In vitro antiprotozoal activity of some xanthones isolated from the roots of Andrographis paniculata

Four xanthones isolated from the roots of Andrographis paniculata were tested in vitro for antiprotozoal activity against Trypanosoma brucei brucei, Trypanosoma cruzi and Leishmania infantum. Compound TDR13011 (1,2-dihydroxy-6,8-dimethoxy-xanthone) showed good activity against T. b. brucei and L. infantum with a 50% inhibitory concentration (IC50) of 4.6 microg/ml and 8 microg/ml respectively. Xanthones from the roots of Andrographis paniculata exhibited promising anti-protozoal activity and these compounds could be chemically modified to obtain a more potent product.     

Intravitreal injection of bevacizumab combined with verteporfin photodynamic therapy for choroidal neovascularization in age-related macular degeneration

PURPOSE: To report the outcome for eyes treated with intravitreal injection of bevacizumab combined with verteporfin photodynamic therapy (PDT) for choroidal neovascularization (CNV) in age-related macular degeneration (AMD). STUDY DESIGN AND PARTICIPANTS: Interventional, consecutive, retrospective case series including 40 eyes of 40 patients with newly diagnosed juxtafoveal or subfoveal CNV secondary to AMD. METHODS: The charts of patients treated with a 1.25-mg intravitreal injection of bevacizumab followed by PDT within a 2-week period were reviewed. Main outcome measures were visual acuity stabilization (defined as no change or a gain in visual acuity) and need for retreatment. RESULTS: Thirty-three (83%) of 40 eyes had stabilization of visual acuity. Mean improvement in visual acuity was 1.73 lines. Twenty-six eyes (65%) required only a single intravitreal injection of bevacizumab combined with PDT. Of the 23 eyes with 12 months of follow-up, 17 (74%) had stabilization of visual acuity, while 9 (40%) had improvement in visual acuity (mean, 1.22 Snellen lines). Eleven eyes (48%) required only a single combined treatment for CNV resolution at the 12-month follow-up. Fifteen (88%) of 17 eyes with only 6 months of follow-up required only a single combined treatment. There were no complications such as endophthalmitis, uveitis, or ocular hypertension. CONCLUSION: These findings suggest that eyes treated with both intravitreal injection of bevacizumab and PDT require none to a minimal number of re-treatments to have stabilization of vision, even at 12 months of follow-up. Further investigation with large controlled trials is warranted to outline the appropriate treatment paradigm for combination therapy.     

Synthesis of 2‐(2‐oxo‐2H‐chromen‐4‐yl)acetamides as potent acetylcholinesterase inhibitors and molecular insights into binding interactions

Sixteen novel coumarin‐based compounds are reported as potent acetylcholinesterase (AChE) inhibitors. The most active compound in this series, 5a (IC₅₀ 0.04 ± 0.01 µM), noncompetitively inhibited AChE with a higher potency than tacrine and galantamine. Compounds 5d , 5j , and 5 m showed a moderate antilipid peroxidation activity. The compounds showed cytotoxicity in the same range as the standard drugs in HEK‐293 cells. Molecular docking demonstrated that 5a acted as a dual binding site inhibitor. The coumarin moiety occupied the peripheral anionic site and showed π‐π interaction with Trp278. The tertiary amino group displayed significant cation‐π interaction with Phe329. The aromatic group showed π‐π interaction with Trp83 at the catalytic anionic site. The long chain of methylene lay along the gorge interacting with Phe330 via hydrophobic interaction. Molecular docking was applied to postulate the selectivity toward AChE of 5a in comparison with donepezil and tacrine. Structural insights into the selectivity of the coumarin derivatives toward huAChE were explored by molecular docking and 3D QSAR and molecular dynamics simulation for 20 ns. ADMET analysis suggested that the 2‐(2‐oxo‐2H‐chromen‐4‐yl)acetamides showed a good pharmacokinetic profile and no hepatotoxicity. These coumarin derivatives showed high potential for further development as anti‐Alzheimer agents.     

Utilization of Construction and Demolition Mix Waste in the Fired Brick Production: The Impact on Mechanical Properties

The European Green Deal, which emphasizes zero-waste economies, and waste recycling in construction and building materials, has arisen due to significant worldwide needs for solid waste recovery and usage. This ambitious study focuses on recycling mixed construction and demolition (C&D) waste into burnt bricks and investigating the influence of firing temperature. While pursuing its objectives, this is dependent on raw material characterization and burnt-brick product quality assessment. The recycling of mixed C&D waste is explored by mixing the waste into two soil types (alluvial and laterite) in ratios ranging from 5% to 45% at three firing temperatures (700 °C, 850 °C and 900 °C). The utilization of mixed C&D waste in amounts of 10% at 700 °C and 25% at 850 °C and 900 °C fulfilled the Indian standard. Although a fire at 700 °C results in less optimal waste utilization, it is beneficial and recommended for reducing the carbon footprint and energy use. Additional mineralogical and microstructural analyzes are performed on the optimal fired samples. The study’s findings are promising for sustainable resource usage, reducing carbon footprint, and reducing waste disposal volume. This research is a big step toward the Sustainable Development Goals of the United Nations and a circular economy.     

Efficacy,safety, and quality of life of generic and innovator ibrutinib in Indian CLL patients

To report the efficacy, safety, and quality of life (QoL) on generic and innovator ibrutinib in Indian CLL patients. This was a single centre, prospective study of treatment-naive (TN), and relapsed/refractory (R/R) CLL patients receiving ibrutinib in India. The choice of innovator or generic ibrutinib was as per patient discretion. Response and adverse events were recorded as per the 2018 iwCLL guidelines and CTCAEv4.0. QoL was assessed using the EORTC QLQ-C30 and CLL17 questionnaires. A total of 32 CLL patients (TN, n = 7 and R/R, n = 25) received ibrutinib from 2016–2019. The median age was 60 years (37–84). All TN patients attained partial response without any grade 3/4 adverse events (AE). Ibrutinib was less tolerated in the R/R setting, with 52% patients developing grade 3/4 AE and required dose reduction. Eleven patients (44%) died during follow-up. Grade 3–5 infections were seen in 44% of R/R CLL patients. Generic ibrutinib (n = 8) was comparable to innovator ibrutinib (n = 17) in terms of efficacy, safety, and QoL. Ibrutinib is less well tolerated in Indian R/R CLL patients. Infections are a common cause of morbidity and mortality. This study affirms the safety and efficacy of generic ibrutinib.Electronic supplementary materialThe online version of this article (10.1007/s12288-020-01378-6) contains supplementary material, which is available to authorized users.     

Cybersecurity for Cardiac Implantable Electronic Devices: What Should You Know?

Medical devices have been targets of hacking for over a decade, and this cybersecurity issue has affected many types of medical devices. Lately, the potential for hacking of cardiac devices (pacemakers and defibrillators) claimed the attention of the media, patients, and health care providers. This is a burgeoning problem that our newly electronically connected world faces. In this paper from the Electrophysiology Section Council, we briefly discuss various aspects of this relatively new threat in light of recent incidents involving the potential for hacking of cardiac devices. We explore the possible risks for the patients and the effect of device reconfiguration in an attempt to thwart cybersecurity threats. We provide an outline of what can be done to improve cybersecurity from the standpoint of the manufacturer, government, professional societies, physician, and patient.     

Amelioration of Endotoxin-Induced Uveitis in Rabbit by Topical Administration of Tacrolimus Proglycosome Nano-Vesicles

This work was aimed to improve the efficacy of tacrolimus in the treatment of endotoxin-induced uveitis (EIU) using propylene glycol modified lipid vesicles termed as proglycosome nano-vesicles (PNVs). PNVs were prepared by modified film hydration method. Experimental uveitis in rabbit eye was induced by an intravitreal injection of 20 μL of the endotoxin solution containing 100 ng of lipopolysaccharide endotoxin. In vivo efficacy of PNVs was determined by studying clinical symptoms of uveitis using slit lamp examination and by quantitatively measuring levels of tumor necrosis factor-alpha, interleukin-6, leukocytes and total proteins in aqueous humor, 24 h after intravitreal injection of endotoxin. Comparison was made with healthy, untreated and tacrolimus solution treated eyes. PNVs developed were nano-sized, deformable and showed sustained release of tacrolimus over period of 12 h. In vivo results indicated statistically significant difference between the effects of PNVs in the treatment of EIU compared to tacrolimus. PNV treatment not only subsides clinical symptoms of uveitis but also prevented breakdown of blood aqueous barrier. Tacrolimus loaded PNVs are potential new topical treatment for uveitis.