Utilizing single-use technology for diabetes monitoring via breath acetone

Diabetes can be a life-long disease which requires regular blood-glucose monitoring. Current technology, albeit good, does have its draw-backs; in particular that it is an invasive technique which causes discomfort to the individual. Therefore, low compliance is observed which can ultimately lead to other health issues. Approaches are underway to develop a portable, hand-held, noninvasive monitoring device to detect the biomarker, acetone, found in the breath of diabetics. By creating single-use sensor slides from polymers films of poly(4-vinylbenzeneboronic acid) and poly(allylamine hydrochloride), acetone can react with these via a Petasis reaction. Analyzing the difference in output voltage from exposed to unexposed slides at varying acetone concentrations, using a light emitting diode with a UV-photosensor and an integrated transimpedance amplifier, provides a linear relationship up to 2500 ppb, which is above the high point for breath acetone concentrations. We have engineered a hand-held breathalyzer device to detect acetone in the breath of diabetic individuals and have clinically correlated the results with blood glucose. The single-use sensor slides will ultimately provide patients with diabetes with a means of determining blood-glucose levels in a completely non-invasive manner. Please click Additional Files below to see the full abstract

Point-of-Care Diabetes Monitoring via Breath Acetone Detection

Purpose: Diabetes can be a life-long disease which requires continuous blood-glucose monitoring. Currently technology, albeit good, does have its draw-backs; in particular that it is an invasive technique which causes discomfort to the individual. Therefore, low compliance can ultimately lead to other health issues. Approaches are underway to develop a portable, hand-held, noninvasive monitoring device to detect the biomarker, acetone, found in the breath of diabetics. By creating films of poly(4-vinylbenzeneboronic acid) and poly(allylamine hydrochloride), acetone can react with these via a Petasis reaction. This alters the physicochemical nature of the film, providing a quantification of acetone, and thus hopefully blood-glucose levels, in a non-invasive manner. Methods: UV-transmitting poly(methyl methacrylate) slides are coated with a system of PAH/PVBBA at differing pH values and are then exposed to acetone/water vapor. Concentrations of acetone evaluated are 0.1–10 ppm. The slides are next subjected to the light emitted by a diode with a peak wavelength of 300 ± 5 nm. The transmitted light is detected by a UV-photosensor with an integrated transimpedance amplifier that produces a voltage output as a function of absorption. Results: We have successfully synthesized poly(4-vinylbenzeneboronic acid) and multilayered with poly(allylamine hydrochloride). We have been able to cross-link these two polymers using only acetone vapor and are developing a hand-held device. Analyzing the difference in output voltage from exposed to unexposed slides at varying acetone concentrations, provides is a linear relationship up to 2500 ppb, which is above the high point for breath acetone concentration. Conclusions: We have been able to develop a technology that accurately detects acetone vapor. We are engineering a hand-held breathalyzer device to detect acetone in the breath of diabetic individuals and are attempting to optimize its capabilities

Comparison of small molecules VEGFR inhibitors in the treatment of renal cell carcinoma

Vascular endothelial growth factors receptors (VEGFR) inhibitors play a vital role in the treatment of renal cell carcinoma. These are small molecules that predominantly exhibit anti-angiogenesis activity in conjunction with other anti-tumor effects. These drug therapies are approved for the use in patients as frontline agents or adjuvant therapy in renal cell carcinoma. However, VEGFR inhibitors are associated with undesirable adverse events, with some having a more manageable toxicity profile compared to others. As a result, choice of treatment poses a challenge for healthcare providers and patients. Nonetheless, these agents demonstrate improved disease/progression free survival (DFS/PFS) values and remain a critical component in the treatment of kidney cancer

Comparison of small molecules VEGFR inhibitors in the treatment of renal cell carcinoma

Vascular endothelial growth factors receptors (VEGFR) inhibitors play a vital role in the treatment of renal cell carcinoma. These are small molecules that predominantly exhibit anti-angiogenesis activity in conjunction with other anti-tumor effects. These drug therapies are approved for the use in patients as frontline agents or adjuvant therapy in renal cell carcinoma. However, VEGFR inhibitors are associated with undesirable adverse events, with some having a more manageable toxicity profile compared to others. As a result, choice of treatment poses a challenge for healthcare providers and patients. Nonetheless, these agents demonstrate improved disease/progression free survival (DFS/PFS) values and remain a critical component in the treatment of kidney cancer

Evaluation of a chiral cubane-based Schiff base ligand in asymmetric catalysis reactions

Recently, a novel chiral cubane-based Schiff base ligand was reported to yield modest enantioselectivity in the Henry reaction. To further explore the utility of this ligand in other asymmetric organic transformations, we evaluated its stereoselectivity in cyclopropanation and Michael addition reactions. Although there was no increase in stereocontrol, upon computational evaluation using both M06L and B3LYP calculations, it was revealed that a pseudo six-membered ring exists, through H-bonding of a cubyl hydrogen to the copper core. This decreases the steric bulk above the copper center and limits the asymmetric control with this ligand.The authors thank the Niagara University Academic Center for Integrated Science and the Rochester Academy of Science for their financial support. MLI would like to thank the Barbara S. Zimmer Memorial Research Award for financial aid. MLC gratefully acknowledges generous allocations of supercomputing time from the Australian National Computational Infrastructure, support from the Australian Research Council under its Centers of Excellence program, and an ARC Future Fellowship. RP would also like to thank Western New England University, College of Pharmacy for generous financial support

Naringenin-functionalized multi-walled carbon nanotubes: a potential approach for site-specific remote-controlled anticancer delivery for the treatment of lung cancer cells

Multi-walled carbon nanotubes functionalized with naringenin have been developed as new drug carriers to improve the performance of lung cancer treatment. The nanocarrier was characterized by Transmission Electron Microscopy (TEM), Fourier-Transform Infrared Spectroscopy (FTIR), X-ray photoelectron spectroscopy, Raman Spectroscopy, and Differential Scanning Calorimetry (DSC). Drug release rates were determined in vitro by the dialysis method. The cytotoxic profile was evaluated using the MTT assay, against a human skin cell line (hFB) as a model for normal cells, and against an adenocarcinomic human alveolar basal epithelial (A569) cell line as a lung cancer in vitro model. The results demonstrated that the functionalization of carbon nanotubes with naringenin occurred by non-covalent interactions. The release profiles demonstrated a pH-responsive behavior, showing a prolonged release in the tumor pH environment. The naringenin-functionalized carbon nanotubes showed lower cytotoxicity on non-malignant cells (hFB) than free naringenin, with an improved anticancer effect on malignant lung cells (A549) as an in vitro model of lung cancer.This work was supported by the Banco do Nordeste (grant FUNDECI/2016.0015), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe (Fapitec) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Eliana B. Souto would like to acknowledge the contributions from the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) for the projects M-ERA-NET/0004/2015-PAIRED and UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Anti-tumor efficiency of Perillylalcohol/β-Cyclodextrin inclusion complexes in a sarcoma S180-induced mice model

The low solubility and high volatility of perillyl alcohol (POH) compromise its bioavailability and potential use as chemotherapeutic drug. In this work, we have evaluated the anticancer activity of POH complexed with -cyclodextrin (-CD) using three complexation approaches. Molecular docking suggests the hydrogen-bond between POH and -cyclodextrin in molar proportion was 1:1. Thermal analysis and Fourier-transform infrared spectroscopy (FTIR) confirmed that the POH was enclosed in the -CD cavity. Also, there was a significant reduction of particle size thereof, indicating a modification of the -cyclodextrin crystals. The complexes were tested against human L929 fibroblasts after 24 h of incubation showing no signs of cytotoxicity. Concerning the histopathological results, the treatment with POH/-CD at a dose of 50 mg/kg promoted approximately 60% inhibition of tumor growth in a sarcoma S180-induced mice model and the reduction of nuclear immunoexpression of the Ki67 antigen compared to the control group. Obtained data suggest a significant reduction of cycling cells and tumor proliferation. Our results confirm that complexation of POH/-CD not only solves the problem related to the volatility of the monoterpene but also increases its efficiency as an antitumor agent.This work was supported by the Banco do Nordeste (grant FUNDECI/2016.0015), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe (Fapitec) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Eliana B. Souto would like to acknowledge the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) for the project UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Pharmacogenomics and Pediatric Asthmatic Medications

Asthma is a respiratory condition often stemming from childhood, characterized by difficulty breathing and/or chest tightness. Current treatment options for both adults and children include beta-2 agonists, inhaled corticosteroids (ICS), and leukotriene modifiers (LTM). Despite recommendations by the Global Initiative for Asthma, a substantial number of patients are unresponsive to treatment and unable to control symptoms. Pharmacogenomics have increasingly become the front line of precision medicine, especially with the recent use of candidate gene and genome- wide association studies (GWAS). Screening patients preemptively could likely decrease adverse events and therapeutic failure. However, research in asthma, specifically in pediatrics, has been low. Although numerous adult trials have evaluated the impact of pharmacogenomics and treatment response, the lack of evidence in children has hindered progress towards clinical application. This review aims to discuss the impact of genetic variability and response to asthmatic medications in the pediatric population

Drug Regimen for Patients after a Pneumonectomy

Pneumonectomy is an entire lung removal and is indicated for both malignant and benign diseases. Due to its invasiveness and postoperative complications, pneumonectomy is still associated with high mortality and morbidity. Appropriate postoperative management is crucial in pneumonectomy patients to improve quality of life and overall survival rates. Diverse drug regimens are under development to be used in adjuvant chemotherapy or to improve respiratory health after a pneumonectomy. The most common causes for a pneumonectomy are non-small cell lung cancer, malignant pleural mesothelioma, and tuberculosis; thus, an appropriate drug regimen is necessary. The uncommon incidence of pneumonectomy cases remains the major obstacle in studies of postoperative drug regimens. As the majority of current studies include post-lobectomy and post-segmentectomy patients, it is highly recommended that further research of postoperative drug regimens be focused on post-pneumonectomy patients

The Ketogenic Diet: Breath Acetone Sensing Technology

The ketogenic diet, while originally thought to treat epilepsy in children, is now used for weight loss due to increasing evidence indicating that fat is burned more rapidly when there is a low carbohydrate intake. This low carbohydrate intake can lead to elevated ketone levels in the blood and breath. Breath and blood ketones can be measured to gauge the level of ketosis and allow for adjustment of the diet to meet the user’s needs. Blood ketone levels have been historically used, but now breath acetone sensors are becoming more common due to less invasiveness and convenience. New technologies are being researched in the area of acetone sensors to capitalize on the rising popularity of the diet. Current breath acetone sensors come in the form of handheld breathalyzer devices. Technologies in development mostly consist of semiconductor metal oxides in different physio-chemical formations. These current devices and future technologies are investigated here with regard to utility and efficacy. Technologies currently in development do not have extensive testing of the selectivity of the sensors including the many compounds present in human breath. While some sensors have undergone human testing, the sample sizes are very small, and the testing was not extensive. Data regarding current devices is lacking and more research needs to be done to effectively evaluate current devices if they are to have a place as medical devices. Future technologies are very promising but are still in early development stages