Injection Of Phosphate Research Articles

Intraocular amphiregulin and axial elongation in non-human adolescent primates

The purpose of the experimental interventional study was to examine the influence of intraocularly applied amphiregulin, a member of the epidermal growth factor (EGF) family, on axial length in young non-human primates. It included three non-human primates (Macaca mulatta), aged 4–6 years. The left eyes received three intravitreal injections of amphiregulin (400ng/50 μl) in intervals of 4 weeks, while the right eyes received three intravitreal injections of phosphate buffered solution (50 μl) at the same time points. Ocular biometry was performed in weekly intervals. At baseline, the left eyes (study eyes) were shorter than the right (control) eyes (20.69 ± 0.21 mm versus 20.79 ± 0.24 mm; P < 0.001), with an inter-eye axial length (AL) difference (left minus right eye) of −0.10 ± 0.23 mm. Inter-eye AL difference increased (P < 0.001) to 0.15 ± 0.18 mm at study end, at 12 weeks after baseline. Axial elongation during the study was higher (P < 0.001) in the left eyes (20.69 ± 0.21 mm to 21.05 ± 0.29 mm or 0.36 ± 0.30 mm) than in the right eyes (20.79 ± 0.24 mm to 20.90 ± 0.31 mm or 0.11 ± 0.17 mm). In a parallel manner, inter-eye difference in vitreous cavity depth combined with lens thickness (left eye minus right eye) increased from −0.04 ± 0.17 mm at baseline to −0.02 ± 0.21 mm (P = 0.02), 0.04 ± 0.10 mm (P = 0.002), and to 0.42 ± 0.67 mm (P < 0.001) at 5, 6, and 12 weeks after baseline, respectively. The results suggest that intravitreally applied amphiregulin as EGF family member led to an increase in axial length in adolescent non-human primates. It supports the hypothesis of amphiregulin as EGF family member being involved in the process of axial elongation.

Pharmacokinetics of Dexamethasone in Children and Adolescents with Obesity.

Dexamethasone is a synthetic glucocorticoid approved for treating disorders of various organ systems in both adult and pediatric populations. Currently, approved pediatric dosing recommendations are weight-based, but it is unknown whether differences in dexamethasone drug disposition and exposure exist for children with obesity. This study aimed to develop a population pharmacokinetic (PopPK) model for dexamethasone with data collected from children with obesity. Dexamethasone was given as either IV or oral/enteral administration, and a salt factor correction was used for dexamethasone sodium phosphate injection. A PopPK analysis using dexamethasone plasma concentration versus time was performed using the software NONMEM. A virtual population of 1000 children with obesity across three age groups was generated for dosing simulations. Data from 59 study participants with 82 PK plasma samples were used in the PopPK analysis. A one-compartment model with first-order absorption and the inclusion of total body weight as a covariate characterized the data. No other covariates were included in the PopPK model. Single and multiple IV dose(s) of 0.5 and 1 mg/kg every 8 h resulted in 68% or more of virtual children with obesity attaining simulated exposures that were within exposure ranges previously reported in adult studies. In conclusion, this was the first study to characterize dexamethasone's PopPK in children with obesity. Simulation results suggest that virtual children with obesity receiving oral doses of 0.5 and 1 mg/kg had generally comparable dexamethasone exposures as adult estimates. Additional studies are needed to characterize the dexamethasone's target exposure in children.

Pioglitazone Antagonized the Effects of Advanced Glycation End Products on Achilles Tendon Healing and Improved the Recovery of Tendon Biomechanical Properties.

Advanced glycation end products (AGEs) often accumulate in the Achilles tendon during the course of diabetes. This study aims to determine the impact of AGEs on tendon repair and explore the role of pioglitazone in mitigating this impact. Forty-eight male 8week-old Sprague Dawley rats were selected in this study. After transection of Achilles tendon, the rats were randomly divided into four groups. The Achilles tendons of rats were injected with 1000mmol/L D-ribose to elevate the content of AGEs within the tendons in two groups, the remaining two groups received injections of phosphate buffered saline (PBS) solution. Subsequently, the first two groups were respectively received oral administration of pioglitazone (20mg/kg/day) and PBS. The remaining two groups were given the same treatment. The expression of the collagen-I, TNF-α, IL-6 of the repaired tendon were detected. The macroscopic, pathologic and biomechanical aspects of tendon healing were also evaluated. AGEs accumulation in tendon during the healing process increases the expression of inflammatory factors such as TNF-α and IL-6, leading to insufficient synthesis of collagen-I and delayed recovery of the tendon's tensile strength. Pioglitazone significantly attenuated the damage caused by AGEs to the tendon healing process, effectively improving the recovery of tendon tensile strength. Pioglitazone could not inhibit the generation of AGEs in the tissue and also had no impact on the normal healing process of the tendon. Pioglitazone could prevent the deleterious impact of AGEs on the Achilles tendon healing and improve the biomechanical properties of the tendon.

Stromal cell-derived factor-1 alpha improves cardiac function in a novel diet-induced coronary atherosclerosis model, the SR-B1ΔCT/LDLR KO mouse

Background and aimsThere are a limited number of pharmacologic therapies for coronary artery disease, and few rodent models of occlusive coronary atherosclerosis and consequent myocardial infarction with which one can rapidly test new therapeutic approaches. Here, we characterize a novel, fertile, and easy-to-use HDL receptor (SR-B1)-based model of atherogenic diet-inducible, fatal coronary atherosclerosis, the SR-B1ΔCT/LDLR KO mouse. Additionally, we test intramyocardial injection of Stromal Cell-Derived Factor-1 alpha (SDF-1α), a potent angiogenic cytokine, as a possible therapy to rescue cardiac function in this mouse. MethodsSR-B1ΔCT/LDLR KO mice were fed the Paigen diet or standard chow diet, and we determined the effects of the diets on cardiac function, histology, and survival. After two weeks of feeding either the Paigen diet (n = 24) or standard chow diet (n = 20), the mice received an intramyocardial injection of either SDF-1α or phosphate buffered saline (PBS). Cardiac function and angiogenesis were assessed two weeks later. ResultsWhen six-week-old mice were fed the Paigen diet, they began to die as early as 19 days later and 50% had died by 38 days. None of the mice maintained on the standard chow diet died by day 72. Hearts from mice on the Paigen diet showed evidence of cardiomegaly, myocardial infarction, and occlusive coronary artery disease.For the five mice that survived until day 28 that underwent an intramyocardial injection of PBS on day 15, the average ejection fraction (EF) decreased significantly from day 14 (the day before injection, 52.1 ± 4.3%) to day 28 (13 days after the injection, 30.6 ± 6.8%) (paired t-test, n = 5, p = 0.0008). Of the 11 mice fed the Paigen diet and injected with SDF-1α on day 15, 8 (72.7%) survived to day 28. The average EF for these 8 mice increased significantly from 48.2 ± 7.2% on day 14 to63.6 ± 6.9% on day 28 (Paired t-test, n = 8, p = 0.003). ConclusionsThis new mouse model and treatment with the promising angiogenic cytokine SDF-1α may lead to new therapeutic approaches for ischemic heart disease.

(275) IGFBP5 Short Hairpin RNA (shRNA) Constructs Improve Erectile Function in a Mouse Model of Cavernous Nerve Injury

Abstract Introduction Radical prostatectomy for prostate cancer not only induces cavernous nerve injury but also causes cavernous angiopathy, which is responsible for poor responsiveness to phosphodiesterase-5 inhibitors. Insulin-like growth factor-binding protein 5 (IGFBP5) promotes cell death and induces apoptosis in various cell types. Objective To investigate the effectiveness of IGFBP5 knockdown at improving erectile function in a mouse model of cavernous nerve injury. Methods Eight-week-old C57BL/6 mice were used to prepare cavernous nerve injury model. Mice were divided into 4 groups: a sham operation group and three cavernous nerve injury (CNI) groups, which were administered intracavernous injections of phosphate buffered saline, scrambled control shRNA, or shRNA targeting mouse IGFBP5 (shIGFBP5) lentivirus particles. One week later, we measured erectile function by electrically stimulating the bilateral cavernous nerve. Results IGFBP5 expression in cavernous tissues were significantly increased in CNI mice compare to sham mice. CNI mice had reduced erectile function, but shIGFBP5 treatment resulted in significant improvements. Furthermore, in CNI mice, numbers of cavernous endothelial cells, pericytes, and neuronal cells were increased by shIGFBP5 treatment. Conclusions Knockdown of IGFBP5 improved erectile function in CNI mice by enhancing neurovascular regeneration. Local inhibition of IGFBP5 expression may provide a new treatment strategy for the treatment of neurovascular diseases. Disclosure No.

PERBANDINGAN KADAR DAN UJI MUTU FISIK INJEKSI DEXAMETHASONE SODIUM PHOSPHATE SEBELUM DAN SESUDAH MASA KADALUARSA SECARA SPEKTROFOTOMETRI UV-VIS

Corticosteroids are drugs that contain synthetic steroid hormones. Dexamethasone sodium phosphate injection is a sterile preparation where a sterile preparation when opened will be exposed to air and microorganism in the surrounding environment, so that drug levels and potency will decrease. The use of steroid injection includes the use that is often used in hospitals and makes stock increase, this increase in preparations which often makes expired preparations will increase and become a problem in every hospital. This study aimed to determine the effect of storage at room temperature and refrigerator temperature on the level and physical quality of dexamethasone sodium phosphate injection before and after expiration. This study used dexamethasone sodium phosphate injection before and after expiration. The raw material for dexamethasone sodium phosphate is listed on the COA, 2022. The injection was stored at room temperature (&lt;300C) and refrigerator temperature (2-80C) within 14 days, then organoleptic observation, pH test, and assay were carried out using UV-VIS Spectrophotometry. Quantitative analysis was carried out by comparing the levels of dexamethasone injection before and after the expiration date based on the linear regression chart and the paired sample t-test. The results obtained show that storage at room temperature and refrigerator temperature does not affect organoleptic observations, pH at the levels of dexamethasone sodium phosphate injection before and after expiration. Testing of dexamethasone sodium phosphate injection levels before and after expiration at room temperature storage (&lt;300C) did not have a significant difference, while dexamethasone sodium phosphate injection levels before and after expiration at refrigerator temperature storage (2-80C) had a significant difference.

Synergistic effects of electroacupuncture and bone marrow mesenchymal stem cell transplantation on rat intrauterine adhesion： an observation.

To investigate the effects of electroacupuncture(EA) combined with bone marrow mesen-chymal stem cells(BMSCs) transplantation on the endometrium of rats with intrauterine adhesions(IUA), so as to explore the possible mechanisms underlying their combined therapeutic effects. Forty adult female SD rats were randomly divided into control, model, cell, and combined groups. The IUA rat model was established using a dual injury method of mechanical scratching and lipopolysaccharide infection. After successful modeling, on days 1, 3, and 7, rats in the model group received tail vein injection of phosphate buffered solution, while rats in the cell group received tail vein injection of BMSCs suspension for BMSCs transplantation；and rats in the combined group received BMSCs transplantation combined with EA treatment (2 Hz/15 Hz, 1-2 mA), targeting the "Guanyuan"(CV4), bilateral "Zusanli"(ST36) and "Sanyinjiao"(SP6) for 20 min daily for 3 consecutive estrous cycles. After intervention, uterine tissue was collected from 5 rats in each group. Histological analysis was performed using hematoxylin and eosin staining to evaluate endometrial thickness and glandular number. Masson staining was used to assess endometrial fibrosis area. Immunohistochemistry was performed to detect the positive expressions of vascular endothelial growth factor(VEGF), proliferating cell nuclear antigen(PCNA), and estrogen receptor(ER). Western blot analysis was conducted to determine the protein expressions of homeobox A10(HoxA10) and leukemia inhibitory factor(LIF), both key regulators of endometrial receptivity. The remaining 5 rats in each group were co-housed with male rats, and the uterine function recovery was evaluated by assessing the number of embryo implantations. Compared with the control group, the model group showed thinning endometrium(P<0.001), decreased glandular number(P<0.001), increased endometrial fibrosis area(P<0.001), reduced positive expressions of VEGF, PCNA, ER, expressions of HoxA10 and LIF, and decreased embryo implantation number (P<0.001) on the injured side of the uterus. Compared with the model group, the combined group showed a reversal of the aforementioned indicators(P<0.001, P<0.01)；the cell group exhibited thicker endometrium(P<0.001) and reduced endometrial fibrosis area(P<0.001). Compared with the cell group, the combined group showed increased endometrial thickness(P<0.01), elevated glandular number(P<0.05), significantly decreased endometrial fibrosis area(P<0.05), enhanced positive expressions of VEGF, PCNA and ER, expressions of HoxA10 and LIF in the endometrium, and a significant increase in embryo implantation number (P<0.001, P<0.05, P<0.01) on the injured side of the uterus, indicating better results than the cell group. The combination of EA and BMSCs synergistically promotes the repair of damaged endometrium, improves endometrial morphology, reduces fibrosis levels, enhances vascular regeneration and matrix cell proliferation, improves endometrial receptivity, which ultimately facilitates embryo implantation.

MicroRNA-148a-3p in pericyte-derived extracellular vesicles improves erectile function in diabetic mice by promoting cavernous neurovascular regeneration

BackgroundTo investigate the regulatory role of microRNA (miR)-148a-3p in mouse corpus cavernous pericyte (MCPs)-derived extracellular vesicles (EVs) in the treatment of diabetes-induced erectile dysfunction (ED).MethodsMouse corpus cavernous tissue was used for MCP primary culture and EV isolation. Small-RNA sequencing analysis was performed to assess the type and content of miRs in MCPs-EVs. Four groups of mice were used: control nondiabetic mice and streptozotocin-induced diabetic mice receiving two intracavernous injections (days − 3 and 0) of phosphate buffered saline, MCPs-EVs transfected with reagent control, or MCPs-EVs transfected with a miR-148a-3p inhibitor. miR-148a-3p function in MCPs-EVs was evaluated by tube-formation assay, migration assay, TUNEL assay, intracavernous pressure, immunofluorescence staining, and Western blotting.ResultsWe extracted EVs from MCPs, and small-RNA sequencing analysis showed miR-148a-3p enrichment in MCPs-EVs. Exogenous MCPs-EV administration effectively promoted mouse cavernous endothelial cell (MCECs) tube formation, migration, and proliferation, and reduced MCECs apoptosis under high-glucose conditions. These effects were significantly attenuated in miR-148a-3p-depleted MCPs-EVs, which were extracted after inhibiting miR-148a-3p expression in MCPs. Repetitive intracavernous injections of MCPs-EVs improved erectile function by inducing cavernous neurovascular regeneration in diabetic mice. Using online bioinformatics databases and luciferase report assays, we predicted that pyruvate dehydrogenase kinase-4 (PDK4) is a potential target gene of miR-148a-3p.ConclusionsOur findings provide new and reliable evidence that miR-148a-3p in MCPs-EVs significantly enhances cavernous neurovascular regeneration by inhibiting PDK4 expression in diabetic mice.

Evaluation of a steroid delivery system to mitigate the severity of proliferative vitreoretinopathy in a minipig model.

To investigate the efficacy of liposomal prednisolone phosphate to mitigate the severity of proliferative vitreoretinopathy (PVR) in a minipig model of PVR. A total of 18 eyes of 9 minipigs underwent PVR induction surgically. Eyes were randomized equally into three groups: intravitreal injection of liposomal prednisolone phosphate (LPP), triamcinolone acetonide (TA), and controls. PVR severity was graded on fundoscopic examination using a modified version of the Silicon Study Classification System. Severe PVR was defined as grade 2-5 on this classification, and the proportion of eyes with retinal detachment from severe PVR, defined as retinal re-detachment, i.e., PVR grade 2-5, was compared between treatment and control groups. On day 28, five eyes (83.3%) in the control group were observed to have severe PVR. Within the LPP group, one (16.7%) eye developed retinal detachment due to severe PVR. Grade 0 PVR was observed in four (66.7%) eyes, grade 1 in one (16.7%) eye, and grade 5 in one (16.7%) eye. Within the TA group, grade 0 PVR was observed in four eyes (66.7%), grade 1 in two eyes (16.6%), and grade 5 in one (16.7%) eye. The difference in the proportion of eyes with severe PVR was significantly lower in the LPP group compared to controls at day 28 (16.7% vs 83.3%, p=0.02). There was no significant difference in the rate of severe PVR or median PVR grade between the liposomal prednisolone phosphate and triamcinolone acetonide groups. Liposomal prednisolone phosphate reduces the severity of PVR in a minipig model of PVR.

Preparation of core-shell composite materials capable of slowly releasing phosphate and their remediation performance of uranium-contaminated groundwater

Acid in-situ leach uranium mining significantly alters the geochemistry of the ore zone, and leaves uranium, residual acid, as well as other potential contaminants in groundwater, which bring harm to human health and ecological environment. Many investigators have been trying to propose remediation strategies for the uranium-contaminated groundwater. Phosphate is an effective immobilization reagent of uranium in the groundwater. However, direct injection of phosphate tends to quickly form precipitates, resulting in fast blockage of the seepage passages in the ore zone around the injection holes and hindering its diffusion. In this paper, HAP@SiO2-600, HAP@SiO2-600@25SA, and HAP@SiO2-600@75SA with core-shell structures were prepared. Their slow-release of phosphate, the effects of pH, contact time, initial uranium concentration, and coexisting ions on their removal rate and efficiency of uranium, and their function of remediating uranium-contaminated groundwater were investigated. It was found that the increase of SA content in the outer layer of HAP@SiO2-600@25SA and HAP@SiO2-600@75SA resulted in the slow release rate of phosphate, decreasing the removal rate of uranium. The adsorption capacities of HAP@SiO2-600, HAP@SiO2-600@25SA, and HAP@SiO2-600@75SA from the aqueous solution at pH = 3.0 and 303 K were up to 582.6, 558.5, and 507.3 mg g−1, respectively. In addition, the materials showed excellent uranium removal performance in experiments where multiple ions coexisted. For actual acidic uranium-contaminated groundwater, HAP@SiO2-600, HAP@SiO2-600@25SA, and HAP@SiO2-600@75SA effectively increased the pH from 2.75 to 4.40, 3.87, and 3.72, respectively, and decreased the uranium concentration from 5.12 to 0.0062, 0.0065, and 0.0058 mg L−1, respectively. The FT-IR, XRD, TEM and XPS characterizations were performed to further clarify the uranium removal mechanism, and it was found that the elimination of U(VI) was ascribed to dissolution-precipitation, adsorption and ion exchange. The results show that the core-shell composite material capable of slowly releasing phosphate is effective in remediating uranium-contaminated groundwater.

IFN-γ enhances the therapeutic efficacy of MSCs-derived exosome via miR-126-3p in diabetic wound healing by targeting SPRED1.

The traditional treatment of diabetic wounds is unsatisfactory. Exosomes isolated from bone marrow mesenchymal stem cells (BMSCs) promote the healing of diabetic wounds. However, whether the exosomes secreted by interferon (IFN)-γ-pretreated BMSCs have an enhanced therapeutic effect on diabetic wound healing and the relevant mechanisms remain unclear. In this study, we isolated exosomes from the corresponding supernatants of BMSCs with (IExos) or without IFN-γ treatment (NExos). Human umbilical vein endothelial cells (HUVECs) were used to investigate the proliferation, migration, and tube formation under different treatments in vitro. Diabetic mice were induced by intraperitoneal administration of streptozotocin, and a circular full-thickness dermal defect was then made on the back of each mouse, followed by a multisite subcutaneous injection of phosphate buffered saline or exosomes. Hematoxylin-eosin (H&E) staining, Masson's trichrome staining, and histological analysis were performed to assess the speed and quality of wound healing. NExos treatment accelerated the healing of diabetic wounds by promoting angiogenesis in vivo and in vitro, and IExos exhibited superior therapeutic efficiency. MicroRNA (miR)-126-3p was significantly increased in IExos, and exosomal miR-126-3p promoted angiogenesis and diabetic wound healing via its transfer to HUVECs. miR-126-3p regulates SPRED1 by directly targeting the 3'-UTR. Mechanistically, IFN-γ-pretreated BMSCs secreted miR-126-3p-enriched exosomes, which enhanced the function of HUVECs and promoted angiogenesis via the SPRED1/Ras/Erk pathway. Exosomal miR-126-3p secreted from IFN-γ-pretreated BMSCs exhibited higher therapeutic efficacy than NExos in diabetic wound healing by promoting angiogenesis via the SPRED1/Ras/Erk axis.

Total Knee Conversion Rates and Functional Outcome After Calcium Phosphate Injection for Bone Marrow Lesions of the Knee.

Untreated osteoarthritis (OA)-related bone marrow lesions (OA-BML) can hasten the progression of knee OA. Previous studies have shown that fluoroscopically guided intraosseous calcium-phosphate (CaP) injections of OA-BML during knee arthroscopy can lead to pain reduction, improved functionality, and prolonged time until conversion to total knee arthroplasty (TKA). The purpose of this retrospective study is to compare the clinical outcomes of patients who underwent knee arthroscopy and CaP injection for OA-BML versus knee arthroscopy for non-OA-BML pathologies. Two-year follow-up data and patient-reported outcomes including knee injury and operative outcome scores, joint replacement scores (KOOS, JR) were available for 53 patients in the CaP group and 30 patients in the knee arthroscopy group. Results indicate that patients in the CaP group had less frequent conversion to TKA compared with patients in the knee arthroscopy group. Statistical analysis demonstrated a statistical difference between preoperative and postoperative KOOS, JR within the CaP group but not for the knee arthroscopy group. Two-year postoperative KOOS, JR for CaP patients was statistically greater than the 2-year postoperative KOOS, JR of knee arthroscopy patients. Results indicate greater improvement in functional outcomes with knee arthroscopy and CaP injection of OA-BML compared with knee arthroscopy alone for non-OA-BML diagnoses. The results of this retrospective study help to distinguish the benefits of knee arthroscopy accompanied by CaP intraosseous injection from that of knee arthroscopy alone.

Initial Experience With Subchondral Stabilization for Grade II Stress Fractures of the Midfoot and Forefoot

Stress fractures of the foot are often preceded by magnetic resonance imaging evidence of bone marrow edema. While new evidence suggests intraosseous injection of calcium phosphate ("subchondral stabilization") can alleviate symptoms associated with bone marrow edema, no data yet exist regarding its use in developing mid- and forefoot stress fractures. Fifty-four patients who underwent subchondral stabilization of various midfoot/forefoot bones in our practice were observed over a 5-year period. All patients were unresponsive to standard nonoperative measures for at least 6 weeks, and all had clinical exams and advanced imaging consistent with a Kaeding-Miller Grade II stress fracture. Forty patients were included with a mean age of 54.3 ± 14.9 years and mean follow-up of 14.1 ± 6.9 months. Patients saw a significant decrease in visual analog scale (VAS) pain as early as 1 month postoperatively (p < .05). Mean postoperative VAS at 12 months was 2.11 ± 2.50, and mean reduction in VAS pain from preoperative to 12 months postoperative was -5.00 (95% CI -3.44 to -6.56, p < .05). Fourteen patients (34%, 14/41) were entirely pain free at 12 months. Higher preoperative VAS pain scores (unadjusted odds ratio [OR] 2.13 [95% CI 1.20-3.77], p=.010) and treatment of more than 1 bone (unadjusted OR 6.23 [95% CI 1.39-27.8], p=.017) were associated with a greater likelihood of not achieving a pain free status at 12 months. Our initial experience with subchondral stabilization suggests the procedure may be safe and effective for use in many Kaeding-Miller Grade II stress fractures of the mid- and forefoot.

Route of dexamethasone administration influences parasite burden in Strongyloides hyperinfection model.

Rodents infected with Strongyloides venezuelensis are experimental models applied to strongyloidiasis research. This study evaluated oral and subcutaneous dexamethasone (DEX) treatments to establish immunosuppression in an experimental model of Strongyloides hyperinfection. Rattus norvegicus Wistar were divided: G I (-): untreated and uninfected animals, G II (+): untreated and infected, G III (o -) orally treated and uninfected, G IV (o +) orally treated and infected, G V (sc -) subcutaneously treated and uninfected, G VI (sc +) subcutaneously treated and infected. For oral administration, DEX was diluted in sterile water (5µg/ml) and made available to the animals on intervals in experimental days - 5-0, 8-13 and 21-26. For subcutaneous administration, animals received daily injections of DEX disodium phosphate (2mg/kg). Infection was established by the subcutaneous inoculation of 3000 S. venezuelensis filarioid larvae. Groups were evaluated by egg per gram of feces and parasite females counts and IgG, IgG1 and IgG2a detection. GIV (o +) had egg peaks count on days 13 and 26 and maintained egg elimination until the last experimental day. Parasitic females recovery at day 30 was significantly higher in G IV (o +) when compared to G VI (sc +). Levels of IgG, IgG1 and IgG2a of all groups, except the positive control GII (+), were below the detection threshold. Pharmacological immunosuppression induced by oral administration of DEX produced high parasitic burden, and is a noninvasive method, useful to establish immunosuppression in strongyloidiasis hyperinfection model in rats.

Microfluidic encapsulation of photosynthetic cyanobacteria in hydrogel microparticles augments oxygen delivery to rescue ischemic myocardium

Cardiovascular disease, primarily caused by coronary artery disease, is the leading cause of death in the United States. While standard clinical interventions have improved patient outcomes, mortality rates associated with eventual heart failure still represent a clinical challenge. Macrorevascularization techniques inadequately address the microvascular perfusion deficits that persist beyond primary and secondary interventions. In this work, we investigate a photosynthetic oxygen delivery system that rescues the myocardium following acute ischemia. Using a simple microfluidic system, we encapsulated Synechococcus elongatus into alginate hydrogel microparticles (HMPs), which photosynthetically deliver oxygen to ischemic tissue in the absence of blood flow. We demonstrate that HMPs improve the viability of S.elongatus during the injection process and allow for simple oxygen diffusion. Adult male Wistar rats (n= 45) underwent sham surgery, acute ischemia reperfusion surgery, or a chronic ischemia reperfusion surgery, followed by injection of phosphate buffered saline (PBS), S.elongatus suspended in PBS, HMPs, or S.elongatus encapsulated in HMPs. Treatment with S.elongatus-HMPs mitigated cellular apoptosis and improved left ventricular function. Thus, delivery of S.elongatus encapsulated in HMPs improves clinical translation by utilizing a minimally invasive delivery platform that improves S.elongatus viability and enhances the therapeutic benefit of a novel photosynthetic system for the treatment of myocardial ischemia.

Influence of discontinuation of prophylactic antimicrobial agent for trabeculectomy

BackgroundThere is no unified view of the necessity of prophylactic antimicrobial agents in trabeculectomy. Preoperative prophylactic antimicrobial agent injection and cefazolin sodium (CEZ) for trabeculectomy were discontinued at the Hiroshima University Hospital. In this study, we evaluated whether discontinuation of preoperative administration of CEZ in ophthalmology affects the incidence of postoperative infections.MethodsWe retrospectively investigated patient background, concomitant medications, subconjunctival dexamethasone sodium phosphate (DEX) injection at the end of the surgery, and the incidence of infective endophthalmitis within 6 weeks after surgery in the CEZ and non-CEZ groups. We also performed propensity score matching for background matching. Statistical analysis was performed using the Mann-Whitney U-test and Fisher’s exact test.ResultsThe incidence of postoperative endophthalmitis was not significantly different between 629 and 751 patients in the CEZ and no-CEZ groups, respectively (0 in the CEZ group and 2 in the no-CEZ group, P = 0.504). More patients in the CEZ group were taking diabetes drugs preoperatively (P = 0.028) and fewer patients were receiving subconjunctival DEX at the end of surgery (P < 0.001) than those in the non-CEZ group. Propensity scores were calculated using the risk factors for postoperative infection as covariates, and matching (580 patients in the CEZ group and 580 patients in the non-CEZ group) showed no significant difference in the incidence of postoperative endophthalmitis (P = 0.500).ConclusionsThere was no significant difference in the incidence of endophthalmitis after trabeculectomy between the CEZ and non-CEZ groups, suggesting a decreased need for CEZ injections before trabeculectomy.

Long-acting acid-sensitive ketal-linked dexamethasone microcrystals for treating experimental autoimmune uveitis.

Corticosteroids have for some time been used as first-line drugs for the topical treatment of noninfectious uveitis, but poor ocular bioavailability and the rapid clearance of eye drops necessitate frequent dosing, reducing patient compliance. In this study, we used an acid-sensitive stearoxyl-ketal-dexamethasone pro-drug microcrystals (SKD MCs), which is consistently safe and effective in the control of uveitis inflammation in rats. We used a rat model of experimental autoimmune uveitis (EAU) to evaluate the effects of SKD MCs in terms of clinical manifestations, molecular biology, pathological histology, and visual electrophysiology compared to dexamethasone sodium phosphate injection or phosphate-buffered saline. SKD MCs significantly reduced inflammation in EAU, improved the ability to suppress inflammatory cytokines and to protect retinal function, and significantly reduced retinal microglia activation, with no increase in intraocular pressure throughout the treatment. Our results indicate that the SKD MCs formulation holds promise as a new strategy for the treatment of noninfectious uveitis and potentially other ocular inflammatory diseases.

Intraoperative subconjunctival steroid reduces the incidence of pseudophakic macular oedema: a cohort study of 20,066 consecutive phacoemulsification surgeries.

Pseudophakic macular oedema remains the most common sight-threatening complication following cataract surgery. This study aims to assess the effect of intraoperative subconjunctival steroids on the rate of pseudophakic cystoid macular oedema. A retrospective, observational database study of 20 066 consecutive phacoemulsification surgeries. The incidence of pseudophakic cystoid macular oedema was compared in eyes that did and did not receive intraoperative subconjunctival steroid injection during routine cataract surgery. Intraoperative subconjunctival injection of dexamethasone or betamethasone sodium phosphate significantly reduced the odds of developing pseudophakic cystoid macular oedema across the cohort (odds ratio: 0.67; 95% confidence interval: 0.46-0.98, p = 0.039). The effect of subconjunctival steroids on pseudophakic macular oedema remained independently associated on multivariate logistic regression analysis (p = 0.028). This study demonstrates that administration of intraoperative subconjunctival steroid injection is associated with a reduced incidence of pseudophakic cystoid macular oedema in routine, uncomplicated cataract surgery.

Intraocular Amphiregulin antibody and axial elongation in nonhuman primates.

To examine the effect of intraocularly applied amphiregulin antibody on physiological axial elongation in young nonhuman primates. The experimental study included six male 12-months-old macaque nonhuman primates (body weight:2.46 ± 0.25kg;range:2.20-2.90kg). In the experimental group (n=3 animals), three intravitreal injections of amphiregulin antibody (100μg/50μl) were applied to the left eyes at intervals of 4-6 weeks, and injections of phosphate buffered solution (50μl) were applied to the right eyes. Three other animals were assigned to a blank control group. During the study period of 23.6 weeks, axial length in the experimental group did not change in the left eyes (18.91 ± 0.37mm to 18.94 ± 0.67mm;P=0.90), while it linearly increased in the right eyes (18.87 ± 0.38mm to 19.24 ± 0.53mm;P=0.056) and in the control group (left eyes:19.15 ± 0.22mm to 19.48 ± 0.22mm;P=0.009; right eyes:19.17 ± 0.15 mm to 19.46 ± 0.23 mm;P=0.024). The interocular difference in axial elongation increased in the experimental group from -0.11 ± 0.12mm at 4 weeks after baseline to -0.34 ± 0.15mm at the study end, while in the control group, the interocular side difference did not change significantly (from 0.01 ± 0.10 mm to 0.03 ± 0.08 mm;P=0.38). The difference in the interocular difference in axial elongation between the two groups was significant at 8 weeks (P=0.01), 15 weeks (P=0.007), and at study end (P=0.02). The interocular difference in axial length correlated with the interocular difference in vitreous cavity length (standardized regression coefficient beta:0.85;P<0.001). The interocular axial length difference was inversely associated with the interocular refractive error difference (beta:-0.49;P<0.001). Intraocularly applied amphiregulin antibody (100μg) reduced the physiological ocular axial elongation in juvenile nonhuman primates.

Multiple Drilling with Recombinant Human Bone Morphogenetic Protein-2 in Korean Patients with Non-Traumatic Osteonecrosis of the Femoral Head: A Prospective Randomized Pilot Study with a Minimum Two-Year Follow-Up.

We sought to determine whether multiple drilling (MD) combined with the injection of recombinant human bone morphogenetic protein-2 (rhBMP-2) and β-tricalcium phosphate (β-TCP) could improve survival of the femoral head in pre-collapse lesions of non-traumatic osteonecrosis of the femoral head (ONFH) as compared with MD alone. We conducted a single-site, off-label, comparative and prospective cohort study between November 2017 and May 2019. We enrolled 25 hips (25 patients) with non-traumatic ONFH (Ficat–Arlet stage 2A or less). We performed a survival analysis, and the primary outcome was the occurrence of femoral head collapse on follow-up radiograph. Our cohort consisted of 11 men and 9 women of age 52.5 ± 8.8 years and a body mass index of 24.3 ± 3.0 kg/m2. The femoral heads were preserved in 9 hips (45.0%) and collapsed in 11 hips (55.0%) at the final follow-up; mean survival to collapse was 6.9 (range 2.8–13.5) months. There were no significant differences in the survival of the femoral head between the MD alone group and the MD with rhBMP-2 and β-TCP group (five hips survived, 50% vs. four hips survived, 40%, respectively; p = 0.83). MD combined with the injection of rhBMP-2 and β-TCP did not improve femoral head survival compared to MD alone in the pre-collapse non-traumatic ONFH lesion.