scholarly journals Balance of Drug Residence and Diffusion in Lacrimal Fluid Determine Ocular Bioavailability in In Situ Gels Incorporating Tranilast Nanoparticles

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1425
Author(s):  
Misa Minami ◽  
Hiroko Otake ◽  
Yosuke Nakazawa ◽  
Norio Okamoto ◽  
Naoki Yamamoto ◽  
...  
Keyword(s):  
Residence Time ◽  
Pluronic F127 ◽  
Lacrimal Fluid ◽  
Significant Difference ◽  
Bead Mill ◽  
Conjunctival Inflammation ◽  
Ocular Bioavailability ◽  
Factor Α ◽  
And Diffusion

We previously designed ophthalmic formulations (nTRA) containing tranilast nanoparticles (Tra-NPs) with high uptake into ocular tissues. In this study, we used in situ gel (ISG) bases comprising combinations of pluronic F127 (F127) and methylcellulose (MC/F127), pluronic F68 (F68/F127), and Carbopol (Car/F127), and we developed in situ gels incorporating Tra-NPs (Tra-NP-incorporated ISNGs) such as nTRA-F127, nTRA-MC/F127, nTRA-F68/F127, and nTRA-Car/F127. Moreover, we demonstrated the therapeutic effect on conjunctival inflammation using lipopolysaccharide-induced rats. Each Tra-NP-incorporated ISNG was prepared by the bead mill method, the particle size was 40–190 nm, and the tranilast release and diffusion from formulation were nTRA > nTRA-F127 > nTRA-F68/F127 > nTRA-Car/F127 > nTRA-MC/F127. In the Tra-NP-incorporated ISNGs, the tranilast residence time in the lacrimal fluid, cornea, and conjunctiva was prolonged, although the Cmax was attenuated in comparison with nTRA. On the other hand, no significant difference in conjunctival inflammation between non- and nTRA-F127-instilled rats was found; however, the nTRA-F68/F127, nTRA-Car/F127, and nTRA-MC/F127 (combination-ISG) attenuated the vessel leakage, nitric oxide, and tumor necrosis factor-α expression. In particular, nTRA-F68/F127 was significant in preventing the conjunctival inflammation. In conclusion, we found that the combination-ISG base prolonged the residence time of Tra-NPs; however, Tra-NP release from the formulation was attenuated, and the Tmax was delayed longer than that in nTRA. The balance of drug residence and diffusion in lacrimal fluid may be important in providing high ocular bioavailability in formulations containing solid nanoparticles.

scholarly journals In Situ Gelling Systems Using Pluronic F127 Enhance Corneal Permeability of Indomethacin Nanocrystals

2020 ◽  
Vol 21 (19) ◽  
pp. 7083
Author(s):  
Noriaki Nagai ◽  
Takumi Isaka ◽  
Saori Deguchi ◽  
Misa Minami ◽  
Mizuki Yamaguchi ◽  
...  
Keyword(s):  
Pluronic F127 ◽  
Significant Information ◽  
Corneal Permeability ◽  
Enhanced Absorption ◽  
Bead Mill ◽  
Resident Time ◽  
Energy Dependent ◽  
Corneal Permeation ◽  
In Situ Gelling

We previously designed an ophthalmic dispersion containing indomethacin nanocrystals (IMC-NCs), showing that multiple energy-dependent endocytoses led to the enhanced absorption of drugs from ocular dosage forms. In this study, we attempted to prepare Pluronic F-127 (PLF-127)-based in situ gel (ISG) incorporating IMC-NCs, and we investigated whether the instillation of the newly developed ISG incorporating IMC-NCs prolonged the precorneal resident time of the drug and improved ocular bioavailability. The IMC-NC-incorporating ISG was prepared using the bead-mill method and PLF-127, which yielded a mean particle size of 50–150 nm. The viscosity of the IMC-NC-incorporating ISG was higher at 37 °C than at 10 °C, and the diffusion and release of IMC-NCs in the IMC-NC-incorporating ISG were decreased by PLF-127 at 37 °C. In experiments using rabbits, the retention time of IMC levels in the lacrimal fluid was enhanced with PLF-127 in the IMC-NC-incorporating ISG, whereby the IMC-NC-incorporating ISG with 5% and 10% PLF-127 increased the transcorneal penetration of the IMCs. In contrast to the results with optimal PLF-127 (5% and 10%), excessive PLF-127 (15%) decreased the uptake of IMC-NCs after instillation. In conclusion, we found that IMC-NC-incorporating ISG with an optimal amount of PLF-127 (5–10%) resulted in higher IMC corneal permeation after instillation than that with excessive PLF-127, probably because of the balance between higher residence time and faster diffusion of IMC-NCs on the ocular surface. These findings provide significant information for developing ophthalmic nanomedicines.

Increse of newly - detected in situ cancers in non-palpable breast lesions

2006 ◽  
Vol 53 (1) ◽  
pp. 73-75
Author(s):  
N. Miletic ◽  
D. Stojiljkovic ◽  
M. Inic ◽  
M. Prekajski ◽  
A. Celebic ◽  
...  
Keyword(s):  
Breast Tissue ◽  
Malignant Disease ◽  
Clinical Stage ◽  
Diagnostic Procedures ◽  
Basal Membrane ◽  
Needle Aspiration ◽  
Screening Mammography ◽  
Significant Difference ◽  
Malignant Lesions

Great importance in detecting cancer in the phase of in situ lays in the fact that the epithelial layer is deprived of blood and lymph vessels, so metastases may develop only when basal membrane has been broken. This paper includes 46 operated women in whom it preoperatively had been verified suspect non-palpable lesion. The preoperative diagnostics included use of high- resolution mammography, aimed mammography, palpatory examination, as well as fine-needle aspiration (FNA), biopsy and cytologic analysis of the sample. The methodology of this work implies the use of stereotaxic marking, specimen mammography and ex-tempore pathohistology analysis. Out of 46 investigated patients in clinical stage T0N0M0, in whom there were no signs of malignant disease, and according to suspect lesion of initial screening mammography, malignant lesions of breast tissue were diagnosed in 19 patients (41%) intraoperatively. Three of these lesions (15,8%) were histopathologically verified as in situ. Comparing our results with data of the Institute of oncology and radiology of Serbia hospital registry (IORS) for the year 2001, from 1173 patients registered with malignant lesions, only 16 ones (1,4%) had in situ cancer, operated on the basis of the suspect mammography of clinical stage T0N0M0. Statistically significant difference was found related to the number of detected cancers in this early phase of the breast malignant disease. This limits surgical intervention to tumorectomy, with preservation of the remaining breast tissue, what brings to healing, justifying in that way, screening examinations and routine application of the most contemporary diagnostic procedures.

scholarly journals SMILE and Wavefront-Guided LASIK Out-Compete Other Refractive Surgeries in Ameliorating the Induction of High-Order Aberrations in Anterior Corneal Surface

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Min-jie Ye ◽  
Cai-yuan Liu ◽  
Rong-feng Liao ◽  
Zheng-yu Gu ◽  
Bing-ying Zhao ◽  
...  
Keyword(s):  
Spherical Aberration ◽  
Laser In Situ Keratomileusis ◽  
Small Incision Lenticule Extraction ◽  
Corneal Surface ◽  
Small Incision ◽  
Significant Difference ◽  
Lenticule Extraction ◽  
A Prospective Study ◽  
High Order Aberrations

Purpose. To compare the change of anterior corneal higher-order aberrations (HOAs) after laser in situ keratomileusis (LASIK), wavefront-guided LASIK with iris registration (WF-LASIK), femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK), and small incision lenticule extraction (SMILE).Methods. In a prospective study, 82 eyes underwent LASIK, 119 eyes underwent WF-LASIK, 88 eyes underwent FS-LASIK, and 170 eyes underwent SMILE surgery. HOAs were measured with Pentacam device preoperatively and 6 months after surgery. The aberrations were described as Zernike polynomials, and analysis focused on total HOAs, spherical aberration (SA), horizontal coma, and vertical coma over 6 mm diameter central corneal zone.Results. Six months postoperatively, all procedures result in increase of anterior corneal total HOAs and SA. There were no significant differences in the induced HOAs between LASIK and FS-LASIK, while SMILE induced fewer total HOAs and SA compared with LASIK and FS-LASIK. Similarly, WF-LASIK also induced less total HOAs than LASIK and FS-LASIK, but only fewer SA than FS-LASIK (P<0.05). No significant difference could be detected in the induced total HOAs and SA between SMILE and WF-LASIK, whereas SMILE induced more horizontal coma and vertical coma compared with WF-LASIK (P<0.05).Conclusion. FS-LASIK and LASIK induced comparable anterior corneal HOAs. Compared to LASIK and FS-LASIK, both SMILE and WF-LASIK showed advantages in inducing less total HOAs. In addition, SMILE also possesses better ability to reduce the induction of SA in comparison with LASIK and FS-LASIK. However, SMILE induced more horizontal coma and vertical coma compared with WF-LASIK, indicating that the centration of SMILE procedure is probably less precise than WF-LASIK.

scholarly journals Effects of Fermented Milk Containing Lacticaseibacillus paracasei Strain Shirota on Constipation in Patients with Depression: A Randomized, Double-Blind, Placebo-Controlled Trial

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2238
Author(s):  
Xiaomei Zhang ◽  
Shanbin Chen ◽  
Ming Zhang ◽  
Fazheng Ren ◽  
Yimei Ren ◽  
...  
Keyword(s):  
Mental Illness ◽  
Placebo Group ◽  
Rating Scale ◽  
Controlled Trial ◽  
Fermented Milk ◽  
Daily Consumption ◽  
Double Blind ◽  
Tnf Α ◽  
Significant Difference ◽  
Factor Α

Probiotics have been shown to benefit patients with constipation and depression, but whether they specifically alleviate constipation in patients with depression remains unclear. The aim of this study was to investigate the effect of Lacticaseibacillus paracasei strain Shirota (LcS), formerly Lactobacillus casei strain Shirota, on constipation in patients with depression with specific etiology and gut microbiota and on depressive regimens. Eighty-two patients with constipation were recruited. The subjects consumed 100 mL of a LcS beverage (108 CFU/mL) or placebo every day for 9 weeks. After ingesting beverages for this period, we observed no significant differences in the total patient constipation-symptom (PAC-SYM) scores in the LcS group when compared with the placebo group. However, symptoms/scores in item 7 (rectal tearing or bleeding after a bowel movement) and items 8–12 (stool symptom subscale) were more alleviated in the LcS group than in the placebo group. The Beck Depression Index (BDI) and Hamilton Depression Rating Scale (HAMD) scores were all significantly decreased, and the degree of depression was significantly improved in both the placebo and LcS groups (p < 0.05), but there was no significant difference between the groups. The LcS intervention increased the beneficial Adlercreutzia, Megasphaera and Veillonella levels and decreased the bacterial levels related to mental illness, such as Rikenellaceae_RC9_gut_group, Sutterella and Oscillibacter. Additionally, the interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) levels were significantly decreased in both the placebo and LcS groups (p < 0.05). In particular, the IL-6 levels were significantly lower in the LcS group than the placebo group after the ingestion period (p < 0.05). In conclusion, the daily consumption of LcS for 9 weeks appeared to relieve constipation and improve the potentially depressive symptoms in patients with depression and significantly decrease the IL-6 levels. In addition, the LcS supplementation also appeared to regulate the intestinal microbiota related to mental illness.

Verification of In Situ Thresholds and Integrated Real-Ear Measurements

2010 ◽  
Vol 21 (10) ◽  
pp. 663-670 ◽  
Author(s):  
Jeffrey J. DiGiovanni ◽  
Ryan M. Pratt
Keyword(s):  
Measurement System ◽  
Hearing Aids ◽  
Hearing Aid ◽  
Normal Hearing ◽  
Analysis Tool ◽  
Ohio University ◽  
Positive Direction ◽  
Significant Difference ◽  
Threshold Measurement

Background: Accurate prescriptive gain results in a more accurate fit, lower return rate in hearing aids, and increased patient satisfaction. In situ threshold measurements can be used to determine required gain. The Widex Corporation uses an in situ threshold measurement strategy, called the Sensogram. Real-ear measurements determine if prescriptive gain targets have been achieved. Starkey Laboratories introduced an integrated real-ear measurement system in their hearing aids. Purpose: To determine whether the responses obtained using the Widex Sensogram were equivalent to those obtained using current clinical threshold measurement methods. To determine the accuracy of the Starkey IREMS™ (Integrated Real Ear Measurement System) in measuring RECD (real-ear to coupler difference) values compared to a dedicated real-ear measurement system. Research Design: A verification design was employed by comparing participant data measured from standard, benchmark equipment and procedures against new techniques offered by hearing-aid manufacturers. Study Sample: A total of 20 participants participated in this study. Ten participants with sensorineural hearing loss were recruited from the Ohio University Hearing, Speech, and Language Clinic participated in the first experiment. Ten participants with normal hearing were recruited from the student population at Ohio University participated in both experiments. The normal-hearing group had thresholds of 15 dB HL or better at the octave frequencies of 250–8000 Hz. The hearing-impaired group had thresholds of varying degrees and configurations with thresholds equal to or poorer than 25 dB HL three-frequency pure-tone average. Data Collection and Analysis: The order of measurement method for both experiments was counterbalanced. In Experiment 1, thresholds obtained via the Widex Sensogram were compared to thresholds obtained for each participant using a clinical audiometer and ER-3A insert ear phones. In Experiment 2, RECD values obtained via the Starkey IREMS were compared to RECD values obtained via the Audioscan Verifit™. A repeated-measures analysis of variance (ANOVA) was used for statistical analysis, and a Fisher's LSD (least significant difference) was used as a post hoc analysis tool. Results: A significant difference between Sensogram thresholds and conventional audiometric thresholds was found with the Sensogram method resulting in better threshold values at 0.5, 1.0, and 2.0 kHz for both groups. In Experiment 2, a significant difference between RECD values obtained by the Starkey IREMS and the Audioscan Verifit system was found with significant differences in RECD values found at 0.25, 0.5, 0.75, 1.5, 2.0, and 6.0 kHz. Conclusions: The Sensogram data differ significantly from traditional audiometry at several frequencies important for speech intelligibility. Real-ear measures are still required for verification of prescribed gain, however, calling into question any claims of shortened fitting time. The Starkey IREMS does perform real-ear measurements that vary significantly from benchmark equipment. These technologies represent a positive direction in prescribing accurate gain during hearing-aid fittings, but a stand-alone system is still the preferred method for real-ear measurements in hearing-aid fittings.

scholarly journals In situ acoustic analysis of two twentieth-century heritage carillons

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Scott Allan Orr
Keyword(s):  
Twentieth Century ◽  
Acoustic Analysis ◽  
Mechanical Action ◽  
Ex Situ ◽  
Physical Acoustics ◽  
Acoustic Characteristics ◽  
Dynamic Level ◽  
Significant Difference ◽  
And Function

AbstractCarillons are a diverse and global form of musical and civic heritage: musical instruments comprised of a series of 23 or more bells, typically hung in a tower-like structure, tuned chromatically and played from a touch-sensitive manual and pedal console using an elaborate mechanical action. Carillon bells have a distinct series of musical overtones which should be accurately tuned to one another and with other bells they sound alongside. Although these overtones have been previously studied ex situ, this study assesses the acoustic characteristics of two early-twentieth century carillons in Toronto, Canada as a combination of structure, bells, and mechanical action. Thus, the instrument and its context are considered holistically, more accurately reflecting the musical sensitivity of a carillonist. Spectral analysis of audio samples of each bell at different musical dynamic levels enabled the analysis of the acoustic qualities of the bells and the mechanical action of the instruments. The tuning of bells in the instruments varied; most importantly, there was a significant difference between the audial intensity of the bell tones produced by the instruments, demonstrating the importance of the mechanical action as part of the ‘carillon system’. This was represented with a resistive power-law model, that represents the sensitivity of intensity to carillonist musical dynamic level. A discussion of the implications for artistic and heritage practice follows. Understanding the in situ physical acoustics of the carillon as a holistic instrument in its context informs performers, arrangers, and composers of how they can best embrace the instrument’s unique qualities to improve artistic pursuits and support the appreciation of carillons as heritage instruments and function as civic voices.

Molecular Cytogenetic Classification of Down Syndrome and Screening of Somatic Aneuploidy in Mothers

2021 ◽  
pp. 1-9
Author(s):  
Sushil Kumar Jaiswal ◽  
Ashok Kumar ◽  
Amit Kumar Rai
Keyword(s):  
Down Syndrome ◽  
Peripheral Blood ◽  
Trisomy 21 ◽  
Health Management ◽  
Chromosome 21 ◽  
Robertsonian Translocations ◽  
Significant Difference ◽  
And Control

Down Syndrome (DS) caused by trisomy 21 results in various congenital and developmental complications in children. It is crucial to cytogenetically diagnose the DS cases early for their proper health management and to reduce the risk of further DS childbirths in mothers. In this study, we performed a cytogenetic analysis of 436 suspected DS cases using karyotyping and fluorescent in situ hybridization. We detected free trisomies (95.3%), robertsonian translocations (2.4%), isochromosomes (0.6%), and mosaics (1.2%). We observed a slightly higher incidence of DS childbirth in younger mothers compared to mothers with advanced age. We compared the somatic aneuploidy in peripheral blood of mothers having DS children (MDS) and control mothers (CM) to identify biomarkers for predicting the risk for DS childbirths. No significant difference was observed. After induced demethylation in peripheral blood cells, we did not observe a significant difference in the frequency of aneuploidy between MDS and CM. In conclusion, free trisomy 21 is the most common type of chromosomal abnormality in DS. A small number of DS cases have translocations and mosaicism of chromosome 21. Additionally, somatic aneuploidy in the peripheral blood from the mother is not an effective marker to predict DS childbirths.

A quality of life assessment of military recruits after refractive surgery

2020 ◽  
Vol 1 (1) ◽  
pp. 42-46
Author(s):  
Jian-He Xiao ◽  
◽  
Shi-Yang Li ◽  
Xing Xing ◽  
Ai-Hong Zhao ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Refractive Error ◽  
High Myopia ◽  
Refractive Surgery ◽  
Laser In Situ Keratomileusis ◽  
Significant Difference ◽  
Lenticule Extraction ◽  
Postoperative Interval

AIM: To evaluate the quality of life of recruits after refractive surgery. METHODS: Population-based, cross-sectional study. Using the Quality of Life Impact of Refractive Correction (QIRC) questionnaire, the quality of life in 615 recruits underwent refractive surgery was evaluated. The overall score and each question score of QIRC were compared between subgroups of different strength of preoperative refractive error, postoperative interval, type of surgical procedure and postoperative recovery. RESULTS: The mean overall QIRC score of recruits underwent refractive surgery was 49.15±7.89. Significant difference was found for strength of preoperative refractive error (F=4.16, P<0.05), with the low myopia group (50.67±7.59) had significantly better scores than those with high myopia (47.57±7.52, F=4.16, P<0.05). Recruits after a postoperative interval no more than 6mo (49.18±7.86) scored equally to those of more than 6mo (49.18±8.03). Recruits underwent surface ablation surgery scored lowest (46.68±6.09), but showed no significant difference when compared with all underwent refractive surgery (t=1.99, P>0.05). Scores of recruits underwent mechanical microkeratome laser in situ keratomileusis (MK-LASIK), Sub-Bowman’s keratomileusis (SBK), femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK), femtosecond lenticule extraction (ReLEx flex) or small-incision lenticule extraction (ReLEx SMILE) procedure showed no significant difference too. Recruits had adverse complaints postoperatively (45.85±6.66) scored lower when compared with all underwent refractive surgery (t=5.28, P<0.01). CONCLUSION: The quality of life of recruits after refractive surgery was good except those with postoperative complications. Preoperative low myopia recruits had better quality of life than medium and high myopia ones.

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