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Scientific Reports Jul 2022The aim of the present study was to describe foveal eversion patterns in diabetic macular edema (DME) and to assess their relationship with the course of the disease and...
The aim of the present study was to describe foveal eversion patterns in diabetic macular edema (DME) and to assess their relationship with the course of the disease and the outcome. The study was designed as prospective, observational, with two years of follow-up. DME patients were divided in two groups, one treated by combined anti-VEGF injections and dexamethasone (DEX) implants, and the other treated by fluocinolone acetonide (FAc) implant with additional anti-VEGF retreatments if needed. Main outcome measures were foveal eversion prevalence, foveal eversion patterns, best-corrected visual acuity (BCVA), central macular thickness (CMT), structural OCT metrics, number of intravitreal injections. One hundred and forty-six eyes (146 patients; 80 males; mean age 67 ± 8 years) affected by already treated DME, with 84 eyes treated with anti-VEGF/DEX treatments (mean of 10 ± 3 injections) and 62 treated with FAc implant. Looking at the treatments administered before the inclusion into the study, 84 eyes (58%) were treated with anti-VEGF injections, whereas 62 eyes (42%) underwent a combination of anti-VEGF and corticosteroids implants. DME eyes showed statistically significant improvements of LogMAR BCVA and CMT over the 2-year follow-up. Foveal eversion was found in 83 eyes (57%), categorized as follows: Pattern 1a (16;19%); Pattern 1b (22;27%) and Pattern 2 (45;54%). BCVA improvement was detected in all the subgroups, excepting for Pattern 2, which showed also significantly worse structural OCT parameters. Pattern 1b and Pattern 2 were characterized by significantly higher prevalence of persistent DME (64% and 89% of cases, respectively). Foveal eversion patterns were correlated with progressively worse DME outcome. Foveal eversion may be associated to the loss of foveal homeostasis, with consequent poor response to intravitreal treatments and worse DME outcome.
Topics: Aged; Angiogenesis Inhibitors; Dexamethasone; Diabetes Mellitus; Diabetic Retinopathy; Drug Implants; Fovea Centralis; Glucocorticoids; Humans; Intravitreal Injections; Macular Edema; Male; Middle Aged; Prospective Studies; Retrospective Studies; Visual Acuity
PubMed: 35907954
DOI: 10.1038/s41598-022-17555-8 -
Iranian Journal of Basic Medical... Jan 2021Liqui-Mass technology has shown promising advantages in terms of commercial production and formulation manipulation. This study attempts to further explore the potential...
OBJECTIVES
Liqui-Mass technology has shown promising advantages in terms of commercial production and formulation manipulation. This study attempts to further explore the potential of enhanced drug release of effervescent Liqui-Pellet by optimizing certain parameters.
MATERIALS AND METHODS
In the current study, pellets containing co-solvent, naproxen, coating and carrier materials were prepared via extrusion and spheronisation (Liqui-Pellet). Parameters investigated included polysorbate 80 concentration (as a co-solvent), water content and the presence or absence of neusilin US2 as part of the new binary carrier mixture approach.
RESULTS
It was found that the success of the Liqui-Pellet production was determined by the amount of polysorbate 80 and water used, where above a certain limit, agglomeration occurred, and the formulation failed. Liqui-Pellet formulation showed an excellent flow, narrow size distribution and was robust to pass friability testing. The key findings in the investigation were that the Liqui-Pellet was capable of a remarkably fast drug release, and 100% drug release achieved within 20 min at pH 1.2, wherein naproxen has been known to be practically insoluble in such pH.
CONCLUSION
Liqui-Pellets display the potential to enhance explosive dissolution where a combination of effervescent powders and binary carriers with the high surface area were used. Furthermore, X-ray microtomography revealed that the pellets were very uniform and homogenous.
PubMed: 33643578
DOI: 10.22038/ijbms.2020.51697.11729 -
Biomaterials Advances Mar 2022In the present work, nanohydroxyapatites (nHAp) doped with copper and/or zinc ions were investigated for the assessment of its antibacterial activity and...
Investigation of topography effect on antibacterial properties and biocompatibility of nanohydroxyapatites activated with zinc and copper ions: In vitro study of colloids, hydrogel scaffolds and pellets.
In the present work, nanohydroxyapatites (nHAp) doped with copper and/or zinc ions were investigated for the assessment of its antibacterial activity and biocompatibility. Three forms of material with diverse surfaces were tested: nanopowder in colloidal suspension, galactose hydrogel (3,6-Anhydro-α-l-Galacto-β-d-Galactan) scaffold and pellet. The structural and morphological properties of the obtained biomaterials were comprehensively determined by using: XRPD, FT-IR, SEM-EDS, AAS, XPS and EPR techniques. The antimicrobial active ions, mostly Cu, were successfully released from the apatite structure despite the material being suspended in the porous galactose hydrogel matrix. The colloidal solutions of nanohydroxyapatites on bacterial viability revealed moderate activity of Cu-doped materials against Escherichia coli strain and significant activity against Pseudomonas aeruginosa strain. The comparative study of bacterial attachment to the hydrogel and pellet surface indicated that hydrogels were more prone to be colonized by both tested strains. Moreover, an additive of the Cu ion modified bacterial attachment and biofilms forming on nHAp:Cu and nHAp:Cu-Zn materials. In the case of hydrogels, the biofilms were scattered while these forming on other materials were more clumped. The cytotoxicity evaluation of tested biomaterials showed biocompatible properties of both nanomaterial colloidal solutions as well as galactose hydrogel eluates toward normal mouse osteoblast cell lines (7F2) and human chondrocytes (TC28A2) and osteosarcoma cell line (U2OS). The biocompatibility of tested materials was additionally confirmed by conducting a hemolysis assay which showed full hemocompatibility of nanopowder colloidal solutions and galactose-based materials. Furthermore, unaltered red blood cell morphology was visible after a short and long time of incubation with the obtained biomaterials by using confocal laser scanning microscopy (CLSM). The comparison research provided data of 7F2, TC28 and U2OS cell attachment to the galactose hydrogel surface.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Biocompatible Materials; Copper; Drug Implants; Escherichia coli; Galactose; Humans; Hydrogels; Ions; Mice; Spectroscopy, Fourier Transform Infrared; Zinc
PubMed: 35525765
DOI: 10.1016/j.msec.2021.112547 -
Drug Discovery Today Aug 2019Topical eye-drop administration and intravitreal injections are the current standard for ocular drug delivery. However, patient adherence to the drug regimen and... (Review)
Review
Topical eye-drop administration and intravitreal injections are the current standard for ocular drug delivery. However, patient adherence to the drug regimen and insufficient administration frequency are well-documented challenges to this field. In this review, we describe recent advances in intraocular implants designed to deliver therapeutics for months to years, to obviate the issues of patient adherence. We highlight recent advances in monolithic ocular implants in the literature, the commercialization pipeline, and approved for the market. We also describe design considerations based on material selection, active pharmaceutical ingredient, and implantation site.
Topics: Delayed-Action Preparations; Drug Delivery Systems; Drug Implants; Eye; Humans; Ophthalmic Solutions
PubMed: 31173915
DOI: 10.1016/j.drudis.2019.05.031 -
Pflugers Archiv : European Journal of... Sep 2021The second messengers, cGMP and Ca, have both been implicated in retinal degeneration; however, it is still unclear which of the two is most relevant for photoreceptor... (Review)
Review
The second messengers, cGMP and Ca, have both been implicated in retinal degeneration; however, it is still unclear which of the two is most relevant for photoreceptor cell death. This problem is exacerbated by the close connections and crosstalk between cGMP-signalling and calcium (Ca)-signalling in photoreceptors. In this review, we summarize key aspects of cGMP-signalling and Ca-signalling relevant for hereditary photoreceptor degeneration. The topics covered include cGMP-signalling targets, the role of Ca permeable channels, relation to energy metabolism, calpain-type proteases, and how the related metabolic processes may trigger and execute photoreceptor cell death. A focus is then put on cGMP-dependent mechanisms and how exceedingly high photoreceptor cGMP levels set in motion cascades of Ca-dependent and independent processes that eventually bring about photoreceptor cell death. Finally, an outlook is given into mutation-independent therapeutic approaches that exploit specific features of cGMP-signalling. Such approaches might be combined with suitable drug delivery systems for translation into clinical applications.
Topics: Animals; Calcium Signaling; Cell Death; Cyclic GMP; Drug Delivery Systems; Drug Implants; Humans; Nanoparticles; Photoreceptor Cells; Retinal Degeneration
PubMed: 33864120
DOI: 10.1007/s00424-021-02556-9 -
Communications Biology May 2024Beneficial fungi are well known for their contribution to insects' adaptation to diverse habitats. However, where insect-associated fungi reside and the underlying...
Beneficial fungi are well known for their contribution to insects' adaptation to diverse habitats. However, where insect-associated fungi reside and the underlying mechanisms of insect-fungi interaction are not well understood. Here, we show a pellet-like structure on the legs of mealybugs, a group of economically important insect pests. This at-leg pellet, formed by mealybugs feeding on tomato but not by those on cotton, potato, or eggplant, originates jointly from host secretions and mealybug waxy filaments. A fungal strain, Penicillium citrinum, is present in the pellets and it colonizes honeydew. P. citrinum can inhibit mealybug fungal pathogens and is highly competitive in honeydew. Compounds within the pellets also have inhibitory activity against mealybug pathogens. Further bioassays suggest that at-leg pellets can improve the survival rate of Phenacoccus solenopsis under pathogen pressure, increase their sucking frequency, and decrease the defense response of host plants. Our study presents evidences on how a fungi-associated at-leg pellet provides multiple protections for mealybugs through suppressing pathogens and host defense, providing new insights into complex insect × fungi × plant interactions and their coevolution.
Topics: Penicillium; Animals; Hemiptera
PubMed: 38755282
DOI: 10.1038/s42003-024-06287-2 -
Contraception Aug 2020To assess etonogestrel contraceptive implant location and outcomes among women referred for "difficult" removal to a specialist clinic in South Africa. (Review)
Review
OBJECTIVES
To assess etonogestrel contraceptive implant location and outcomes among women referred for "difficult" removal to a specialist clinic in South Africa.
STUDY DESIGN
We performed a retrospective review of cases referred to our clinic for removal of nonpalpable, deep, migrated, or damaged implants, or failed removals from March to August 2017.
RESULTS
Most (n = 68, 92%) of the 74 referrals were nonpalpable in our clinic. We used ultrasound for localization and successfully removed 72 implants (97%) in the outpatient clinic.
CONCLUSION
With proper protocols and equipment, localization and removal of nonpalpable implants can be safely and effectively achieved in an outpatient African setting.
IMPLICATIONS
Access to providers specially trained in ultrasound localization should be available in all settings where implants are offered. Providing timely access to safe and effective implant removals in routine and difficult cases is essential to ensuring that implant programs are in alignment with rights-based, client-centered family planning principles.
Topics: Contraceptive Agents, Female; Desogestrel; Device Removal; Drug Implants; Female; Humans; Referral and Consultation; Retrospective Studies; South Africa
PubMed: 32339484
DOI: 10.1016/j.contraception.2020.04.013 -
European Journal of Pharmaceutical... Dec 2023FDA's initiative Pharmaceutical CGMPs for the 21st century opened the door for introduction of several risk based approaches in pharmaceutical industry. One significant...
FDA's initiative Pharmaceutical CGMPs for the 21st century opened the door for introduction of several risk based approaches in pharmaceutical industry. One significant advancement that has emerged is the implementation of process analytical technology (PAT), which has opened doors for understanding and controlling complex technological processes. Two such processes, radial extrusion and pellet coating, offer a solid foundation for the application of PAT tools due to their numerous critical process parameters. The aim of the first part of the study was to optimize the neutral pellet production to produce the pellets with properties desired for successful film coating using design of experiments (DoE). In the second part the optimized pellets underwent film coating and the coating quantity was predicted in real or near real-time using in-line and at-line NIR probes and the performance of both probes was compared. The desired properties of the pellets, narrow particle size distribution, high sphericity and high process yield, were successfully achieved. Models for film coating quantity prediction using in-line and at-line NIR probe were successfully calibrated and tested by coating two additional batches. Despite the limited sample size for model calibration, at-line NIR exhibited excellent prediction performance and enabled accurate determination of process end-point. The coating quantity determined by UV/VIS spectroscopy in both test batches deviated by less than 2.0 % from the target value. However, the in-line NIR probe, primarily due to its inferior spectral resolution, displayed a slightly lower quality of the calibrated model and notable overprediction for the tested batches.
Topics: Spectroscopy, Near-Infrared; Technology, Pharmaceutical; Technology; Drug Implants; Drug Industry
PubMed: 37770005
DOI: 10.1016/j.ejps.2023.106595 -
Scientific Reports Apr 2023Bedding material is a crucial environmental factor for chickens. Coffee husks are waste from the industry that could be reused. The study aimed to analyze the chemical...
Bedding material is a crucial environmental factor for chickens. Coffee husks are waste from the industry that could be reused. The study aimed to analyze the chemical composition of various bedding types and assess their impact on the performance characteristics of broiler chickens and the incidence of footpad dermatitis (FPD). Ross 308 broilers were used in the study. Birds were divided into 3 groups (216 chickens, 72 per group). Group 1 was kept on chopped straw (S). Group 2 was kept on coffee husks (CHs), and the 3rd group (PB) was kept on pellet bedding made from S and CHs in a 1:1 ratio. The dry matter (DM), crude fiber (CF), nitrogen (N), phosphorus (P), potassium (K) content, and the pH of the bedding were analyzed. Production results were examined during 42 days of rearing. FPD was assessed on a point scale. The tissue composition of the carcasses and qualitative physicochemical characteristics of the meat (pH, color, water holding capacity, drip loss) and bone-breaking strength were analyzed. Straw had a higher CF content. In total, the highest N content in CHs was noticed. P content was lower in the S, and K was the highest in the CHs group, followed by S and PB. The pH of the bedding was lower in the CHs group, higher in PB, and highest in S bedding. The DM was decreasing within the days of rearing. A significant interaction was demonstrated between the type of bedding and rearing days on the bedding (manure) composition. On days 1-14, FCR deteriorated in the PB group compared to the S group. The presence of FPD was significantly lower in the PB group than in the others. In the PB group, chickens had a higher slaughter yield than in the S group and a lower weight and liver share than in the CHs group. The weight and proportion of abdominal fat were higher in the group kept on S than on CHs. It can be concluded that coffee husks as a component of pellets had a beneficial effect on reducing FPD in chickens and their slaughter yield and enriched bedding with nutrients, which with poultry manure, could be a good fertilizer for agricultural soils after rearing. It could be recommended to use pelleted bedding.
Topics: Animals; Chickens; Coffea; Manure; Housing, Animal; Floors and Floorcoverings; Foot Diseases
PubMed: 37088790
DOI: 10.1038/s41598-023-33859-9 -
Molecules (Basel, Switzerland) Dec 2022This work aimed to develop a new one-pot and readily scaled-up formulation capable of retaining 5-fluorouracil and prolonging its release to obtain a site-specific...
This work aimed to develop a new one-pot and readily scaled-up formulation capable of retaining 5-fluorouracil and prolonging its release to obtain a site-specific medication delivery for the potential treatment of colorectal cancer. Six polymer-based formulations were successfully produced using a thermal bulk polymerization method and loaded with 5-fluorouracil, which is a chemotherapeutic agent used in the treatment of colorectal carcinoma. The pellets produced were characterized by measuring the glass transition temperature, tensile strength, Young's modulus, and tensile elongation at break. Studies on in vitro swelling and release were carried out in phosphate-buffered saline to evaluate the behaviour of the developed system. The Young's modulus, glass transition temperature, and tensile strength all increased significantly as the crosslinker concentration increased, but the fracture strain value reduced significantly. The in vitro swelling profile of the produced formulations was significantly reduced by increasing crosslinking density. Less than 27% cumulative drug release was achieved for all formulations after 5 h of starting the release study. The highest cumulative drug release reached after 24 h was 69%. The developed drug delivery system demonstrated the ability to delay the release of 5-fluorouracil in upper gastrointestinal tract-mimicking conditions, while permitting its release in a controlled way afterward, which makes it promising for the potential delivery of 5-fluorouracil to the colon.
Topics: Fluorouracil; Drug Delivery Systems; Drug Implants; Polymers; Colon
PubMed: 36615499
DOI: 10.3390/molecules28010306