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Κυριακή 4 Μαρτίου 2018

Phytotoxicity and cytogenotoxicity of hydroalcoholic extracts from Solanum muricatum Ait. and Solanum betaceum Cav. (Solanaceae) in the plant model Lactuca sativa

Abstract

Plants are rich in biologically active compounds. They can be explored for the production of bioherbicides. In this context, the present work aimed to evaluate the allelopathic effect of hydroalcoholic extracts from two Solanaceae species: Solanum muricatum Ait. and Solanum betaceum Cav. For this end, we conducted phytochemical screening and biological assays, determining the effects of the extracts on germination, early development, cell cycle, and DNA fragmentation in plantlets and meristematic cells of the plant model Lactuca sativa L. (lettuce). The percentage of seeds germinated under effect of S. muricatum extract did not differ from the control, but plantlet growth was reduced at the highest concentrations. For S. betaceum extract, dose dependence was observed for both germination and plantlet development, with the highest concentrations inhibiting germination. The growth curves revealed the concentrations of 2.06 and 1.93 g/L for S. muricatum and S. betaceum extracts, respectively, as those reducing 50% of root growth (RG). At these concentrations, both extracts presented mitodepressive effect, besides inducing significant increase in the frequency of condensed nuclei, associated to DNA fragmentation and cytoplasmic shrinkage. The frequency of chromosome alterations was not significant. We further discuss the mechanisms of action related to the chemical composition of the extracts, which presented organic acids, reducing sugars, proteins, amino acids, and tannins, besides catechins and flavonoids, only found in the extract of S. betaceum.



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Correction to: Risk exposure assessment of per- and polyfluoroalkyl substances (PFASs) in drinking water and atmosphere in central eastern China

Abstract

The original publication of this paper contains a mistake.



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Anti-Helicobacter pylori therapy in localized gastric mucosa-associated lymphoid tissue lymphoma: A prospective, nationwide, multicenter study in Japan

Abstract

Background

Helicobacter pylori eradication therapy was approved in Japan for the first-line, standard treatment of H. pylori-positive gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Although several retrospective studies or small-scale single-center studies have been reported, a prospective, large-scale, nationwide, multicenter study has not been reported from Japan.

Materials and Methods

We conducted a prospective, nationwide, multicenter study to evaluate the clinical efficacy of rabeprazole-based triple H. pylori eradication therapy for patients with localized gastric MALT lymphoma in practice-based clinical trial. A total of 108 H. pylori-positive patients with stage I/II1 gastric MALT lymphoma underwent H. pylori eradication therapy. The primary endpoints were complete remission (CR) rate and the rate of transfer to secondary treatment. The secondary endpoints were CR maintenance duration and overall survival (OS).

Results

CR of lymphoma was achieved in 84 of 97 patients (86.6%), during the period 2.0-44.7 months (median, 5.3 months) after starting H. pylori eradication treatment. CR was maintained in 77 of 81 patients (95.1%) for 0.4-53.2 months (median, 33.1 months). Secondary treatments (radiotherapy, rituximab, or gastrectomy) for gastric MALT lymphoma were needed in 10 of the 97 patients (10.31%). During follow-up, OS rate was 96.9% (94/97) and the causes of 3 deaths were not related to lymphoma.

Conclusions

Rabeprazole-based H. pylori eradication therapy demonstrated a high CR rate, long CR maintenance, and a good OS for patients with localized gastric MALT lymphoma in this prospective, practice-based, multicenter study.



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Brief report: Lactobacillus bulgaricus GLB44 (Proviotic™) plus esomeprazole for Helicobacter pylori eradication: A pilot study

Abstract

Background

Recent studies of Lactobacillus delbrueckii subsp. bulgaricus GLB44 plus a proton-pump inhibitor (PPI) reported cures of more than 90% of patients with active Helicobacter pylori infections.

Aim

To confirm the high H. pylori cure rates reported previously.

Method

A pilot study was done in healthy H. pylori-infected volunteers using 3-gram sachet (3 billion cells) of L. delbrueckii GLB44 plus 22.3 mg of esomeprazole b.i.d., for 14 days. The result was determined by urea breath testing 4 weeks after therapy. Stopping rules required for ending enrollment if less than 3 of the first 10 subjects were cured.

Results

Nine subjects were entered and because all failed to achieve negative urea breath test, the stopping rule required the study to end.

Conclusion

We were unable to confirm reports of achieving a high H. pylori cure rate with L. delbrueckii GLB44 plus a PPI.



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The effect of mesenchymal stem cells combined with platelet-rich plasma on skin wound healing

Summary

Introduction

Mesenchymal stem cells (MSCs) are multipotent stem cells that have the potential of proliferation, high self-renewal, and the potential of multilineage differentiation. The differentiation potential of the MSCs in vivo and in vitro has caused these cells to be regarded as potentially appropriate tools for wound healing. After the burn, trauma or removal of the tumor of wide wounds is developed. Although standard treatment for skin wounds is primary healing or skin grafting, they are not always practical mainly because of limited autologous skin grafting.

Evidence Acquisitions

Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO), and Web of Science have been searched.

Evidence Synthesis

For clinical use of the MSCs in wound healing, two key issues should be taken into account: First, engineering biocompatible scaffolds clinical use of which leads to the least amount of side effects without any immunologic response and secondly, use of stem cells secretions with the least amount of clinical complications despite their high capability of healing damage.

Conclusion

In light of the MSCs' high capability of proliferation and multilineage differentiation as well as their significant role in modulating immunity, these cells can be used in combination with tissue engineering techniques. Moreover, the MSCs' secretions can be used in cell therapy to heal many types of wounds. The combination of MSCs and PRP aids wound healing which could potentially be used to promote wound healing.



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Cytokine profile (IL-2, IL-6, IL-17, IL-22, and TNF-α) in vitiligo—New insight into pathogenesis of disease

Summary

Background

Vitiligo is an autoimmune disease associated with alteration in levels of various cytokines. However, there are very few studies in this regard.

Objectives

To assess the serum levels of cytokines secreted by Th1 (IL-2, TNF-α), Th2 (IL-6), and Th17 cells (IL-17, IL-22) in patients with localized vitiligo and generalized vitiligo and to correlate their levels with the extent, duration, and activity of disease.

Material and Methods

Sixty patients of vitiligo (30 each of localized and generalized) and 30 controls were recruited in the study. Serum IL-2, -6, -17, -22, and TNF-α levels were measured by enzyme-linked immunosorbent assay (ELISA) in all patients and healthy controls, and their levels were correlated with the extent, duration, and activity of vitiligo.

Results

We observed significantly raised levels of IL-2, -6, -17, -22, and TNF-α in both localized vitiligo and generalized vitiligo (P < .05). IL-2 was significantly raised (P = .028) in localized vitiligo, whereas IL-17 and IL-22 were significantly raised in generalized vitiligo (P = .00 and P = .019, respectively). Activity of disease showed positive correlation with serum TNF-α levels (P = .015) in localized vitiligo. Positive correlation of IL-17 (R = .238) with body surface area (BSA) was observed in patients with generalized vitiligo.

Conclusions

Our study shows that cytokines secreted by Th17 cells play an important role in maintenance and spread of vitiligo as they increase in line with extent of disease. Also TNF-α increases in proportion with activity of disease, hence may act as biomarker for identifying patient with aggressive disease.



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Effect of hyperbaric oxygen on the process of hypertrophic scar formation in rabbit ears

Summary

Objective

To explore the influence of hyperbaric oxygen on scar formation in rabbit ears.

Methods

A total of 20 New Zealand rabbits were selected to establish the hypertrophic scar model on the ears. The rabbits were randomly divided into control group and experimental group (7d, 14d, 21d, and 28d group according to different HBO treatment days),each experimental group received hyperbaric oxygen treatment after the operation at the same time everyday for 1 hour. After the day 29, the scars were collected. Histomorphological change in scars was observed by hematoxylin-eosin staining, Masson staining, and transmission electrical microscope. The expression of bax, bcl-2, and the cell apoptosis rate was detected by immunohistochemical method.

Results

(i) Both number of fibroblast and amount of collagen fibrils in experimental group were significantly reduced compared with those in control group. In Masson staining, arrangement of collagen fibrils in experimental group was much more irregular and coarse than control groups. (ii) HI value can be found much smaller in the experimental groups than the control (P < .05). Among the four experimental groups, there is significant difference among 7d, 14d, and 21d groups (P < .05), while there is no difference between 21d and 28d groups (P > .05). (iii) Expression of Bax could be detected up-regulated in experimental group (P < .05). While the expression of Bcl-2 is detected significantly down-regulated in experimental group than that in control group (P < .05). Compared with the 7d group, the expression of Bax and Bcl-2 has significant difference in 14d group (P < .05), and the expression of this two factors in 21d group has significant difference comparing with 14d group(P < .05),but there is no significant difference between 28d group and 21d group(P > .05). (iv) Significant difference of cell apoptosis rate can be detected between the experimental groups and the control group (P < .05). Among the four experimental groups, there is significant difference among 7d, 14d, and 21d groups (P < .05), while there is no difference between 21d and 28d groups (P > .05).

Conclusion

The hyperbaric oxygen can up-regulate bax/bcl-2 value, increase the cell apoptosis rate, and inhibit the early hypertrophic scar in rabbit ears.



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A single-center clinical trial to evaluate the efficacy of a tripeptide/hexapeptide antiaging regimen

Summary

Introduction

An antiaging regimen that aids in clearing the matrix of waste products and stimulating neocollagenesis and neoelastogenesis was tested among a group of subjects over the course of 12 weeks to assess its efficacy in women with mild to moderate wrinkles and skin sagging on the face.

Materials and methods

The efficacy of the product regimen was tested in 22 subjects using investigator clinical grading measurements, raking light imaging, 3D imaging, biopsies, and self-assessment questionnaires at baseline and weeks 4, 8, and 12.

Results

Clinical grading indicated that use of the antiaging regimen for 12 weeks produced a statistically significant improvement in scores for all evaluated parameters; the raking light image analysis demonstrated a statistically significant improvement in values for length, width, and area of wrinkles when compared with baseline values as did 3D imaging. Biopsy results in the 5 patients tested showed improvement in solar elastosis, collagen stimulation, and improvement in cornified layers in all 5 patients. Elastin stimulation was evident in 3 of 5 patients. Results from the self-assessment questionnaire analysis indicated favorable responses in a statistically significant proportion of subjects after 12 weeks of use for all inquiries.

Conclusion

Use of this facial antiaging regimen was effective in improving visual facial photoaging conditions and well-perceived when used by women with mild to moderate wrinkles and skin sagging on the face under the conditions of this study.



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A gendered strength-based treatment model for female sexual offenders

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Publication date: Available online 4 March 2018
Source:Aggression and Violent Behavior
Author(s): Dawn M. Pflugradt, Bradley P. Allen, William L. Marshall
Due to the relatively limited knowledge about female sexual offenders, treatment approaches and programs have been primarily based upon models developed for male perpetrators. Although male and female offenders share some common characteristics, there is increasing empirical evidence that many aspects of female sexual offending behaviors are separate and different from those of males. By integrating theoretical constructs from the current literature, this paper proposes a strength-based treatment approach utilizing a gendered paradigm of female sexual offending. In general, a gendered strength-based treatment model involves a collaborative process that builds upon positive skills and provides options to utilize those skills to fulfill unmet needs. This treatment process also considers the contextual nature of the female sexual offender's social functioning and the individual manifestations of her sexually assaultive behaviors.



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Virtual reality rehabilitation with functional electrical stimulation improves upper extremity function in patients with chronic stroke: a pilot randomized controlled study

Publication date: Available online 2 March 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Stephanie Hyeyoung Lee, Ji-Yeong Lee, Mi-Young Kim, Yu-Jin Jeon, Suyoung Kim, Joon-Ho Shin
ObjectiveTo compare virtual reality (VR) combined with functional electrical stimulation (FES) to cyclic FES for improving upper extremity function and health-related quality of life in patients with a chronic stroke.DesignA pilot, randomized, single blinded, controlled trial.SettingStroke rehabilitation inpatient unitParticipantsForty-eight participants with a hemiplegia secondary to a unilateral stroke for >3 months, with a hemiplegic wrist extensor Medical Research Council (MRC) scale score of 1–3.InterventionsFES was applied to the wrist extensors and finger extensors. A virtual-reality(VR) based wearable rehabilitation device was used, combined with FES and virtual activity-based training. The control group received cyclic FES only. Both groups completed 20 sessions, over a 4-week period.Main outcome measuresPrimary outcomes were the change in the Fugl–Meyer Assessment: upper extremity (FMA) and Wolf Motor Function Test (WMFT) scores. Secondary outcomes were the change in the Box and Block test (BB), Jebsen Taylor Hand Function Test (JTT), and Stroke Impact Scale (SIS) scores. Assessments were performed at baseline (T0) and at 2 weeks (T1), 4 weeks (T4), and 8 weeks (T8). Between-group comparisons were evaluated using a repeated measures analysis of variance.ResultsForty-one participants were included in the analysis. Compared to FES alone, VR-FES produced greater increase in FMA–distal score (p=0.011) and marginal improvement in JTT–gross score (p=0.057). VR-FES produced greater, although non-significant, improvements in all other outcome measures, except in the SIS–ADL/IADL score.ConclusionsFES with VR-based rehabilitation may be more effective than cyclic FES to improve distal gross upper extremity function post-stroke.



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Gait Training in Acute Spinal Cord Injury Rehabilitation – Utilization and Outcomes Among Non-Ambulatory Individuals: Findings from the SCIRehab Project

Publication date: Available online 3 March 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Stephanie Rigot, Lynn Worobey, Michael L. Boninger
ObjectivesTo investigate relation of gait training (GT) during inpatient rehabilitation (IPR) to outcomes of people with traumatic spinal cord injury (SCI).DesignProspective observational study using the SCIRehab database.SettingSix IPR facilities.ParticipantsPatients with new SCI receiving initial rehabilitation (n=1376).InterventionsPatients were divided into groups of who did and did not receive GT. Patients were further subdivided based on their primary mode of mobility as measured by the Functional Independence Measure (FIM).Outcome MeasuresPain rating scales; Patient Health Questionnaire Mood Subscale; Satisfaction with Life Scale (SWLS); and Craig Handicap Assessment and Reporting Technique (CHART).ResultsNearly 58% of all patients received GT, including 33.3% of patients who were primarily using a wheelchair 1-year after discharge from IPR. Those who used a wheelchair and received GT, received significantly less transfer and wheeled mobility training (p<.001). CHART physical independence (p=.002), mobility (p=.024), and occupation (p=.003) scores were significantly worse in patients who used a wheelchair at 1-year and received GT, compared to those who used a wheelchair and did not receive GT in IPR. Older age was also a significant predictor of worse participation as measured by the CHART.ConclusionsA significant percentage of individuals who are not likely to become functional ambulators are spending portions of their IPR stays performing GT, which is associated with less time allotted for other functional interventions. GT in IPR was also associated with participation deficits at 1-year for those who used a wheelchair, implying the potential consequences of opportunity costs, pain, and psychological difficulties of receiving unsuccessful GT. Clinicians should consider this data when deciding to implement gait training during initial inpatient rehabilitation.



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Low-level clonal FGFR2 amplification defines a unique molecular subtype of intrahepatic cholangiocarcinoma in a Chinese population

Publication date: Available online 4 March 2018
Source:Human Pathology
Author(s): Xiao-Hong Pu, Qing Ye, Jun Yang, Hong-Yan Wu, Xi-Wei Ding, Jiong Shi, Liang Mao, Xiang-Shan Fan, Jun Chen, Yu-Dong Qiu, Qin Huang
Intrahepatic cholangiocarcinoma (ICC) is a subtype of primary liver cancer rarely curable by surgery that is increasing rapidly in incidence. Chromosomal translocations and amplifications of the fibroblast growth factor receptor 2 (FGFR2) locus are present in several kinds of tumors including ICC, but their incidence has not been assessed in Chinese patients. Using break-apart probes and by determining the ratios of FGFR2/chromosome enumeration probe (CEP) 10 double-color probes, we evaluated 122 ICCs for the presence of FGFR2 translocations and amplifications, respectively, by fluorescence in situ hybridization (FISH). We further determined FGFR2 protein expression by immunohistochemistry and analyzed the clinicopathologic records of the patients. Eight tumors (6.6%) had FGFR2 translocations, whereas 15 (12.3%) had low-level FGFR2 amplification. Interestingly, the tumors that showed both translocation and low-level amplification frequently were of the mass-forming (MF) type. Compared with the ICCs with normal FGFR2s, tumors with amplifications secreted less mucus (P = .017) and typically were accompanied by hepatitis B virus infection (P = .004). Tumors with low-level amplification generally were of lower stage (P = .013) and associated with better overall survival (P = .017). As tumors with FGFR2 amplification exhibit different biology from lesions with a normal gene, low-level amplification of FGFR2 may play an important role in tumor progression and may be a marker for targeted therapy.



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Phosphaturic Mesenchymal Tumor Without Osteomalacia: Additional Confirmation of the “Non-Phosphaturic” Variant, with Emphasis on the Roles of FGF23 Chromogenic in situ Hybridization and FN1-FGFR1 Fluorescence in situ Hybridization

Publication date: Available online 4 March 2018
Source:Human Pathology
Author(s): Kimberley N Sent-Doux, Craig Mackinnon, Jen-Chieh Lee, Andrew L Folpe, Omar Habeeb
Phosphaturic Mesenchymal Tumor (PMT) is a rare, histologically distinctive neoplasm, which classically presents with phosphaturia and tumor-induced osteomalacia (TIO) (i.e., oncogenic osteomalacia). Both the phosphaturia and TIO are due to paraneoplastic production of FGF23 (a phosphatonin) by the neoplastic cells, which are genetically characterized by rearrangements of FN1 (most often with FGFR1 – and less frequently with FGF1). However, rare cases of PMT present without phosphaturia and TIO (i.e., the "non-phosphaturic" variant) – and are therefore much more challenging to diagnose. Here, we report the first case of a genetically confirmed, non-phosphaturic PMT – in which the correct diagnosis was established through a combination of careful histological evaluation, FGF23 chromogenic in situ hybridization (CISH), and fluorescence in situ hybridization (FISH) testing for FN1-FGFR1.



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Propranolol prevents liver cirrhosis by inhibiting hepatic stellate cell activation mediated by the PDGFR/Akt pathway

Publication date: Available online 4 March 2018
Source:Human Pathology
Author(s): Qian Ding, Zhen Li, Bin Liu, Liping Ling, Xiangguo Tian, Chunqing Zhang
Propranolol is known to reduce portal pressure by decreasing blood flow to the splanchnic circulation and the liver. However, it is unknown if propranolol improves fibrogenesis and sinusoidal remodeling in the cirrhotic liver. The aim of this study was to investigate the therapeutic effects of propranolol on carbon tetrachloride (CCl4)-induced liver fibrosis in a mouse model and the intrinsic mechanisms underlying those effects. In this study, a hepatic cirrhosis mouse model was induced by CCl4 administration for 6weeks. Propranolol was simultaneously administered orally in the experimental group. Liver tissue and blood samples were collected for histological and molecular analyses. LX-2 cells induced by platelet-derived growth factor-BB (PDGF-BB) were used to evaluate the anti-fibrogenic effect of propranolol in vitro. The results showed that treatment of mice with CCl4 induced hepatic fibrosis, as evidenced by inflammatory cell infiltration, collagen deposition and abnormal vascular formation in the liver tissue. All these changes were significantly attenuated by propranolol treatment. Furthermore, we also found that propranolol inhibited PDGF-BB-induced hepatic stellate cell migration, fibrogenesis, and PDGFR/Akt phosphorylation. Taken together, propranolol might prevent CCl4-induced liver injury and fibrosis at least partially through inhibiting the PDGF-BB-induced PDGFR/Akt pathway. The anti-fibrogenic effect of propranolol may support its status as a first-line treatment in patients with chronic liver disease.



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Classic biphasic pulmonary blastoma: a case report and review of the literature

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Publication date: Available online 3 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Hervé Le Caer




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Evaluation of Fixed-Dose Four-Factor Prothrombin Complex Concentrate for Emergent Warfarin Reversal in Patients with Intracranial Hemorrhage

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Publication date: Available online 3 March 2018
Source:The Journal of Emergency Medicine
Author(s): Rachael Scott, Brian Kersten, Jeanne Basior, Megan Nadler
BackgroundDifferent strategies exist for dosing four-factor prothrombin complex concentrate (PCC4) for international normalized ratio (INR) reversal in the setting of life-threatening bleeding. Fixed doses ranging from 1000 IU to 1750 IU have demonstrated efficacy similar to weight-based dosing, however, few studies look exclusively at intracranial hemorrhage (ICH).ObjectiveOur aim was to evaluate whether a fixed dose of 1000 IU of PCC4 achieves INR reversal similar to weight-based dosing in patients with ICH who were anticoagulated with warfarin.MethodsWe compared a weight-based dose vs. 1000 IU PCC4 between January 2014 and January 2017. The primary end point was achieving an INR < 1.5. Secondary end points included in-hospital mortality, patient disposition, and reversal defined by INR < 1.6.ResultsA total of 31 patients were included in the weight-based group and 30 were included in the fixed-dose group, with baseline INRs of 2.98 and 2.84, respectively (p = 0.39). Twenty-two patients (71%) achieved an INR < 1.5 in the weight-based group vs. 16 (53%) in the fixed-dose group (p = 0.15), while 25 (81%) achieved an INR < 1.6 in the weight-based group vs. 22 (73%) in the fixed-dose group (p = 0.49). There was no difference in the number of patients discharged to home (19% vs. 20%; p = 0.95) or in-hospital mortality (26% vs. 27%; p = 0.93).ConclusionsWe found a non−statistically significant difference in warfarin reversal to an INR goal of < 1.5 when comparing a fixed dose of 1000 IU PCC4 and a weight-based dose for ICH. Further studies correlating clinical outcomes with INR reversal are needed.



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Improvement of a mixture experiment model relating the component proportions to the size of nanonized itraconazole particles in extemporary suspensions

Publication date: Available online 3 March 2018
Source:European Journal of Pharmaceutical Sciences
Author(s): Franco Pattarino, Greg Piepel, Maurizio Rinaldi
A paper by Foglio Bonda et al. published previously in this journal (2016, Vol. 83, pp. 175–183) discussed the use of mixture experiment design and modeling methods to study how the proportions of three components in an extemporaneous oral suspension affected the mean diameter of drug particles (Zave). The three components were itraconazole (ITZ), Tween 20 (TW20), and Methocel® E5 (E5). This commentary addresses some errors and other issues in the previous paper, and also discusses an improved model relating proportions of ITZ, TW20, and E5 to Zave. The improved model contains six of the 10 terms in the full-cubic mixture model, which were selected using a different cross-validation procedure than used in the previous paper. Compared to the four-term model presented in the previous paper, the improved model fit the data better, had excellent cross-validation performance, and the predicted Zave of a validation point was within model uncertainty of the measured value.

Graphical abstract

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The role of lactose carrier on the powder behavior and aerodynamic performance of bosentan microparticles for dry powder inhalation

Publication date: Available online 3 March 2018
Source:European Journal of Pharmaceutical Sciences
Author(s): Hyo-Jung Lee, Hong-Goo Lee, Yong-Bin Kwon, Ju-Young Kim, Yun-Seok Rhee, Jinmann Chon, Eun-Soek Park, Dong-Wook Kim, Chun-Woong Park
In this study, we prepared carrier-based formulations for dry powder inhalers by mixing bosentan microparticles with carrier, prepared in three separate types of lactose. Spray-dried, milled and sieved lactose resulted in formulations with various shapes, surface morphology and particle size distributions. In the spray-dried lactose, the micronized bosentan particles were trapped and strongly interlocked in the rugged surface of spray-dried lactose, whereas in the milled and sieved lactose they exhibited lower binding affinity onto the smooth surface of carrier. In all of the carrier-based formulations, the flow properties were improved compared with bosentan microparticles alone, in the following order spray-dried, sieved and milled lactose. The aerodynamic characteristics of each were evaluated by particle image velocimetry and Andersen cascade impactor™. Depending on the lactose carrier type, particle dispersion showed different flow characteristics. In the spray-dried lactose, the formulation was dispersed fast in the only frontal direction, while the milled and sieved lactose formulations formed a relatively slower S-shaped and fountain-shaped flow stream, respectively. In addition, milled and sieved lactose formulations showed that the drug particles were readily liberated from the lactose carrier, and demonstrated significantly higher aerosol performance than spray-dried lactose.

Graphical abstract

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