Topical delivery of urea encapsulated in biodegradable PLGA microparticles: O/W and W/O creams

This study describes the formulation and characterization of O/W and W/O creams containing urea-loaded microparticles prepared with poly (D, L-lactic-co-glycolic acid) (PLGA) in order to encapsulate and stabilize urea. The solvent evaporation method was used for preparing PLGA microparticles containing urea. The microparticles size was evaluated by laser light diffractometry. The resulting microparticles were then incorporated in O/W and W/O creams and stability and the release pattern from the creams was evaluated by UV-spectrophotometry. The particle size of PLGA microparticles was in the range of 1-5 microm and most microparticles had a particle size smaller than 3 microm. The encapsulation efficiency was calculated as 40.5% +/- 3.4. This study also examined release pattern of urea which varied among different formulations. The results showed that the release from O/W creams followed Higuchi kinetics while the release from W/O creams showed the zero order kinetics and the creams containing microparticulated urea had slower release than free urea creams.     

糖尿病患者行包皮环切缝合器手术可行性分析

目的探讨糖尿病患者采用包皮环切缝合器手术的可行性。 方法回顾性研究南京医科大学附属明基医院苏州院区2019年12月至2022年2月收治的行包皮环切术的89例糖尿病患者病历资料。依据切除包皮的手术方式不同,分为包皮环切缝合器手术组(n＝36)、传统包皮环切手术组(n＝53)。患者入院后完善术前常规化验和检查,控制血糖,包皮环切缝合器手术组患者术中选择相应型号的一次性包皮环切缝合器切割、缝合包皮;传统包皮环切手术组患者术中距离冠状沟0.5~1.0 cm处用组织剪剪去多余包皮,电刀严密止血后用可吸收线间断缝合。2组患者均用纱布和弹力绷带加压包扎伤口。术后2组患者均予以口服第2代头孢菌素类抗生素3 d预防感染,术后第1天予以更换纱布和弹力绷带,之后每2 d更换1次,直至伤口愈合拆除纱布和弹力绷带为止。比较2组患者平均手术时间、平均术中出血量、术后并发症以及记录包皮环切缝合器手术组吻合器损伤龟头例数。数据行Mann-Whitney U检验、χ²检验和Fisher确切概率法检验。 结果包皮环切缝合器手术组患者平均手术时间[10.0(6.3,14.8) min]和平均术中出血量[1.0(1.0,2.0) mL]显著短于及少于传统包皮环切手术组[28.0(23.0,33.0)min、2.0(1.0,5.0) mL],差异均有统计学意义(Z＝-7.787、-3.884,P<0.05)。术后包皮环切缝合器手术组伤口瘀斑8例(22.2%),高于传统包皮环切手术组[2例(3.8%)],差异有统计学意义(χ²＝5.583,P＝0.018)。包皮环切缝合器手术组术后伤口血肿5例(13.9%)、伤口感染5例(13.9%)、伤口全部裂开5例(13.9%),与传统包皮环切手术组(0、0、0)比,差异均有统计学意义(P＝0.009、0.009、0.009)。包皮环切缝合器手术组术后未出现伤口局部裂开,与传统包皮环切手术组[1例(1.9%)]比较,差异无统计学意义(P＝0.596)。伤口瘀斑较为常见可自行消退;增加弹力绷带层数基础上加压包扎2 d伤口血肿消失;针对伤口感染、伤口全部裂开,予以拆除全部包皮吻合器的钉和硅胶垫片后消毒、包扎,待伤口感染控制后,用可吸收线重新缝合;针对伤口局部裂开应用苯扎氯铵局部消毒。包皮环切缝合器手术组患者术中均未出现吻合器损伤龟头。 结论术前经过严格筛选和沟通后的糖尿病患者行包皮环切缝合器是安全可行的,而且具有手术便捷和手术体验较好等优点。     

Evaluation of direct intramural injection to the bladder wall as a method for developing orthotopic tumor models

BackgroundBladder cancer poses a great burden on society and its high rate of recurrence and treatment failure necessitates use of appropriate animal models to study its pathogenesis and test novel treatments. Orthotopic models are superior to other types since they provide a normal microenvironment. Four methods are described for developing bladder cancer models inside the animal''s bladder. Direct intramural injection is one of these methods and is widely used. However, its efficacy in model development has not yet been studied. We aimed to evaluate the efficacy and success rate of the direct intramural injection method of developing an orthotopic model for the study of bladder cancer.MethodTumor cell lines were prepared in four microtubes. Aliquots of 200 × 10³ cells were injected through a 27 gauge needle into the ventral wall of the bladders of 4 male and 4 female BALB/c mice following a midline 1 cm laparotomy incision. In addition, 1 million cells from each microtube were injected into the flanks of control mice. To prevent infection and alleviate pain, 5 mg/kg enrofloxacin and 2.5 mg/kg flunixin meglumine, respectively, were injected subcutaneously.ResultsTumors formed in all mice, resulting in 100% take rate and zero post‐operation mortality. Surgery time was ≤15 min per mouse. In two mice, tumors were found in the peritoneal space as well.ConclusionDirect intramural injection is a rapid, reliable, and reproducible method for developing orthotopic models of bladder cancer. It can be done on both male and female mice and only requires readily available surgical tools. However, needle track can result in cell spillage and peritoneal tumors.     

Sodium-glucose cotransporter 2 inhibitors: A comprehensive review from cells to bedside

Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2is) are oral medications approved for type 2 diabetes mellitus. Interestingly, during recent years, they have been promisingly considered as new medications for cardiovascular and kidney diseases. However, the mechanisms underlying these new benefits are not fully understood. Thanks to the discovery of multiple modes of action, the simple picture about mechanisms of action of SGLT2is has become more and more complex. Besides their effects in diabetes, there is increasing evidence for their beneficial effects in heart failure and chronic kidney diseases. In addition, many studies have provided evidence for the fruitful effects of SGLT2is in atherosclerotic cardiovascular disease. In this study, we present mounting evidence for the complex action modes of SGLT2is and their current applications in clinical practice.     

The effect of green cardamom on blood pressure and inflammatory markers among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized clinical trials

Research shows that herbal spices, including seeds of Elettaria cardamomum, may exert beneficial effects on unhealthy metabolic status. This study is a systematic review of the effect of green cardamom in patients with metabolic syndrome and its related disorders. PubMed/Medline, Scopus, EMBASE, Web of Science, and Cochrane Library were searched to identify the relevant randomized clinical trials. The data were pooled using the random-effects model, and weighted mean difference (WMD) was considered as summary effect size. Of 625 clinical trials, eight reports with 595 patients (299 in intervention group and 296 in control group) were included. The findings indicated that green cardamom significantly decreased diastolic blood pressure (WMD: −0.91 mmHg, 95%CI; −1.19, −0.62), high-sensitivity C-reactive protein (WMD: −1.21 mg/L, 95%CI; −2.18, −0.24), interleukin 6 levels (WMD: −2.41 ng/L, 95%CI; −4.35, −0.47). However, cardamom supplementation did not significantly affect systolic blood pressure. This meta-analysis demonstrated that green cardamom could improve blood pressure control and exert antiinflammatory effects which could help patients with unhealthy metabolic profile better manage their health. Importantly, there were few eligible randomized trials with quite a low number of participants. Further prospective studies on larger sample sizes and longer duration of supplementation are warranted for its widespread use.     

Extracellular flux analysis in intact cardiac tissue slices—A novel tool to investigate cardiac substrate metabolism in mouse myocardium

Aim

Cardiac pathologies are accompanied by alterations in substrate metabolism, and extracellular flux analysis is a standard tool to investigate metabolic disturbances, especially in immortalized cell lines. However, preparations of primary cells, such as adult cardiomyocytes require enzymatic dissociation and cultivation affecting metabolism. Therefore, we developed a flux analyzer-based method for the assessment of substrate metabolism in intact vibratome-sliced mouse heart tissue.

Methods

Oxygen consumption rates were determined using a Seahorse XFe24-analyzer and “islet capture plates.” We demonstrate that tissue slices are suitable for extracellular flux analysis and metabolize both free fatty acids (FFA) and glucose/glutamine. Functional integrity of tissue slices was proven by optical mapping-based assessment of action potentials. In a proof-of-principle approach, the sensitivity of the method was tested by analyzing substrate metabolism in the remote myocardium after myocardial infarction (I/R).

Results

Here, I/R increased uncoupled OCR compared with sham animals indicating a stimulated metabolic capacity. This increase was caused by a higher glucose/glutamine metabolism, whereas FFA oxidation was unchanged.

Conclusion

In conclusion, we describe a novel method to analyze cardiac substrate metabolism in intact cardiac tissue slices by extracellular flux analysis. The proof-of-principle experiment demonstrated that this approach has a sensitivity allowing the investigation of pathophysiologically relevant disturbances in cardiac substrate metabolism.