Selective electrochemical determination of dopamine at p-nitroaniline film-hole modified glassy carbon electrodes

Herein, we report determination of dopamine (DA) at modified glassy carbon electrode (GCE) with a film produced by reduction of diazonium generated from p-nitroaniline (PNA). Pores were created purposely by stripping pre-deposited gold nanoparticles (AuNPs) in the modifier film. The modified electrodes were characterized electrochemically by common redox probes: hydroquinone (HQ), hexacyanoferrate [(Fe(CN)6)]3- and hexamine ruthenium(III) [Ru(NH3)6]3+. Comparison was made for the cyclic voltammetric and amperometric response of DA using the modified electrodes against the bare GCE in phosphate buffer solution (PBS) of pH 7.5. The bare and modified GCE showed a linear response to DA in the concentration range of 0.2-2.2 mM and 5-35 µM with detection limit of 0.015 mM and 0.6112 µM, respectively. The modified electrode showed high sensitivity, well selectivity, good anti-interference ability, durable stability and good electrode reproducibility for determining DA. The reported modified electrode is a promising sensor for use in electroanalysis of DA. KEY WORDS: Diazonium, p-Nitroaniline, Gold nanoparticles, Dopamine, Ascorbic acid, Glassy carbon electrode Bull. Chem. Soc. Ethiop. 2017, 31(3), 361-372DOI: http://dx.doi.org/10.4314/bcse.v31i3.

A Case of Right Ventricular Failure Secondary to Acute Chest Syndrome Managed With Early Red Cell Exchange Transfusion

Patients with sickle cell disease are at risk of vaso-occlusive crises including acute chest syndrome (ACS) and pulmonary hypertension. ACS is a life-threatening complication of sickle cell disease and is associated with increased morbidity and mortality. It is known that pulmonary pressures increase during episodes of acute chest syndrome and may lead to acute right ventricular failure leading to increased morbidity and mortality. Given the paucity of randomized controlled trials, the management of ACS and pulmonary hypertension in the setting of a sickle cell crisis largely relies on expert opinion. We present a case of acute chest syndrome complicated by acute right ventricular failure that was managed with prompt red cell exchange transfusion with favorable clinical outcomes

Relationships among the F2 to F6 generations in chickpea (Cicer arietinum L.)

An experiment was conducted to determine the relationships among the F2 to F6 generations of 9 chickpea crosses (Cicer arietinum L.). The F2 yields had a significant and positive correlation with those of the F3. The mean yields of the F2 and F3 were not associated with the mean seed yield of the F4, F5 and F6. Significant associations among the F2 to F6 were found for days to 50% flowering, days to maturity and individual seed mass. From the results, it is concluded that selection based on early generation bulk yield tests may not be effective. The observed inconsistency in performance of different generations may have been caused by genetic shift and breaking of gene linkage

Identification and Characterization of AES-135, a Hydroxamic Acid-Based HDAC Inhibitor That Prolongs Survival in an Orthotopic Mouse Model of Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, incurable cancer with a 20% 1 year survival rate. While standard-of-care therapy can prolong life in a small fraction of cases, PDAC is inherently resistant to current treatments, and novel therapies are urgently required. Histone deacetylase (HDAC) inhibitors are effective in killing pancreatic cancer cells in in vitro PDAC studies, and although there are a few clinical studies investigating combination therapy including HDAC inhibitors, no HDAC drug or combination therapy with an HDAC drug has been approved for the treatment of PDAC. We developed an inhibitor of HDACs, AES-135, that exhibits nanomolar inhibitory activity against HDAC3, HDAC6, and HDAC11 in biochemical assays. In a three-dimensional coculture model, AES-135 kills low-passage patient-derived tumor spheroids selectively over surrounding cancer-associated fibroblasts and has excellent pharmacokinetic properties in vivo. In an orthotopic murine model of pancreatic cancer, AES-135 prolongs survival significantly, therefore representing a candidate for further preclinical testing

Development of HDAC Inhibitors Exhibiting Therapeutic Potential in T-Cell Prolymphocytic Leukemia

Epigenetic targeting has emerged as an efficacious therapy for hematological cancers. The rare and incurable T-cell prolymphocytic leukemia (T-PLL) is known for its aggressive clinical course. Current epigenetic agents such as histone deacetylase (HDAC) inhibitors are increasingly used for targeted therapy. Through a structure-activity relationship (SAR) study, we developed an HDAC6 inhibitor KT-531, which exhibited higher potency in T-PLL compared to other hematological cancers. KT-531 displayed strong HDAC6 inhibitory potency and selectivity, on-target biological activity, and a safe therapeutic window in nontransformed cell lines. In primary T-PLL patient cells, where HDAC6 was found to be overexpressed, KT-531 exhibited strong biological responses, and safety in healthy donor samples. Notably, combination studies in T-PLL patient samples demonstrated KT-531 synergizes with approved cancer drugs, bendamustine, idasanutlin, and venetoclax. Our work suggests HDAC inhibition in T-PLL could afford sufficient therapeutic windows to achieve durable remission either as standalone or in combination with targeted drugs.Peer reviewe