/chemistry , Adsorption , Calorimetry, Differential Scanning/methods , Glucan 1,4-alpha-Glucosidase/chemistry , Hydrogen-Ion Concentration , Hydrolysis , Microscopy, Electron, Scanning/methods , Porosity , Spectroscopy, Fourier Transform Infrared/methods , Temperature , Time Factors , X-Ray Diffraction , alpha-Amylases/chemistry
18.
Int J Biol Macromol ; 49(5): 1083-91, 2011 Dec 01.
Article in English | MEDLINE | ID: mdl-21925204

ABSTRACT

The aim of this study was to prepare oxidized guar gum with a simple dry method, basing on guar gum, hydrogen peroxide and a small amount of solvent. To obtain a product with suitable viscosity for reactive dye printing, the effects of various factors such as the amount of oxidant and solvent, reaction temperature and time were studied with respect to the viscosity of reaction products. The product was characterized by Fourier transform infrared spectroscopy, size exclusion chromatography, scanning electron microscopy and differential scanning calorimetry. The hydrated rate of guar gum and oxidized guar gum was estimated through measuring the required time when their solutions (1%, w/v) reached the maximum viscosity. The effects of the salt concentration and pH on viscosity of the resultant product were studied. The mixed paste containing oxidized guar gum and carboxymethyl starch was prepared and its viscosity was determined by the viscometer. The rheological property of the mixed paste was appraised by the printing viscosity index. In addition, the applied effect of mixed paste in reactive dye printing was examined by assessing the fabric stiffness, color yield and sharp edge to the printed image in comparison with sodium alginate. And the results indicated that the mixed paste could partially replace sodium alginate as thickener in reactive dye printing. The study also showed that the method was low cost and eco-friendly and the product would have an extensive application in reactive dye printing.


Subject(s)
Coloring Agents/chemistry , Galactans/chemistry , Green Chemistry Technology , Hydrogen Peroxide/chemistry , Mannans/chemistry , Plant Gums/chemistry , Printing/methods , Alginates/chemistry , Calorimetry, Differential Scanning , Chromatography, Gel , Glucuronic Acid/chemistry , Hexuronic Acids/chemistry , Hydrogen-Ion Concentration , Microscopy, Electron, Scanning , Oxidation-Reduction , Rheology , Salts/chemistry , Solubility , Spectroscopy, Fourier Transform Infrared , Starch/analogs & derivatives , Starch/chemistry , Viscosity
19.
AAPS J ; 12(3): 407-16, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20461486

ABSTRACT

gamma-Hydroxybutyric acid (GHB), a drug of abuse, exhibits saturable renal clearance and capacity-limited metabolism. The objectives of this study were to construct a mechanistic toxicokinetic (TK) model describing saturable renal reabsorption and capacity-limited metabolism of GHB and to predict the effects of inhibition of renal reabsorption on GHB TK in the plasma and urine. GHB was administered by iv bolus (200-1,000 mg/kg) to male Sprague-Dawley rats and plasma and urine samples were collected for up to 6 h post-dose. GHB concentrations were determined by LC/MS/MS. GHB plasma concentration and urinary excretion were well-described by a TK model incorporating plasma and kidney compartments, along with two tissue and two ultrafiltrate compartments. The estimate of the Michaelis-Menten constant for renal reabsorption (K (m,R)) was 0.46 mg/ml which is consistent with in vitro estimates of monocarboxylate transporter (MCT)-mediated uptake of GHB (0.48 mg/ml). Simulation studies assessing inhibition of renal reabsorption of GHB demonstrated increased time-averaged renal clearance and GHB plasma AUC, independent of the inhibition mechanism assessed. Co-administration of GHB (600 mg/kg iv) and L: -lactate (330 mg/kg iv bolus plus 121 mg/kg/h iv infusion), a known inhibitor of MCTs, resulted in a significant decrease in GHB plasma AUC and an increase in time-averaged renal clearance, consistent with the model simulations. These results suggest that inhibition of renal reabsorption of GHB is a viable therapeutic strategy for the treatment of GHB overdoses. Furthermore, the mechanistic TK model provides a useful in silico tool for the evaluation of potential therapeutic strategies.


Subject(s)
Hydroxybutyrates/pharmacokinetics , Hydroxybutyrates/toxicity , Kidney/drug effects , Animals , Area Under Curve , Hydroxybutyrates/blood , Hydroxybutyrates/urine , Kidney/metabolism , Male , Rats , Rats, Sprague-Dawley
20.
Int J Pharm ; 385(1-2): 86-91, 2010 Jan 29.
Article in English | MEDLINE | ID: mdl-19879345

ABSTRACT

A simple method has been developed to prepare smart P(N,N-diethylacrylamide-co-methacrylic acid) (P(DEA-co-MAA)) microspheres that consist of well-defined temperature-sensitive cores and pH sensitive shells. The microgels have been prepared by surfactant-free emulsion polymerization using water as the solvent. The core-shell hydrogel microspheres have been characterized by Fourier transform infrared (FTIR) spectroscopy, UV spectrometry, dynamic light scattering (DLS) and transmission electron micrograph (TEM). Preliminary characterization of the biocompatibility of hydrogel microspheres has been done by the cytotoxicity assays using the HeLa human breast cancer cell line as probes. The in vitro drug release indicates that drug release rate, encapsulation efficiency (EE) and release kinetics depend upon the pH value and copolymer composition. According to this study, the hydrogel microspheres based on P(DEA-co-MAA) could serve as suitable candidate for drug site-specific carrier in intestine.


Subject(s)
Acrylamides/chemistry , Drug Carriers , Hydrogels , Microspheres , Polymers/chemistry , Polymethacrylic Acids/chemistry , Serum Albumin, Bovine/chemistry , Acrylamides/toxicity , Cell Survival/drug effects , Chemistry, Pharmaceutical , Delayed-Action Preparations , Diffusion , Dose-Response Relationship, Drug , HeLa Cells , Humans , Hydrogen-Ion Concentration , Hydrophobic and Hydrophilic Interactions , Kinetics , Light , Microscopy, Electron, Transmission , Models, Chemical , Polymers/toxicity , Polymethacrylic Acids/toxicity , Scattering, Radiation , Solubility , Solvents/chemistry , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared , Surface Properties , Technology, Pharmaceutical/methods , Temperature , Water/chemistry
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