Search

Background. Allergic rhinitis (AR) is a common disease, and conventional medications are often insufficient for treatment. Bojungikgi-tang (BJIGT) is an herbal medicine widely used in traditional medicine and has anti-inflammatory and immunoregulatory effects. We hypothesize that BJIGT would improve nasal symptoms in patients with persistent AR (PAR). Methods. This is a randomized, double-blind, placebo-controlled, phase II trial. A total of 105 patients, identified with perennial allergens, with a history of PAR and a mean total nasal symptom score (TNSS) ≥ 5 during the run-in period will be recruited from Daejeon Korean Medicine Hospital. Participants will be randomly assigned to a high-dose BJIGT group, standard-dose BJIGT group, or control group (placebo) in a 1 : 1 : 1 allocation ratio after a week run-in period. The treatment medication will be taken three times per day for 4 weeks. The primary outcome measure is the mean change in the TNSS before and after medication. The secondary outcome measures include the Korean Allergic Rhinitis-Specific Quality of Life Questionnaire, total IgE and eosinophil count, overall assessment of AR, pattern identification questionnaire for AR, and Sasang constitution. Discussion. The aim of this study is to investigate the efficacy and safety of BJIGT in the treatment of PAR and to determine the suitable dosage of BJIGT. Therefore, we planned a randomized, controlled, phase II trial of two different doses of BJIGT compared with placebo, and the results of this study are expected to provide evidence for the use of BJIGT as a treatment of PAR. Trial Registration. The National Clinical Trial Registry Clinical Research Information Service, CRIS, KCT0006616, https://cris.nih.go.kr/cris/search/detailSearch.do/20706. [ABSTRACT FROM AUTHOR]

Background: Radiation pneumonitis is a common and serious complication of radiotherapy. Many published randomized controlled studies (RCTs) reveal a growing trend of using herbal medicines as adjuvant therapy to prevent radiation pneumonitis; however, their efficacy and safety remain unexplored. Objective: The aim of this systematic review is to evaluate the efficacy and safety of herbal medicines as adjunctive therapy for the prevention of radiation pneumonitis in patients with lung cancer who undergo radiotherapy. Methods: We searched the following 11 databases: three English medical databases [MEDLINE (PubMed), EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL)], five Korean medical databases (Korean Studies Information, Research information Service System, KoreaMed, DBPIA, National Digital Science Library), and three Chinese medical databases [the China National Knowledge Database (CNKI), Journal Integration Platform (VIP), and WanFang Database]. The primary outcome was the incidence of radiation pneumonitis. The risk of bias was assessed using the Cochrane risk-of-bias tool. Results: Twenty-two RCTs involving 1819 participants were included. The methodological quality was poor for most of the studies. Meta-analysis showed that herbal medicines combined with radiotherapy significantly reduced the incidence of radiation pneumonitis (n = 1819; RR 0.53, 95% CI 0.45–0.63, I2 = 8%) and the incidence of severe radiation pneumonitis (n = 903; RR 0.22, 95% CI 0.11–0.41, I2 = 0%). Combined therapy also improved the Karnofsky performance score (n = 420; WMD 4.62, 95% CI 1.05–8.18, I2 = 82%). Conclusion: There is some encouraging evidence that oral administration of herbal medicines combined with radiotherapy may benefit patients with lung cancer by preventing or minimizing radiation pneumonitis. However, due to the poor methodological quality of the identified studies, definitive conclusion could not be drawn. To confirm the merits of this approach, further rigorously designed large scale trials are warranted. [ABSTRACT FROM AUTHOR]

Scrotal hyperthermia leads to oxidative stress and apoptosis in spermatogenic cells, which subsequently causes male infertility. In this study, we examined the effects of β-carotene and/or curcumin on heat-stress- (HS-) induced testicular injuries in mice. ICR male mice (8 weeks old) were consecutively treated with β-carotene (10 mg/kg) and/or curcumin (20 mg/kg) orally once a day for 14 days and then subjected to single exposure with scrotal HS at 43°C for 15 min on day 7. HS induced a significant reduction in testicular weight, appearance of multinucleated giant cells, and desquamation of germ cells in destructive seminiferous tubules, as well as degenerative Leydig cells. Moreover, HS reduced the superoxide dismutase (SOD) activity and mRNA levels of mitochondrial SOD, phospholipid hydroperoxide glutathione peroxidase, B-cell lymphoma-extra-large, and 3β-hydroxysteroid dehydrogenase, with increases in lipid peroxidation levels and mRNA levels of BCL2-associated X protein and caspase-3 relative to those of the control group. However, these changes were significantly recovered by combined treatment with β-carotene and curcumin after HS. These findings indicate that the combined treatment with β-carotene and curcumin might be a valuable protective agent to ameliorate hyperthermic spermatogenic disorders via its potent antioxidative, antiapoptotic, and androgen synthetic effects. [ABSTRACT FROM AUTHOR]

Introduction: Posterior cruciate ligament (PCL) injuries and direct injury-related patellar fractures have similar causative factors. However, the mechanisms underlying these injuries differ. We aimed to evaluate the incidence and relationship between PCL injuries and direct injury-related patellar fractures. Materials and Methods: Of the 195 patients diagnosed with a patellar fracture at our clinic during 2007-2011, 104 required surgical treatment and underwent the posterior drawer test under general anesthesia and magnetic resonance imaging. We assessed whether the causes of trauma, fracture classification, compression of the fracture fragment, and fracture displacement were related to the incidence of PCL injuries. Results: Of the 104 patients, 26 had concomitant PCL injuries with direct injury-related patellar fractures. Most of the PCL injuries were grades 1 and 2, observed in 14 and 9 patients, respectively. Among three patients with grade 3 PCL injury, only two required PCL reconstruction. No significant relationship was observed between the causes of trauma and the incidence of PCL injury. According to the fracture classification, lower pole and comminuted fractures were associated with higher incidence rates of PCL injury than transverse and vertical fractures. Compressed and displaced patellar fractures were also associated with higher incidence rates of PCL injury. Conclusion: Although a PCL injury requiring surgical intervention was extremely rare, 25 % patients who required surgery for patellar fractures presented with a PCL injury. The incidence of a PCL injury was higher in the lower pole, comminuted, displaced, and compressed patellar fractures. [ABSTRACT FROM AUTHOR]

Menkes disease is a very rare X-linked copper metabolism disorder that results from an ATP7A gene mutation. With the advent of subcutaneous copper-histidine therapy, the early diagnosis of Menkes disease becomes of utmost importance for patients' prognosis. In the present study, the clinical characteristics of 12 Korean patients with Menkes disease (11 males and 1 female from 11 unrelated families) were described along with the mutation spectrum. Only 2 male patients were diagnosed in the neonatal period, and the other male patients were diagnosed at age 4.3 ± 1.9 months. The presenting signs included depigmented kinky hair, neurologic deficits, and hypotonia. Serum copper and ceruloplasmin levels were markedly decreased. Intracranial vessels were dilated with tortuosity and accompanied by regional cerebral infarctions, even at an early age. Of note, the female patient was diagnosed at age 18 months, during the evaluation for developmental delay, by characteristic MRA findings, biochemical profiles, and genetic evaluation. A total of 11 ATP7A mutations were identified, including five previously unreported mutations. Most mutations were truncated (except 1 missense mutation), including 3 frameshift, 2 nonsense, 3 large deletion, and 2 splice-site variants. The age at commencement of copper-histidine treatment was variable among patients age 7.3 ± 7.5 (0.5-27) months. Despite the treatment, seven patients died before age 5 years, and the remaining patients were severely retarded in neurodevelopment. The poor outcomes of our patients might be related to delayed therapy, but severe ATP7A mutations should be noted as well. [ABSTRACT FROM AUTHOR]

Purpose: Wrist fracture is considered a typical initiating trauma for complex regional pain syndrome type I (CRPS I). However, few studies have comprehensively evaluated factors associated with the occurrence of CRPS I after the surgical treatment of a distal radius fracture (DRF). This study evaluates the factors influencing the occurrence of CRPS I after the surgical treatment of a DRF. Methods: A total of 477 patients with a DRF who had been treated surgically were enrolled in this prospective observational study. Patients were followed for 6 months after surgery, and CRPS I was diagnosed using the Budapest diagnostic criteria for research. The factors assessed for the development of CPRS I were age, gender, the body mass index, the type of fracture, the energy of trauma, the number of trial reductions, the type of surgery, and the duration of immobilization. A multivariate logistic regression analysis was conducted to identify independent predictors of the occurrence of CRPS I. Results: Among the 477 patients, 42 (8.8 %) satisfied the Budapest criteria for CRPS I within 6 months of surgery. Female patients developed CRPS I more frequently, and the patients who developed CRPS I were older and more likely to sustain a high energy injury or have a comminuted fracture. According to the multivariate analysis, female patients and those with a high energy trauma or severe fracture type were significantly more likely to develop CRPS I ( p = 0.02, 0.01, and 0.01, respectively). Conclusions: High energy injuries, severe fractures, and the female gender contribute to the development of CRPS I after the surgical treatment of DRF. The results have important implications for physicians who wish to identify patients at high risk for CRPS I after operative fixation for DRF and instigate treatment accordingly. [ABSTRACT FROM AUTHOR]

In randomized controlled trials (RCTs), the most compelling need is to determine whether the treatment condition was more effective than control. However, it is generally recognized that not all participants in the treatment group of most clinical trials benefit equally. While subgroup analyses are often used to compare treatment effectiveness across pre-determined subgroups categorized by patient characteristics, methods to empirically identify naturally occurring clusters of persons who benefit most from the treatment group have rarely been implemented. This article provides a modeling framework to accomplish this important task. Utilizing information about individuals from the treatment group who had poor outcomes, the present study proposes an a priori clustering strategy that classifies the individuals with initially good outcomes in the treatment group into: (a) group GE (good outcome, effective), the latent subgroup of individuals for whom the treatment is likely to be effective and (b) group GI (good outcome, ineffective), the latent subgroup of individuals for whom the treatment is not likely to be effective. The method is illustrated through a re-analysis of a publically available data set from the National Institute on Drug Abuse. The RCT examines the effectiveness of motivational enhancement therapy from 461 outpatients with substance abuse problems. The proposed method identified latent subgroups GE and GI, and the comparison between the two groups revealed several significantly different and informative characteristics even though both subgroups had good outcomes during the immediate post-therapy period. As a diagnostic means utilizing out-of-sample forecasting performance, the present study compared the relapse rates during the long-term follow-up period for the two subgroups. As expected, group GI, composed of individuals for whom the treatment was hypothesized to be ineffective, had a significantly higher relapse rate than group GE (63% vs. 27%; χ² = 9.99, p-value = .002). [ABSTRACT FROM AUTHOR]

Background/Aims: The objective of this study was to evaluate the efficacy of recombinant human growth hormone (rhGH) therapy and the influence of genotype on the response to rhGH therapy in children with Noonan syndrome (NS). Methods: 14 male and 4 female subjects with NS with short stature, whose height was <3rd percentile, were included. The rhGH was subcutaneously administered at a dose of 66 μg/kg/day. Mutations in the PTPN11 gene were identified in 10 subjects (55.6%). Mutations in the SOS1 (2 children, 11.1%), MEK1 (1 child, 5.6%) and KRAS (1 child, 5.6%) genes were also found. Results: Height SDS increased from -2.8 ± 0.9 at the start of rhGH therapy to -2.0 ± 0.9 12 months later (p < 0.001). Height velocity increased from 5.0 ± 0.9 cm/year in the year before treatment to 8.9 ± 1.6 during treatment (p < 0.001). Changes in height SDS, height velocity, and serum IGF-1 level did not differ significantly between those children with or without PTPN11 mutations. Conclusion: The rhGH therapy significantly improved the growth velocity and increased the serum IGF-1 level. Long-term correlation between genotype and rhGH therapy responsiveness needs to be addressed in a large population. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The objective of this review is to assess the clinical evidence for or against acupressure as a treatment for neurological disorders. We searched the literature from 12 databases from their inception to July 2010. We included any type of controlled clinical trial (CCT) in which patients with neurological disorders were treated with acupressure. The methodological quality of all clinical trials was assessed using the Cochrane risk of bias analysis. In total, two randomized clinical trials (RCTs) and four CCTs were included. Four studies (one RCT and three CCTs) compared the effects of acupressure with routine care or no treatment in patients with stroke and showed significant effects of acupressure on improving patient function and symptoms. One RCT, which compared acupressure with sham acupressure and no treatment in patients with headache, also showed that acupressure significantly reduced headache severity and pain. However, all trials were open to methodological limitations and a high risk of bias. In conclusion, current evidence showing that acupressure is an effective treatment for improving function and symptoms in patients with stroke is limited. However, the evidence is insufficient to draw conclusions concerning the effects of acupressure on other neurological disorders. More rigorous studies are warranted. [ABSTRACT FROM AUTHOR]

Congenital lipoid adrenal hyperplasia (CLAH) is the most severe form of congenital adrenal hyperplasia, characterized by lack of synthesis of all gonadal and adrenal steroid hormones. Ovarian cysts can develop as complications of CLAH. However, the precise mechanism of development and natural history of such cysts in patients with CLAH have not yet been determined. We recently treated a 14-year-old female patient with CLAH and ovarian cyst torsion. As a neonate, she presented with vomiting, skin pigmentation, and electrolyte imbalance. At that time, her serum adrenocorticotropic hormone concentration was elevated, while 17-hydroxypregnenolone level was normal, as were her normal female external genitalia. Mutation analysis showed that she was homozygous for p.Q258X in the StAR gene. She underwent spontaneous puberty and menstruation. At 14 years of age, she received salpingo-oophorectomy because of ovarian cyst torsion presenting as acute pelvic pain. Ovarian cysts are important clinical manifestations in 46,XX patients with CLAH, although onset time and severity can vary depending on individuals. Thus, patients with CLAH should be carefully monitored for ovarian complications to preserve as much ovarian function as possible. [ABSTRACT FROM AUTHOR]

Purpose: Endoscopic histoacryl injection (EHI) is reported to be an effective treatment modality for bleeding gastric varices (GVs) but controversial as a prophylactic treatment for non-bleeding GVs because efficacy and safety have yet to be determined. The aim of this study was to evaluate safety and long-term outcomes of prophylactic EHI for non-bleeding GVs with a high risk of bleeding.Methods: Thirty-three patients (23 males/10 females, mean age 56.6 years old) with a high risk of gastric variceal bleeding (large tumorous (27), red color sign (14) or rapidly growing in size (1)) underwent EHI. According to the grade of GVs, 25 patients belonged to F3, seven to F2, and one to F1. In terms of the locations of GVs, four patients belonged to type IGV1, 21 to type GOV2, and eight to type GOV1.Results: Obliteration of GVs was achieved in all of the treated patients. Twenty-three patients required one session and ten needed more than two sessions to obliterate their GVs. A mean volume of histoacryl used per session was 2.0 ml. Complications related to the procedure included immediate bleeding in two patients and bacteremia in one patient. The mean duration of follow-up was 12.2 months and eradication of GVs was achieved in 21 (95%) of 22 patients who were followed-up more than 3 months. Index GVs recurred in three of 21 patients (14%) and re-bleeding in index GVs after EHI occurred in two of 26 patients (8%).Conclusions: Prophylactic EHI can be a promising procedure for eradication of non-bleeding GVs in case with a high risk of bleeding. [ABSTRACT FROM AUTHOR]

SERTAD/TRIP-Br genes are considered as a key nuclear transcriptional player in diverse mechanisms of cell including carcinogenesis. The Oncomine™-Online Platform was used for differential expression and biological insights. Kaplan-Meier survival estimated by KM-plotter/cBioPortal/PrognoScan with 95% CI. SERTAD1 was found significantly elevated levels in most of tumor samples. Kaplan-Meier Plotter results distinctly showed the SERTAD1 over-expression significantly reduced median overall-survival (OS) of patients in liver (n = 364/Logrank-test p = 0.0015), ovarian (n = 655/Logrank-test p = 0.00011) and gastric (n = 631/Logrank-test p = 0.1866). Increased level of SERTAD1 has a significantly higher survival rate in the initial time period, but after 100 months slightly reduced OS (n = 26/Logrank-test p = 0.34) and RFS in HER2 positive breast cancer patients. In meta-analysis, cancer patients with higher SERTAD1 mRNA fold resulted worse overall survival than those with lower SERTAD1 levels. Heterogeneity was observed in the fixed effect model analysis DFS [Tau2 = 0.0.073, Q (df = 4) = 15.536 (p = 0.004), I2 = 74.253], DSS [Tau2 = 1.015, Q (df = 2) = 33.214, (p = 0.000), I2 = 93.973], RFS [Tau2 = 0.492, Q (df = 7) = 71.133 (p = 0.000), I2 = 90.159] (Figure 5). OS [Tau2 = 0.480, Q (df = 17) = 222.344 (p = 0.000), I2 = 92.354]. Lastly, SERTAD1 involved in several signaling cascades through interaction and correlation with many candidate factors as well as miRNAs. This meta-analysis demonstrates a robust evidence of an association between higher or lower SERTAD1, alteration and without alteration of SERTAD1 in cancers in terms of survival and cancer invasiveness. [ABSTRACT FROM AUTHOR]

Background: Tumor heterogeneity and evolutionary complexity may underlie treatment failure in spite of the development of many targeted agents. We suggest a novel strategy termed induced phenotype targeted therapy (IPTT) to simplify complicated targets because of tumor heterogeneity and overcome tumor evolutionary complexity. Methods: We designed a caspase-3 specific activatable prodrug, DEVD-S-DOX, containing doxorubicin linked to a peptide moiety (DEVD) cleavable by caspase-3 upon apoptosis. To induce apoptosis locally in the tumor, we used a gamma knife, which can irradiate a very small, defined target area. The in vivo antitumor activity of the caspase-3–specific activatable prodrug combined with radiation was investigated in C3H/HeN tumor-bearing mice (n = 5 per group) and analyzed with the Student’s t test or Mann-Whitney U test. All statistical tests were two-sided. We confirmed the basic principle using a caspase-sensitive nanoprobe (Apo-NP). Results: A single exposure of radiation was able to induce apoptosis in a small, defined region of the tumor, resulting in expression of caspase-3. Caspase-3 cleaved DEVD and activated the prodrug. The released free DOX further activated DEVD-S-DOX by exerting cytotoxic effects on neighboring tumor or supporting cells, which repetitively induced the expression of caspase-3 and the activation of DEVD-S-DOX. This sequential and repetitive process propagated the induction of apoptosis. This novel therapeutic strategy showed not only high efficacy in inhibiting tumor growth (14-day tumor volume [mm3] vs radiation alone: 848.21±143.24 vs 2511.50±441.89, P < .01) but also low toxicity to normal cells and tissues. Conclusion: Such a phenotype induction strategy represents a conceptually novel approach to overcome tumor heterogeneity and complexity as well as to substantially improve current conventional chemoradiotherapy with fewer sequelae and side effects. [ABSTRACT FROM PUBLISHER]

Due to the instability of esomeprazole magnesium dihydrate (EPM), a proton pump inhibitor, in gastric fluid, enteric-coated dosage form is commonly used for therapeutic application. In this study, we prepared new gastric fluid resistant solid dispersions (SDs) containing alkalizers. Then, new mechanistic evidence regarding the effects of pharmaceutical alkalizers on the aqueous stability of EPM in simulated gastric fluid was investigated. The alkalizer-loaded SD were prepared by dissolving or dispersing EPM, hydroxypropyl methylcellulose (HPMC) 6 cps, and an alkalizer, in ethanol 50% (v/v) followed by spray drying. Nine different alkalizers were assessed for in vitro stability in two media, simulated gastric fluid (pH 1.2 buffer) and simulated intestinal fluid (pH 6.8 buffer). The microenvironmental pH (pH M ) was measured to evaluate the effect of the alkalizer on the pH M of SDs. Drug crystallinity and morphology of the SDs were also examined by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The interactions among EPM, the polymer, and the alkalizer were elucidated by Fourier transform infrared (FTIR) spectroscopy. The in vivo absorption studies of the optimized alkalizer-containing SD and the enteric-coated reference tablet Nexium ® were then conducted in beagle dogs. Among alkalizers, MgO loaded in SDs proved to be the best alkalizer to stabilize EPM in simulated gastric fluid. pH M values of the alkalizer-containing SDs were significantly higher than that of the SD without alkalizer. The pH M values decreased in the following order: MgO, Na 2 CO 3 , Ca(OH) 2 , and no alkalizer. DSC and PXRD data exhibited a change in the drug crystallinity of the SDs from crystalline to amorphous form. SEM data showed a relatively spherical shape of the MgO-loaded SD compared to the less-defined shape of pure drug. FTIR indicated a strong molecular interaction among EPM, alkalizer and polymer; in particular, MgO showed the strongest interaction with EPM. It was evident that alkalizer interacts with benzimidazole ring and/or sulfonyl group of EPM for enhancing EPM stability in gastric fluid. Regarding the in vivo absorption studies in beagle dogs, the optimized SD (C16) was bioequivalent to the reference Nexium ® and had a considerable greater absorption at the early stages. The current alkalizer-containing SD could provide a promising approach for aqueous stabilization of acid-labile drugs without using enteric coating method. [ABSTRACT FROM AUTHOR]

Abstract: Recently, we synthesized novel amphiphilic gelatin–oleic acid (GO) conjugate to prepare self-assembled nanoparticles for drug delivery. The aim of this study was to investigate pharmaceutical potentialities of self-assembled GO nanoparticles for solubility enhancement and modified release of poorly water-soluble drugs. Three poorly water-soluble model drugs with different pH-dependent solubility (valsartan and aceclofenac, insoluble at pH 1.2; telmisartan, insoluble at pH 6.8) were chosen to investigate the potential contributions of self-assembled GO nanoparticles to solubility enhancement and controlled release. The particle size of the drug-loaded nanoparticles was 200–250nm. Zeta potential was calculated, and instrumental analysis such as powder X-ray diffraction (PXRD) and Fourier transform infrared (FT-IR) spectroscopy were used to investigate the physicochemical properties of the drug-loaded nanoparticles. Compared to the drug alone, the drug-loaded nanoparticles showed enhanced solubility. Furthermore, the release profiles of the model drugs were modified in a controlled manner. The current self-assembled GO nanoparticles can provide a versatile potential in drug delivery and tumor targeting. [Copyright &y& Elsevier]

A major hurdle in cancer treatment is the precise targeting of drugs to the cancer site. As many cancer cells overexpress the transferrin receptor (TfR), the transferrin (Tf)-TfR interaction is widely exploited to target cancer cells. In this study, novel amphiphilic apo-Tf stearic acid (TfS) conjugates were prepared and characterized by Fourier transform infrared (FTIR) spectroscopy, matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry, and trinitrobenzenesulfonic acid (TNBS) assay. The prepared TfS conjugates were readily self-assembled in water to form nanoparticles (NPs), consisting of TfS as a core of NPs, whose sizes and zeta potentials were determined by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and a particle size analyzer. Hydrophilic water-soluble doxorubicin (DOX) was chosen as a model drug. DOX-loaded TfS NPs (NP + DOX), prepared by the adsorption of DOX on the NP surface via the incubation method, were analyzed for their cell targeting and killing efficiencies in TfR-overexpressing A549 and HCT116 cell lines by MTT assay, confocal microscopy, and fluorescence assisted cell sorting (flow cytometry). The data showed that NP + DOX exhibited improved cancer cell targeting and killing properties compared to that reported for free DOX. Further, the cytotoxic efficiency of NP + DOX was comparable to that of PEGylated liposomal product, Doxil ® , while its cellular uptake was higher than that of Doxil ® . Thus, this novel receptor-based TfS NP drug delivery system has great potential to target TfR-overexpressing cancer cells without off-target effects. [ABSTRACT FROM AUTHOR]

A new conceptual nanoparticle consisting of a silica-coated iron oxide magnetic core and a fattigation-based biocompatible shell with oleic acid and hydrophilic protein (gelatin). The prepared particle can be a useful theranostics platform material for diagnostic imaging and as a drug delivery system. Oleic acid and gelatin were conjugated on the silica-coated magnetic nanoparticle surface to provide three primary functionalities: 1) enhancing biocompatibility and solubility in aqueous solution and providing the ability to incorporate hydrophobic chemical drugs into the shell for delivery, 2) improving treatment-response magnetic monitoring as a diagnostic agent with low nanotoxicity, and 3) increasing anticancer efficacy owing to the controlled release of the incorporated drug in cells and in an animal model. We prepared magnetic-silica nanoparticles with super-paramagnetic properties, which are utilized as a T 2 -weighted magnetic resonance imaging agent. After formation of an oleic acid-gelatin shell, the prepared materials exhibited high loading capacity for a hydrophobic anticancer drug (paclitaxel). Our particle platform system exhibited higher therapeutic efficacy and lower toxicological effects in vitro and in an in vivo cancer model than a clinically available chemo-drug (Taxol®). Our findings strongly suggest that this nanoparticle system can serve as a platform for cancer therapy by the incorporation of chemical drugs. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate a fixed dose combination (FDC) of telmisartan (TEL) and pravastatin sodium (PRA) in enteric-coated bilayer tablets, which was designed for once-daily bedtime dose in order to match circadian rhythmic variations of hypertension and cholesterol synthesis and optimize the patient friendly dosing treatment. Due to the poor aqueous solubility of TEL, ternary solid dispersions (SD) consisting of TEL, polyethylene glycol 6000 (PEG 6000) and magnesium oxide (MgO) were designed to enhance its dissolution rate in intestinal fluid. MgO was added as an effective alkalizer to maintain the high microenvironmental pH of the saturated solution in the immediate vicinity of TEL particles because TEL is known to be ionizable but poorly soluble in intestinal fluid. In contrast, PRA is known to be very unstable in low pH conditions. In the SD system, TEL was present in an amorphous structure and formed an intermolecular hydrogen bonding with MgO, giving complete drug release without precipitation in intestinal fluid. In addition, the amount of hydrophilic carrier (PEG 6000) was also a factor. In the design of tablet formulation, the diluents and superdisintegrants could play a key role in release profiles. Then, to fulfill the unmet needs of the two model drugs and match circadian rhythmic variations of hypertension and cholesterol synthesis, enteric-coated bilayer tablet consisting of TEL SD and PRA was finally prepared using Acryl-EZE ® as an enteric coating material. Prior to enteric coating, a seal coating layer (Opadry ® , 2% weight gains) was firstly introduced to separate the core bilayer tablet from the acidic enteric coating polymers to avoid premature degradation. Dissolution profiles of finished tablets revealed that enteric-coated bilayer tablets with 6% weight gains remained intact in acidic media (pH 1.0) for 2 h and then released drugs completely within 45 min after switching to the intestinal media (pH 6.8). It was observed that enteric-coated bilayer tablets were stable during 3 month under the accelerated condition of 40 °C/75% RH. The delayed drug release and bedtime dosage regimen using enteric-coated bilayer tablet containing TEL and PRA, matching the circadian rhythms of hypertension and hyperlipidemia can provide therapeutic benefits for elderly patients in terms of maximizing the therapeutic effects. [ABSTRACT FROM AUTHOR]

Abstract: The present study was aimed to investigate the effect of food components and dosing time on the oral exposure of nifedipine in rats. Nifedipine was given orally to rats with and without food components at 8:00a.m. (morning time) or 4:00p.m. (evening time) during winter periods. Food components included milk, sodium chloride, oleic acid, and sodium taurocholate. Plasma concentration profiles of nifedipine showed double peak phenomena which were generally retained regardless of food components, vehicle types and the dosing time. Sodium chloride, milk and sodium taurocholate significantly increased the AUC while oleic acid did not, when drug was dosed in the morning time. After the dosing in the evening time, milk and sodium chloride significantly increased the plasma concentrations of nifedipine but oleic acid and sodium taurocholate decreased them. Overall, the systemic in vivo exposure of nifedipine was invariably lower with the evening dosing compared to the dosing in the morning, but this circadian rhythm dependency was not reversed by the multiple dosing of food components in rats. Food components and dosing time significantly altered the oral pharmacokinetics of nifedipine in rats, implying that the altered bioavailability and higher plasma concentrations in the morning time may influence dosing regimens of nifedipine for hypertension patients. [Copyright &y& Elsevier]

The long history of discovery and recently encouraging studies of the anti-cancer effect of aspirin promise a closer step to widely used aspirin-based medication in cancer therapy. To resolve the poor water-solubility of aspirin and low encapsulation efficiency of exosomes for further developing a new delivery of aspirin as anti-cancer treatment, our nanoamorphous exosomal delivery platform was established. In this study, the anti-tumour effects of nanoamorphous aspirin-loaded exosomes with exosomes derived from breast and colorectal cancer cells, were comprehensively studied using both in vitro and in vivo models. These exosomes displayed enhanced cellular uptake via both clathrin-dependent and -independent endocytosis pathways, and significantly improved cytotoxicity of aspirin to breast and colorectal cancer cells, accompanied by the enhanced apoptosis and autophagy. Remarkably, this nanoamorphous exosomal platform endowed aspirin with the unprecedented cancer stem cell eradication capacity. Further animal study demonstrated that this developed exosomal system was able to efficiently deliver aspirin to in vivo tumours. The active targeting of these exosomes to tumour was further improved by conjugating an aptamer specifically targeting EpCAM protein. Hence, this nanoamorphous structured exosome system effectively transformed aspirin into a potential cancer stem cell killer with distinguished properties for clinical translation. [ABSTRACT FROM AUTHOR]