N-hydroxy-pyrroline modification of verapamil exhibits antioxidant protection of the heart against ischemia/reperfusion-induced cardiac dysfunction without compromising its calcium antagonistic activity

Any clinical intervention (e.g., coronary angioplasty, thrombolysis) used to reintroduce blood flow to an ischemic region of the myocardium is accompanied by a complex enzymatic cascade of reactions resulting in severe injury to the heart, termed myocardial ischemia/reperfusion (I/R) injury. In this study, we evaluated the ability of H-3010 (1-hydroxy-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrole-3-carboxylic acid (2-(3,4-dimethoxyphenyl)-5-([2-(3,4-dimethoxyphenyl)ethyl]-methylamino)-2-isopropylpentyl)-amide), a pyrroline modification of verapamil (2-(3,4-dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethylmethyl-amino]-2-(1-methylethyl)pentanenitrile), to protect the heart against I/R-mediated injury. Isolated perfused rat hearts pretreated with verapamil and H-3010 were subjected to 30 min of global no-flow ischemia followed by 45 min of reperfusion. The recovery (expressed as a percentage of preischemic baseline) in contractile function (left ventricular developed pressure) of hearts subjected to I/R was significantly higher in hearts treated with H-3010 at 5 microM (51.0 +/- 6.4%) as well as at 50 microM (75.1 +/- 7.4%) as compared with verapamil at 5 microM (32.2 +/- 3.7%) or untreated control hearts (18.1 +/- 2.8%). Creatine kinase release was significantly attenuated in hearts treated with H-3010 (45.7 +/- 4.5 U/liter) as compared with untreated controls (131.5 +/- 6.4 U/liter). Similar trends were also observed for lactate dehydrogenase release as well. A marked reduction in percent area of infarction was observed in the H-3010 group (11.7 +/- 1.6%) compared with verapamil (25.1 +/- 2.9%) and control (41.3 +/- 1.9%) groups. Additional in vitro studies showed a marked decrease in reactive oxygen species generation with H-3010. In conclusion, our data clearly demonstrated that the verapamil derivative, H-3010, significantly decreased I/R-induced cardiac dysfunction. This can be attributed to the combined benefits of the pyrroline moiety (antioxidant) and the parent verapamil component (antiarrhythmic) in the protection of the heart from I/R-induced injury.     

Case report of a uniocular topography guided laser-assisted in situ keratomileusis enhancement following an incorrectly treated astigmatic axis

A 23-year-old male presented to us wanting spectacle removal for cosmetic purposes. He underwent bilateral wavefront optimized (WFO) laser-assisted in situ keratomileusis (LASIK) on the Alcon Wavelight^® EX-500 excimer laser with an incorrectly treated astigmatism axis for left eye due to a manual data entry error in the laser. WFO LASIK treats the sphere and cylinder only. LASIK enhancement with topographic-guided ablation resulted in the elimination of all refractive errors and gave excellent results. Wavelight^® topographic-guided treatment can perform two separate layers of correction in the same ablation: The first is to treat the corneal irregularities for the higher order aberration (HOA) removal, the second one meant to treat the sphere and cylinder if indicated.     

Extent of re-excision,sequence/timing of salvage re-irradiation,and disease-free interval impact upon clinical outcomes in recurrent/progressive ependymoma

Journal of Neuro-Oncology - To report clinical outcomes of salvage re-irradiation (re-RT) in recurrent/progressive ependymoma. Medical records of patients treated with curative-intent re-RT as...     

True thymic hyperplasia causing pure red cell aplasia: a case report

Pure red cell aplasia caused by true thymic hyperplasia is extremely rare. We report the case of a 25-year-old female diagnosed with pure red cell aplasia. Following a thymectomy confirming true thymic hyperplasia and corticosteroid therapy, complete response was achieved. Patients diagnosed with pure red cell aplasia should be investigated with a computerized tomographic scan to assess for thymic pathology and if present, this should be resected. Follow-up is essential to monitor for recurrence.     

Non-destructive measurement technique for water content in organic solvents based on a thermal approach

The water content of organic solvents is one of the crucial properties that affect the quality of the products and the efficiency of the manufacturing processes. The established water determination methods such as Karl Fischer titration and gas chromatography require skilled operators, specific reagents, and prolonged measurement time. Thus, they are not suitable for both on-line and in-line applications. In this study, we aim to develop a real-time and low-cost device with reliable accuracy. The proposed device based on a newly developed thermal approach could non-destructively detect the water content in multiple organic solvents at low concentrations with high accuracy and without the use of any specific reagent. Experiments were performed for the determination of water content in organic solvents such as methanol, ethanol, and isopropanol. The results show that the proposed device is feasible for the water content determination in methanol, ethanol, and isopropanol at 0–1% w/w. A Bland–Altman plot to illustrate the differences in measurements between the proposed device and coulometric Karl Fischer titration shows that most of the measurements lie within the limits of agreement where 95% of the differences between the two methods are expected to fall in the range of −0.13% and 0.09%.

The proposed device could non-destructively detect the water content in organic solvents at low concentrations with high accuracy and without any specific reagent. It could determine the water content in methanol, ethanol, and isopropanol at 0–1% w/w.     

Human Brain Organoids as Models for Central Nervous System Viral Infection

Pathogenesis of viral infections of the central nervous system (CNS) is poorly understood, and this is partly due to the limitations of currently used preclinical models. Brain organoid models can overcome some of these limitations, as they are generated from human derived stem cells, differentiated in three dimensions (3D), and can mimic human neurodevelopmental characteristics. Therefore, brain organoids have been increasingly used as brain models in research on various viruses, such as Zika virus, severe acute respiratory syndrome coronavirus 2, human cytomegalovirus, and herpes simplex virus. Brain organoids allow for the study of viral tropism, the effect of infection on organoid function, size, and cytoarchitecture, as well as innate immune response; therefore, they provide valuable insight into the pathogenesis of neurotropic viral infections and testing of antivirals in a physiological model. In this review, we summarize the results of studies on viral CNS infection in brain organoids, and we demonstrate the broad application and benefits of using a human 3D model in virology research. At the same time, we describe the limitations of the studies in brain organoids, such as the heterogeneity in organoid generation protocols and age at infection, which result in differences in results between studies, as well as the lack of microglia and a blood brain barrier.