Enhanced Tumor Accumulation of Low-Molecular-Weight Hyaluronic Acid/Chitosan Nanocomplexes for Photothermal Therapy.

Targeted phototheranostic nanosystems involving both cancer-specific near-infrared (NIR) fluorescence imaging and NIR light-induced phototherapy have shown great potential to improve cancer detection and treatment. In this study, a bifunctional nanocomplex based on low-molecular-weight hyaluronic acid (LMW-HA) and chitosan oligosaccharide lactate (COL) conjugating a zwitterionic NIR dye (ZW800-1) was rationally designed and prepared, and it was simultaneously used to enhance tumor accumulation and photothermal therapy (PTT). When HA-COL-ZW nanocomplexes were intravenously injected into mice bearing NCI-H460 tumors, HA-COL-ZW revealed increased tumor accumulation with prolonged tumor retention. Moreover, the ZW800-1 incorporated in HA-COL-ZW nanocomplexes showed excellent capability to convert NIR light into heat energy at the tumor site, acting as a PTT agent. Therefore, the targeted phototherapeutic HA-COL-ZW nanocomplex is a biocompatible and effective photothermal nanoagent, which could be a good candidate for future clinical use.

Enhanced Tumor Uptake and Retention of Cyanine Dye-Albumin Complex for Tumor-Targeted Imaging and Phototherapy.

Heptamethine cyanine dyes are widely used for in vivo near-infrared (NIR) fluorescence imaging and NIR laser-induced cancer phototherapy due to their good optical properties. Since most of heptamethine cyanine dyes available commercially are highly hydrophobic, they can usually be used for in vivo applications after formation of complexes with blood plasma proteins, especially serum albumin, to increase aqueous solubility. The complex formation between cyanine dyes and albumin improves the chemical stability and optical property of the hydrophobic cyanine dyes, which is the bottom of their practical use. In this study, the complexes between three different heptamethine cyanine dyes, namely clinically available indocyanine green (ICG), commercially available IR-786 and zwitterionic ZW800-Cl, and bovine serum albumin (BSA), were prepared to explore the effect of cyanine dyes on their tumor uptake and retention. Among the three complexes, IR-786©BSA exhibited increased tumor accumulation with prolonged tumor retention, compared to other complexes. Moreover, IR-786 bound to BSA played an important role in tumor growth suppression due to its cytotoxicity. To achieve complete tumor ablation, the tumor targeted by IR-786©BSA was further exposed to 808 nm laser irradiation for effective photothermal cancer treatment.

Tumor Targeting by Conjugation of Chlorambucil with Zwitterionic Near-Infrared Fluorophore for Cancer Phototherapy.

Improving the tumor targeting of anticancer drugs to minimize systemic exposure remains challenging. The chemical conjugation of anticancer drugs with various near-infrared (NIR) fluorophores may provide an effective approach to improve NIR laser-induced cancer phototherapy. Towards this end, the selection of NIR fluorophores conjugated with hydrophobic anticancer drugs is an important consideration for targeted cancer photothermal therapy (PTT). In this study, a highly water-soluble zwitterionic NIR fluorophore (ZW800) was prepared to conjugate with a water-insoluble anticancer drug, chlorambucil (CLB), to improve tumor targeting, in vivo biodistribution, and PTT performance. The in vivo results using an HT-29 xenograft mouse model demonstrated that the CLB-ZW800 conjugate not only exhibited high tumor accumulation within 4 h after injection, but also showed rapid body clearance behavior for less systemic toxicity. Furthermore, the tumor tissue targeted by the CLB-ZW800 conjugate was exposed to 808 nm NIR laser irradiation to generate photothermal energy and promote apoptotic cell death for the effective PTT of cancer. Therefore, this study provides a feasible strategy for developing bifunctional PTT agents capable of tumor-targeted imaging and phototherapy by the conjugation of small molecule drugs with the versatile zwitterionic NIR fluorophore.

Tumor Targeting with Methotrexate-Conjugated Zwitterionic Near-Infrared Fluorophore for Precise Photothermal Therapy.

Targeted tumor imaging can effectively enable image-guided surgery and precise cancer therapy. Finding the right combination of anticancer drugs and near-infrared (NIR) fluorophores is the key to targeted photothermal cancer treatment. In this study, a tumor-targetable NIR fluorophore conjugate with rapid body clearance was developed for accurate tumor imaging and effective photothermal therapy (PTT). The methotrexate (MTX) and zwitterionic NIR fluorophore conjugate (MTX-ZW) were prepared by conjugating a folate antagonist MTX with an aminated ZW800-1 analog to increase the tumor targetability for NIR laser-based PTT of cancer. The MTX, known as a poor tumor-selective drug, showed high tumor accumulation and rapid background clearance after conjugation with the highly water-soluble zwitterionic NIR fluorophore up to 4 h post-injection. The photothermal energy was generated from the MTX-ZW conjugate to induce necrotic cell death in the targeted tumor site under 808 nm laser irradiation. Compared with the previously reported MTX conjugates, the MTX-ZW conjugate can be a great candidate for targeted tumor imaging and fluorescence-guided photothermal cancer therapy. Therefore, these results provide a strategy for the design of drug-fluorophore conjugates and elaborate therapeutic platforms for cancer phototherapy.

Reframing Patient Experience Approaches and Methods to Achieve Patient-Centeredness in Healthcare: Scoping Review.

(1) There has been growing attention among healthcare researchers on new and innovative methodologies for improving patient experience. This study reviewed the approaches and methods used in current patient experience research by applying the perspective of design thinking to discuss practical methodologies for a patient-centered approach and creative problem-solving. (2) A scoping review was performed to identify research trends in healthcare. A four-stage design thinking process ("Discover", "Define", "Develop", and "Deliver") and five themes ("User focus", "Problem-framing", "Visualization", "Experimentation", and "Diversity"), characterizing the concept, were used for the analysis framework. (3) After reviewing 67 studies, the current studies show that the iterative process of divergent and convergent thinking is lacking, which is a core concept of design thinking, and it is necessary to employ an integrative methodology to actively apply collaborative, multidisciplinary, and creative attributes for a specific and tangible solution. (4) For creative problem-solving to improve patient experience, we should explore the possibilities of various solutions by an iterative process of divergent and convergent thinking. A concrete and visualized solution should be sought through active user interactions from various fields. For this, a specific methodology that allows users to collaborate by applying the integrative viewpoint of design thinking should be introduced.

Lomens-P0 (mixed extracts of Hordeum vulgare and Chrysanthemum zawadskii) regulate the expression of factors affecting premenstrual syndrome symptoms.

BACKGROUND/OBJECTIVES: Premenstrual syndrome (PMS) is a disorder characterized by repeated emotional, behavioral, and physical symptoms before menstruation, and the exact cause and mechanism are uncertain. Hyperprolactinemia interferes with the normal production of estrogen and progesterone, leading to PMS symptoms. Thus, we judged that the inhibition of prolactin hypersecretion could mitigate PMS symptoms. MATERIALS/METHODS: Hordeum vulgare L. extract (HVE), Chrysanthemum zawadskii var. latilobum extract (CZE), and Lomens-P0 the mixture of these extracts were tested in subsequent experiments. The effect of extracts on prolactin secretion at the in vitro level was measured in GH3 cells. Nitric oxide and pro-inflammatory mediator expression were measured in RAW 264.7 cells to confirm the anti-inflammatory effect. Also, the hyperprolactinemic Institute for Cancer Research (ICR) mice model was used to measure extract effects on prolactin and hormone secretion and uterine inflammation. RESULTS: Anti-inflammatory effects of and prolactin secretion suppress by HVE and CZE were confirmed through in vitro experiments (P < 0.05). Treatment with Lomens-P0 inhibited prolactin secretion (P < 0.05) and restored normal sex hormone secretion in the hyperprolactinemia mice model. In addition, extracts significantly inhibited the expression of pro-inflammatory biomarkers, including interleukin-1ß, and -6, tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2 (P < 0.01). We used high-performance liquid chromatography analyses to identify tricin and chlorogenic acid as the respective components of HVE and CZE that inhibit prolactin secretion. The Lomens-P0, which includes tricin and chlorogenic acid, is expected to be effective in improving PMS symptoms in the human body. CONCLUSIONS: The Lomens-P0 suppressed the prolactin secretion in hyperprolactinemia mice, normalized the sex hormone imbalance, and significantly suppressed the expression of inflammatory markers in uterine tissue. This study suggests that Lomens-P0 may have the potential to prevent or remedy materials to PMS symptoms.

Tumor-Targeted ZW800-1 Analog for Enhanced Tumor Imaging and Photothermal Therapy.

ZW800-1, a representative zwitterionic near-infrared (NIR) fluorophore, can minimize background tissue uptake owing to its balanced surface charges, and therefore, is widely used for improved NIR fluorescence imaging. As ZW800-1 has no tumor targetability, tumor imaging is highly dependent on the ability of the molecules conjugated to the ZW800-1. To enable tumor targeting using ZW800-1 without additional conjugation, we developed a tumor-targetable and renal-clearable ZW800-1 analog (ZW800-AM) based on the structural modification of ZW800-1. Specifically, an amine group on the center linker of the ZW800-1 indocyanine backbone was modified by replacing phenoxypropionic acid with tyramine linkage on the meso-chlorine atom. This modification improved the tumor targeting ability, which is known as the structure-inherent targeting strategy. More importantly, ZW800-AM not only showed sufficient tumor accumulation without nonspecific uptake but also produced a photothermal effect, killing tumor cells under 808 nm NIR laser irradiation. In addition, ZW800-AM exhibited rapid renal elimination from the body within 4 h of injection, similar to ZW800-1. Overall, the discovery of ZW800-AM as a bifunctional phototherapeutic agent may provide an ideal alternative for tumor-targeted imaging and phototherapy.

Rapid Tumor Targeting of Renal-Clearable ZW800-1 Conjugate for Efficient Photothermal Cancer Therapy.

The combination of near-infrared (NIR) fluorophores and photothermal therapy (PTT) provides a new opportunity for safe and effective cancer treatment. However, the precise molecular design of functional NIR fluorophores with desired properties, such as high tumor targetability and low nonspecific uptake, remains challenging. In this study, a renal-clearable NIR fluorophore conjugate with high tumor targetability was developed for efficient photothermal cancer therapy. The isoniazid (INH)-ZW800-1 conjugate (INH-ZW) was synthesized by conjugating an antibiotic drug, INH, with a well-known zwitterionic NIR fluorophore, ZW800-1, to improve in vivo performance and fluorescence-guided cancer phototherapy. INH-ZW not only showed rapid tumor accumulation without nonspecific tissue/organ uptake within 1 h after the injection but also generated thermal energy to induce cancer cell death under NIR laser irradiation. Compared with previously reported ZW800-1 conjugates, INH-ZW preserved the ideal biodistribution of ZW800-1 and facilitated improved tumor targeting and PTT. Together, these results demonstrate that the INH-ZW conjugate has great potential to serve as an effective PTT agent capable of rapid tumor targeting and high renal clearance, with excellent photothermal efficacy.

Bioinspired Camellia japonica carbon dots with high near-infrared absorbance for efficient photothermal cancer therapy.

Since carbon dots (CDs) exhibit excellent biocompatibility, low cytotoxicity, near-infrared (NIR) absorbance, and superior photostability, many types of CDs are considered as powerful candidates for photothermal therapy (PTT) applications. However, the development of a desirable CD is still difficult due to insufficient photothermal conversion, thus resulting in the use of high laser power densities at a high dose of CDs for the PTT effect. Herein, bioinspired sulfur-doped CDs (S-CDs) with strong NIR absorbance were prepared from Camellia japonica flowers via a facile hydrothermal method for enhancing the photothermal conversion efficiency. The as-prepared S-CDs exhibited various advantages including cost-effective preparation, good water-solubility, high biocompatibility, intense NIR absorption, and excellent photothermal effect with robust photostability. Most importantly, the optimal low dose of S-CDs (45 µg mL-1) successfully led to efficient PTT performance with a high photothermal conversion efficiency (55.4%) under moderate laser power (808 nm, 1.1 W cm-2) for safe and effective cancer therapy.

Coffee Consumption and Incident Tachyarrhythmias: Reported Behavior, Mendelian Randomization, and Their Interactions.

Importance: The notion that caffeine increases the risk of cardiac arrhythmias is common. However, evidence that the consumption of caffeinated products increases the risk of arrhythmias remains poorly substantiated. Objective: To assess the association between consumption of common caffeinated products and the risk of arrhythmias. Design, Setting, and Participants: This prospective cohort study analyzed longitudinal data from the UK Biobank between January 1, 2006, and December 31, 2018. After exclusion criteria were applied, 386 258 individuals were available for analyses. Exposures: Daily coffee intake and genetic polymorphisms that affect caffeine metabolism. Main Outcomes and Measures: Any cardiac arrhythmia, including atrial fibrillation or flutter, supraventricular tachycardia, ventricular tachycardia, premature atrial complexes, and premature ventricular complexes. Results: A total of 386 258 individuals (mean [SD] age, 56 [8] years; 52.3% female) were assessed. During a mean (SD) follow-up of 4.5 (3.1) years, 16 979 participants developed an incident arrhythmia. After adjustment for demographic characteristics, comorbid conditions, and lifestyle habits, each additional cup of habitual coffee consumed was associated with a 3% lower risk of incident arrhythmia (hazard ratio [HR], 0.97; 95% CI, 0.96-0.98; P < .001). In analyses of each arrhythmia alone, statistically significant associations exhibiting a similar magnitude were observed for atrial fibrillation and/or flutter (HR, 0.97; 95% CI, 0.96-0.98; P < .001) and supraventricular tachycardia (HR, 0.96; 95% CI, 0.94-0.99; P = .002). Two distinct interaction analyses, one using a caffeine metabolism-related polygenic score of 7 genetic polymorphisms and another restricted to CYP1A2 rs762551 alone, did not reveal any evidence of effect modification. A mendelian randomization study that used these same genetic variants revealed no significant association between underlying propensities to differing caffeine metabolism and the risk of incident arrhythmia. Conclusions and Relevance: In this prospective cohort study, greater amounts of habitual coffee consumption were associated with a lower risk of arrhythmia, with no evidence that genetically mediated caffeine metabolism affected that association. Mendelian randomization failed to provide evidence that caffeine consumption was associated with arrhythmias.

Indocyanine Green and Methyl-ß-Cyclodextrin Complex for Enhanced Photothermal Cancer Therapy.

A feasible and biocompatible supramolecular complex self-assembled from indocyanine green (ICG) and methyl-ß-cyclodextrin (Mß-CD) was developed for targeted cancer imaging, which enhanced fluorescence-guided photothermal cancer therapy. This study confirmed that the formation of an inclusion complex of the heterocyclic ICG moiety and Mß-CD inner cavity could result in improved tumor targetability compared with free ICG. The ICG-CD complex could be used as a bifunctional phototherapeutic agent for targeted cancer phototherapy due to the high tumor targetability of the Mß-CD moiety and effective photothermal performance of the near-infrared (NIR) ICG moiety. Upon NIR laser irradiation, the photothermal effect exerted by the ICG-CD complex significantly enhanced the temperature at the tumor site by 56.2 °C within 5 min. Targeting HT-29 tumors using the ICG-CD complex resulted in an apparent reduction in tumor volumes over the 9 days after photothermal treatment. Moreover, no tumor recurrence or body weight loss were observed after administering a single dose of ICG-CD complex with NIR laser irradiation. Therefore, the administration of the biocompatible ICG-CD complex in combination with NIR laser treatment can be safely explored as a potential strategy for future clinical applications.

Tumor-targeted near-infrared fluorophore for fluorescence-guided phototherapy.

A tumor-targeted near-infrared (NIR) fluorophore CA800SO3 was developed for fluorescence-guided phototherapy. This new type of NIR fluorophore showed high tumor targetability based on the structure-inherent targeting approach. This fluorophore generated sufficient hyperthermia and reactive oxygen species (ROS) simultaneously for synergistic cancer phototherapy, induced by an 808 nm laser irradiation.

Detection of high-frequency artifact as a function of pulse generator algorithms and outer-insulation material.

BACKGROUND: A high rate of malfunction, predominantly intermittent high-frequency artifacts (HFAs), has been recently reported in Abbott Medical Tendril pacing leads. OBJECTIVE: To investigate the factors associated with the occurrence of HFAs on Tendril leads using a commonly used comparator lead for a control. METHODS: We reviewed institutional data for Medtronic CapSureFix 5076 and Abbott Medical Tendril pace-sense leads retrospectively. Recordings deemed to be due to electromagnetic interference and far-field oversensing were not included in the classification of HFAs. RESULTS: A total of 7673 leads were analyzed: 1628 Optim-insulated Tendril leads, 825 non-Optim Tendril leads, and 5220 CapSureFix 5076. HFAs were seen in 212 leads and were more frequently observed in Tendril compared to CapSureFix leads during a mean follow-up of 4.1 ± 3.6 years. Lower age at implant, defibrillator systems, atrial position, and connection to an Abbott Medical generator were associated with increased HFA. In multivariable analysis, only connection to Abbott Medical generators (odds ratio 7.686, P < .001) and age (odds ratio 0.988 per year, P = .016) were independently associated with HFAs on pace-sense leads. In an Abbott-generator-only analysis, Optim-insulated Tendril leads were more likely to display HFAs than non-Optim Tendril leads but not Medtronic CapSureFix 5076 leads. CONCLUSION: Abbott Medical pulse generators independently predict HFA in Tendril and CapSureFix 5076 leads, likely the result of displaying short or low-amplitude noise episodes that other devices do not record. When restricted to Abbott generators only, Optim-insulated Tendril leads show an increased incidence of HFAs when compared to non-Optim Tendril leads but not CapSureFix 5076 leads.

Anti-inflammatory activity of the decoction of Forsythia suspensa (Thunb.) Vahl is related to Nrf2 and A20.

ETHNOPHARMACOLOGICAL RELEVANCE: The water extract of Forsythiae Fructus (WFF) is an herbal remedy that is prescribed to treat various inflammatory diseases in traditional Chinese medicine. Although the anti-inflammatory activity of WFF has been reported, the underlying mechanisms for the activity remain unclear. Here, we examined whether the anti-inflammatory activity of WFF is associated with Nrf2, an anti-inflammatory factor, and A20, an ubiquitin-regulator protein that inhibits signaling cascades of endotoxin or cytokines. MATERIALS AND METHODS: The water extract of Forsythia suspensa (Thunb.) Vahl was prepared and fingerprinted by HPLC. Cytotoxicity and intracellular ROS induced by WFF were determined by MTT and FACS analyses, respectively. Nuclear and cytoplasmic proteins were analyzed by immunoblot. Expression of mRNA was analyzed by a semi-quantitative RT-PCR. Expression of proteins or genes was quantitated by Image J. RESULTS: WFF activated Nrf2, inducing the expression of Nrf2-dependent genes, such as HO-1, NQO1, and GCLC in RAW 264.7 cells. On the other hand, WFF suppressed NF-κB induced by LPS or TNF-α, which was coincided with the expression of A20. Conversely, WFF failed to suppress NF-κB when A20 expression was silenced by siRNA. CONCLUSION: WFF activated Nrf2 and expressed A20. Given that Nrf2 suppresses inflammation and A20 broadly disrupts inflammatory signaling cascades, our results suggest that the anti-inflammatory activity of WFF is attributable to Nrf2 and A20.

The complete chloroplast genome of Codonopsis lanceolata (Campanulaceae).

The complete chloroplast genome sequence of Codonopsis lanceolata was determined by next generation sequencing. The total length of chloroplast genome of C. lanceolata was 169,447 bp long, including a large single-copy (LSC) region of 85,253 bp, a small single-copy (SSC) region of 8060 bp, and a pair of identical inverted repeat regions (IRs) of 38,067 bp. A total of 110 genes was annotated, resulting in 79 protein-coding genes, 27 tRNA genes, and 4 rRNA genes. The phylogenetic analysis of C. lanceolata with related chloroplast genome sequences in this study provided the taxonomical relationship of C. lanceolata in the genus Campanula.

Anesthetic protocol for microinjection-related handling of Siberian sturgeon (Acipenser baerii; Acipenseriformes) prolarvae.

An anesthetic protocol was optimized for microinjection-related handling of Siberian sturgeon (Acipenser baerii; Acipenseriformes) prolarvae, an extant primitive fish species commonly grown in aquaculture. Comparative examinations of three selected anesthetics (clove oil, lidocaine, and MS-222) with a dosage regime of 50, 100, 200, and 400 mg/L indicated that MS-222 was the most efficient agent for Siberian sturgeon prolarvae, as evidenced by the fast induction of anesthesia with quick and uniform recovery. Meanwhile, clove oil should be avoided, due to prolonged recovery times varying widely between individuals. None of the tested anesthetics significantly affected prolarval viability at any of the dosage regimes tested in this study. Based on an analysis of the duration of an unconscious state in air, we recommend a dose of 200 mg/L MS-222 for microinjection. Recovery time after use of this dose was influenced by the prolarval age and the development of gills, in which prolarvae older than 3 days after hatching required longer recovery times than did younger prolarvae. Post-recovery behavioral assessment showed no apparent difference between MS-222-anesthetized and non-anesthetized prolarvae in their swimming behavior and phototactic responses. Applicability of currently developed anesthetic protocol using MS-222 in larval microinjection was demonstrated with the injection of a visible dye to the anesthetized prolarvae, followed by the analysis of post-recovery viability. Taken together, the present anesthetic protocol based on 200 mg/L of MS-222 could provide researchers with practical usefulness with good safety margins for the micromanipulation and other related handlings of Siberian sturgeon prolarvae.

An Oriental Medicine, Hyungbangpaedok-San Attenuates Motor Paralysis in an Experimental Model of Multiple Sclerosis by Regulating the T Cell Response.

The preventive and therapeutic mechanisms in multiple sclerosis are not clearly understood. We investigated whether Hyungbangpaedok-san (HBPDS), a traditional herbal medicine, has a beneficial effect in experimental autoimmune encephalomyelitis (EAE) mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG 35-55). Onset-treatment with 4 types of HBPDS (extracted using distilled water and 30%/70%/100% ethanol as the solvent) alleviated neurological signs, and HBPDS extracted within 30% ethanol (henceforth called HBPDS) was more effective. Onset-treatment with HBPDS reduced demyelination and the recruitment/infiltration and activation of microglia/macrophages in the spinal cord of EAE mice, which corresponded to the reduced mRNA expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß), iNOS, and chemokines (MCP-1, MIP-1α, and RANTES) in the spinal cord. Onset-treatment with HBPDS inhibited changes in the components of the blood-brain barrier such as astrocytes, adhesion molecules (ICAM-1 and VCAM-1), and junctional molecules (claudin-3, claudin-5, and zona occludens-1) in the spinal cord of EAE mice. Onset-treatment with HBPDS reduced the elevated population of CD4+, CD4+/IFN-γ+, and CD4+/IL-17+ T cells in the spinal cord of EAE mice but it further increased the elevated population of CD4+/CD25+/Foxp3+ and CD4+/Foxp3+/Helios+ T cells. Pre-, onset-, post-, but not peak-treatment, with HBPDS had a beneficial effect on behavioral impairment in EAE mice. Taken together, HBPDS could alleviate the development/progression of EAE by regulating the recruitment/infiltration and activation of microglia and peripheral immune cells (macrophages, Th1, Th17, and Treg cells) in the spinal cord. These findings could help to develop protective strategies using HBPDS in the treatment of autoimmune disorders including multiple sclerosis.

LC-MS/MS method for determination of hederacolchiside E, a neuroactive saponin from Pulsatilla koreana extract in rat plasma for pharmacokinetic study.

A simple, rapid, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was applied to pharmacokinetic study of a neuroactive oleanolic-glycoside saponin, hederacolchiside E from SK-PC-B70M, a standardized extract of Pulsatilla koreana in rat. Rat plasma samples were pretreated by protein precipitation with acetonitrile, eluted from C(18) column, and analyzed using electrospray ionization (ESI)-MS/MS in negative ion mode. Digoxin was used as an internal standard. The standard curves were linear (r>0.997) over the concentration ranges of 2-500 ng/mL. The intra- and inter-day precisions were measured to be below 9% and accuracy between 90 and 111% for all quality control samples at 2, 20, 100, and 500 ng/mL (n=5). The lower limits of quantification (LLOQ) for hederacolchiside E was 2 ng/mL and the limit of detection (LOD) 0.5 ng/mL using 20 microL of plasma sample. Subsequently, hederacolchiside E was determined in rat plasma samples after oral administration of SK-PC-B70M. The mean maximum plasma concentrations of hederacolchiside E were 0.07, 0.13, and 0.36 microg/mL and the mean areas under the plasma concentration versus time curve 0.56, 1.27, and 6.46 microg h/mL at doses of 100, 200, and 400 mg/kg, respectively, which indicated non-linear pharmacokinetic pattern. In conclusion, this method was successfully applied to the pharmacokinetic study of hederacolchiside E after an oral administration of SK-PC-B70M to rats.

Combined effects of bovine colostrum and glutamine in diclofenac-induced bacterial translocation in rat.

BACKGROUND AND AIMS: The aim of this study was to examine whether the combined administration of bovine colostrum and glutamine was able to prevent the non-steroidal anti-inflammatory drug (NSAID)-induced gut damage and bacterial translocation (BT) in the rats. METHODS: The animal model population of the study consisted of six groups; control group, diclofenac group, diclofenac with milk group, diclofenac with colostrum group, diclofenac with glutamine group and diclofenac with colostrum and glutamine group. The animals with milk, colostrum or glutamine were fed with low fat milk, liquid colostrum or glutamine by orogastric gavage for 5 days before the diclofenac administration. Intestinal permeability, serum biochemical profiles and intestinal adhesion for assessment of the gut damage, and enteric bacterial overgrowth and BT at the mesenteric lymph nodes, liver, spleen and systemic blood were measured. RESULTS: Diclofenac caused the increase in gut damage, enteric bacterial numbers and BT. Supplements with colostrum or glutamine reduced these changes induced by diclofenac, but this result was not seen for supplementation with low fat milk. Combined administration of colostrum and glutamine reduced diclofenac-induced gut damage and BT as compared to the use of bovine colostrum alone or glutamine alone. CONCLUSIONS: This study suggested that the combined administration of bovine colostrum and glutamine might effectively reduce NSAID-induced gut damage and BT in the rat.

Protective effects of bovine colostrum on non-steroidal anti-inflammatory drug induced intestinal damage in rats.

The aim of this study was to examine whether bovine colostrum was able to prevent the NSAID induced small intestinal damage in animals. The animal model population of the study consisted of 4 groups: control group, diclofenac group, diclofenac with 10% low fat milk group and diclofenac with 5% colostrum group. The animals with milk or colostrum were fed with 10% low fat milk or 5% colostral solution for 5 days before the administration of diclofenac. Gut injuries were induced by administration of a single dose of diclofenac (100 mg/kg orally). Epithelial permeability values (24 hour urinary excretion of 51Cr-ethylenediaminetetraacetic acid [51Cr-EDTA]), enteric aerobic bacterial counts, serum biochemical profiles and pathologic findings of distal ileum were measured. Diclofenac caused a marked increase in the intestinal permeability, enteric bacterial numbers and intestinal villous damage, and enteric protein and albumin loss. Combined administration of bovine colostrum reduced the increase in intestinal permeability, enteric bacterial overgrowth, protein losing enteropathy and mucosal villous damage of the small intestine induced by diclofenac. Bovine colostrum may have a beneficial effect in prevention of NSAID induced small intestinal injuries.